Influence of the Dielectric Constant on the Ionic Current Rectification of Bipolar Nanopores.

In this paper, we investigate how the dielectric constant, ϵ, of an electrolyte solvent influences the current rectification characteristics of bipolar nanopores. It is well recognized that bipolar nanopores with two oppositely charged regions rectify current when exposed to an alternating electric potential difference. Here, we consider dilute electrolytes with NaCl only and with a mixture of NaCl and charged nanoparticles. These systems are studied using two levels of description, all-atom explicit water molecular dynamics (MD) simulations and coarse-grained implicit solvent MD simulations. The charge density and electric potential profiles and current-voltage relationship predicted by the implicit solvent simulations with ϵ = 11.3 show good agreement with the predictions from the explicit water simulations. Under nonequilibrium conditions, the predictions of the implicit solvent simulations with a dielectric constant closer to the one of bulk water are significantly different from the predictions obtained with the explicit water model. These findings are closely aligned with experimental data on the dielectric constant of water when confined to nanometric spaces, which suggests that ϵ decreases significantly compared to its value in the bulk. Moreover, the largest electric current rectification is observed in systems containing nanoparticles when ϵ = 78.8. Using enhanced sampling, we have shown that this larger rectification arises from the presence of a significantly deeper minimum in the free energy of the system with a larger ϵ, and when a negative voltage bias is applied. Since implicit solvent models and mean-field continuum theories are often used to design Janus membranes based on bipolar nanopores, this work highlights the importance of properly accounting for the effects of confinement on the dielectric constant of the electrolyte solvent. The results presented here indicate that the dielectric constant in implicit solvent simulations may be used as an adjustable parameter to approximately account for the effects of nanometric confinement on aqueous electrolyte solvents.

Stressed out neutrophils drive metastasis.

Stress hormones can contribute to cancer progression, but how immune cells play a role in this process is unclear. In a recent study in Cancer Cell, He et al. showed that glucocorticoids potentiate metastasis by skewing neutrophils toward pro-tumorigenic functions.

Associations between Rat Infestations and Mental Health Vary by Gender, Race, and Income in Chicago.

Rats are an understudied stressor for people in urban environments around the world but the effects may not be distributed equally among residents. In this study, we examined associations between residential rat sightings and mental health in Chicago, where rat complaints are the highest of any American city. We examined how this relationship varied by frequency of rat sightings, race, ethnicity, income, home ownership, and gender and explored potential psychosocial pathways (e.g., feelings about the home) between rat sightings and mental distress. We conducted a randomized household survey along an income gradient in 2021 and asked about depressive symptoms in the past week (i.e., Center for Epidemiologic Studies Depression scale), frequency of rat sightings in/around the home, perceptions of rats, neighborhood conditions, and socio-demographic characteristics. We used logistic regression to assess relationships among these variables for our entire sample and for specific demographics using stratified models. Respondents (n = 589; 409 complete cases) who saw rats in/around the home daily/almost daily had 5.5 times higher odds of reporting high depressive symptoms relative to respondents who saw rats less frequently after accounting for socio-demographics and neighborhood conditions. This relationship was significant for men and respondents with lower incomes or race or ethnicity other than white. Our results show that rat infestations should be considered a threat to mental health among urban residents. Increased mental health support for residents living in rat-infested housing may improve public health in cities.

Gentrification drives patterns of alpha and beta diversity in cities.

While there is increasing recognition that social processes in cities like gentrification have ecological consequences, we lack nuanced understanding of the ways gentrification affects urban biodiversity. We analyzed a large camera trap dataset of mammals (>500 g) to evaluate how gentrification impacts species richness and community composition across 23 US cities. After controlling for the negative effect of impervious cover, gentrified parts of cities had the highest mammal species richness. Change in community composition was associated with gentrification in a few cities, which were mostly located along the West Coast. At the species level, roughly half (11 of 21 mammals) had higher occupancy in gentrified parts of a city, especially when impervious cover was low. Our results indicate that the impacts of gentrification extend to nonhuman animals, which provides further evidence that some aspects of nature in cities, such as wildlife, are chronically inaccessible to marginalized human populations.

Chelation-directed interface engineering of in-place self-cleaning membranes.

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche.

Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages.

CT guided biopsy for osteodiscitis reduces cost of hospitalization in the landscape of increasing intravenous drug use: A single center retrospective analysis.

OBJECTIVE: Osteodiscitis has been demonstrated to show significant morbidity and mortality. Cultures and CT guided biopsy (CTB) are commonly used diagnosis of osteodiscitis. This study's purpose is to evaluate the cost burden of CTB and to evaluate how IVDU affects patient management in the setting of osteodiscitis. METHODS: Patients admitted for osteodiscitis from 2011-2021 were retrospectively reviewed and stratified into cohorts by CTB status. Additional cohorts were stratified by Intravenous Drug Use (IVDU). Patient demographics, total cost of hospitalization, length of hospitalization, time to biopsy, IVDU status, and other factors were recorded. T-Test, Chi-squared analysis, and ANOVA were used for statistical analysis. RESULTS: Total cost of hospitalization was recorded for 140 patients without CTB and 346 patients with CTB. Average cost of hospitalization for non-CTB was $227,317.86 compared to CTB at $119,799.20 (p < 0.001). Length of stay (LOS) was found to be 18.01 days for non-CTB and 14.07 days for CTB patients (0.00282). When stratified by days until biopsy, patients who had CTB sooner, had significantly reduced cost of hospitalization (p = 0.0003). Patients with IVDU history were significantly younger (p < 0.001) with lower BMI (p < 0.001) and a significantly different clinical profile. There was a significant difference in positive open biopsy when separated by IVDU status (p = 0.025). CONCLUSION: CTB was associated with significantly reduced cost of hospitalization and LOS compared to non-CTB. IVDU patients with osteodiscitis have significantly different clinical profiles than non-IVDU that may impact diagnosis and treatment. Further work is indicated to elucidate causes of these differences to provide high value care to patients with osteodiscitis.

Acute and Chronic Kidney Disease Worsen Outcomes in Experimental Sepsis.

BACKGROUND: Infection is a leading cause of morbidity in individuals with acute and chronic kidney disease (AKD, CKD). However, there is significant difficulty in modeling infection into an animal host with preexisting kidney disease. We report a novel method of peritoneal infection induced via cecal slurry inoculation deployed into mice with experimental aristolochic acid-induced AKD and CKD. METHODS: AKD, CKD, and paired control mice were injected with sham, low, or higher doses of donor-recipient matched cecal slurry solution. Animal survival, sepsis severity, and change in glomerular filtration rate was tracked longitudinally throughout the study. Histology for kidney injury, flow cytometry, plasma cytokines, and evidence of indirect organ injury from sepsis were also assessed. RESULTS: Infected AKD mice experienced significantly heightened sepsis severity, with 100% mortality by 24 hours after high cecal slurry doses versus no mortality in control mice. Additionally, AKD mice receiving lower cecal slurry doses developed dramatically increased pro-inflammatory cytokines and persistent cytopenias. Infected CKD mice also had worse outcomes than paired CKD-controls, though less severe than in AKD mice. Interestingly, animals with AKD had worse outcomes than mice with CKD after any cecal slurry dose or time-point after inoculation, despite higher baseline kidney function and less uremic sequela. CONCLUSIONS: These data confirm that acute bacterial infection can be modeled in animals with established kidney disease; and suggest that the clinical state of kidney disease (AKD versus CKD) may influence host susceptibility to infection more than the degree of kidney failure alone.

The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.

Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve ("unhook") ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs. Here, we use Xenopus egg extracts to investigate replication-coupled repair of plasmids engineered to contain site-specific colibactin-ICLs. We show that replication fork stalling at a colibactin-ICL leads to replisome disassembly and activation of the Fanconi anemia ICL repair pathway, which unhooks the colibactin-ICL through nucleolytic incisions. These incisions generate a DNA double-strand break intermediate in one sister chromatid, which can be repaired by homologous recombination, and a monoadduct ("ICL remnant") in the other. Our data indicate that translesion synthesis past the colibactin-ICL remnant depends on Polη and a Polκ-REV1-Polζ polymerase complex. Although translesion synthesis past colibactin-induced DNA damage is frequently error-free, it can introduce T>N point mutations that partially recapitulate the mutation signature associated with colibactin exposure in vivo. Taken together, our work provides a biochemical framework for understanding how cells tolerate a naturally-occurring and clinically-relevant ICL.

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids.

Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides 38 and 49 (13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines.

Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Protein-activated atomic layer deposition for robust crude-oil-repellent hierarchical nano-armored membranes.

Atomic layer deposition (ALD) offers unique capabilities to fabricate atomically engineered porous materials with precise pore tuning and multi-functionalization for diverse applications like advanced membrane separations towards sustainable energy-water systems. However, current ALD technique is inhibited on most non-polar polymeric membranes due to lack of accessible nucleation sites. Here, we report a facile method to efficiently promote ALD coating on hydrophobic surface of polymeric membranes via novel protein activation/sensitization. As a proof of concept, TiO2 ALD-coated membranes activated by bovine serum albumin exhibit remarkable superhydrophilicity, ultralow underwater crude oil adhesion, and robust tolerance to rigorous environments including acid, alkali, saline, and ethanol. Most importantly, excellent cyclable crude oil-in-water emulsion separation performance can be achieved. The mechanism for activation/sensitization is rooted in reactivity for a particular set of amino acids. Furthermore, the universality of protein-sensitized ALD is demonstrated using common egg white, promising numerous potential usages in biomedical engineering, environmental remediation, low-carbon manufacturing, catalysis, and beyond.

Mid-infrared supermirrors with finesse exceeding 400 000.

For trace gas sensing and precision spectroscopy, optical cavities incorporating low-loss mirrors are indispensable for path length and optical intensity enhancement. Optical interference coatings in the visible and near-infrared (NIR) spectral regions have achieved total optical losses below 2 parts per million (ppm), enabling a cavity finesse in excess of 1 million. However, such advancements have been lacking in the mid-infrared (MIR), despite substantial scientific interest. Here, we demonstrate a significant breakthrough in high-performance MIR mirrors, reporting substrate-transferred single-crystal interference coatings capable of cavity finesse values from 200 000 to 400 000 near 4.5 µm, with excess optical losses (scatter and absorption) below 5 ppm. In a first proof-of-concept demonstration, we achieve the lowest noise-equivalent absorption in a linear cavity ring-down spectrometer normalized by cavity length. This substantial improvement in performance will unlock a rich variety of MIR applications for atmospheric transport and environmental sciences, detection of fugitive emissions, process gas monitoring, breath-gas analysis, and verification of biogenic fuels and plastics.

Demineralized Bone Matrix and Fibers in Spinal Fusion.

Formation of bony fusion after arthrodesis depends on osteoinduction, osteoconduction, and osteogenesis. Traditionally, the patient's own bone, or autograft, has been used to provide biological material necessary for these steps. However, the amount of autograft obtainable is often inadequate. Modern spine surgery has adopted the use of many autograft extenders or replacements, such as demineralized bone matrix or fibers. The present article covers the history of bone grafting, the production and technical details of demineralized bone matrix, and the evidence supporting its use in spine fusions.

Understanding lifetime and dispersion of cough-emitted droplets in air.

To understand the exact transmission routes of SARS-CoV-2 and to explore effects of time, space and indoor environment on the dynamics of droplets and aerosols, rigorous testing and observation must be conducted. In the current work, the spatial and temporal dispersions of aerosol droplets from a simulated cough were comprehensively examined over a long duration (70 min). An artificial cough generator was constructed to generate reliably repeatable respiratory ejecta. The measurements were performed at different locations in front (along the axial direction and off-axis) and behind the source in a sealed experimental enclosure. Aerosols of 0.3-10 µm (around 20% of the maximum nuclei count) were shown to persist for a very long time in a still environment, and this has a substantial implication for airborne disease transmission. The experiments demonstrated that a ventilation system could reduce the total aerosol volume and the droplet lifetime significantly. To explain the experimental observations in more detail and to understand the droplet in-air behaviour at various ambient temperatures and relative humidity, numerical simulations were performed using the Eulerian-Lagrangian approach. The simulations show that many of the small droplets remain suspended in the air over time instead of falling to the ground.

Montmorillonite Membranes with Tunable Ion Transport by Controlling Interlayer Spacing.

Membranes incorporating two-dimensional (2D) materials have shown great potential for water purification and energy storage and conversion applications. Their ordered interlayer galleries can be modified for their tunable chemical and structural properties. Montmorillonite (MMT) is an earth-abundant phyllosilicate mineral that can be exfoliated into 2D flakes and reassembled into membranes. However, the poor water stability and random interlayer spacing of MMT caused by weak interlamellar interactions pose challenges for practical membrane applications. Herein, we demonstrate a facile approach to fabricating 2D MMT membranes with alkanediamines as cross-linkers. The incorporation of diamine molecules of different lengths enables controllable interlayer spacing and strengthens interlamellar connections, leading to tunable ion transport properties and boosted membrane stability in aqueous environments.

Engineering In Situ Catalytic Cleaning Membrane Via Prebiotic-Chemistry-Inspired Mineralization.

Pressure-driven membrane separation promises a sustainable energy-water nexus but is hindered by ubiquitous fouling. Natural systems evolved from prebiotic chemistry offer a glimpse of creative solutions. Herein, a prebiotic-chemistry-inspired aminomalononitrile (AMN)/Mn2+ -mediated mineralization method is reported for universally engineering a superhydrophilic hierarchical MnO2 nanocoating to endow hydrophobic polymeric membranes with exceptional catalytic cleaning ability. Green hydrogen peroxide catalytically triggered in-situ cleaning of the mineralized membrane and enabled operando flux recovery to reach 99.8%. The mineralized membrane exhibited a 9-fold higher recovery compared to the unmineralized membrane, which is attributed to active catalytic antifouling coupled with passive hydration antifouling. Electron density differences derived from the precursor interaction during mediated mineralization unveiled an electron-rich bell-like structure with an inner electron-deficient Mn core. This work paves the way to construct multifunctional engineered materials for energy-efficient water treatment as well as for diverse promising applications in catalysis, solar steam generation, biomedicine, and beyond.

Wildfire and cattle legacies on gradients of soil nitrogen underlie patterns of annual brome invasion.

Human activities are increasing wildfires and livestock activity in arid ecosystems with potential implications for the spread of invasive grasses. The objective of this study was to test whether fire history and cattle activity alter soil resource gradients, thereby affecting patterns of Bromus rubens L. (red brome) invasion. Six paired burned and unburned transect lines (1-km long) were established in the northeast Mojave Desert along the boundaries of four independent wildfire scars. At 100-m transect increment points, we measured the distance to the two nearest cowpats, and two random points and measured the density, height, biomass, and seed production of red brome, soil moisture and inorganic nitrogen (N). Cattle activity was 29% greater along burned transects compared to unburned transects (P < 0.05). Red brome height, density, and seed production were 11-34% greater along burned transects than unburned transects (P < 0.05). Red brome height, biomass, density, and seed production were twofold to tenfold greater next to cowpats compared to random points (P < 0.05). Soils along burned transects and beneath cowpats had greater soil inorganic N (P < 0.05), which was positively correlated with red brome density, height, biomass, and seed production (R2 = 0.60-0.85, P < 0.0001). Transgenerational effects were evident as seeds from red brome next to cowpats had 27% higher germination than seeds collected from random points. Positive responses of red brome to increased inorganic N related to fire and cattle activity may contribute fine fuel infill that drives invasive grass-fire cycles in deserts.