Velocity-selective arterial spin labeling perfusion measurements in 2nd trimester human placenta with varying BMI.

INTRODUCTION: Proper placental development is crucial to fetal health but is challenging to functionally assess non-invasively and is thus poorly characterized in populations. Body mass index (BMI) has been linked with adverse outcomes, but the causative mechanism is uncertain. Velocity-selective arterial spin labeling (VS-ASL) MRI provides a method to non-invasively measure placental perfusion with robustness to confounding transit time delays. In this study, we report on the measurement of perfusion in the human placenta in early pregnancy using velocity-selective arterial spin labeling (VS-ASL) MRI, comparing non-obese and obese participants. METHODS: Participants (N = 97) undergoing routine prenatal care were recruited and imaged with structural and VS-ASL perfusion MRI at 15 and 21 weeks gestation. Resulting perfusion images were analyzed with respect to obesity based on BMI, gestational age, and the presence of adverse outcomes. RESULTS: At 15 weeks gestation BMI was not associated with placental perfusion or perfusion heterogeneity. However, at 21 weeks gestation BMI was associated with higher placental perfusion (p < 0.01) and a decrease in perfusion heterogeneity (p < 0.05). In alignment with past studies, perfusion values were also higher at 21 weeks compared to 15 weeks gestation. In a small cohort of participants with adverse outcomes, at 21 weeks lower perfusion was observed compared to participants with uncomplicated pregnancies. DISCUSSION: These results suggest low placental perfusion in the early second trimester may not be the culpable factor driving associations of obesity with adverse outcomes.

A stable, highly concentrated fluorous nanoemulsion formulation for in vivo cancer imaging via 19F-MRI.

Magnetic resonance imaging (MRI) is a routine diagnostic modality in oncology that produces excellent imaging resolution and tumor contrast without the use of ionizing radiation. However, improved contrast agents are still needed to further increase detection sensitivity and avoid toxicity/allergic reactions associated with paramagnetic metal contrast agents, which may be seen in a small percentage of the human population. Fluorine-19 (19F)-MRI is at the forefront of the developing MRI methodologies due to near-zero background signal, high natural abundance of 100%, and unambiguous signal specificity. In this study, we have developed a colloidal nanoemulsion (NE) formulation that can encapsulate high volumes of the fluorous MRI tracer, perfluoro-[15-crown-5]-ether (PFCE) (35% v/v). These nanoparticles exhibit long-term (at least 100 days) stability and high PFCE loading capacity in formulation with our semifluorinated triblock copolymer, M2F8H18. With sizes of approximately 200 nm, these NEs enable in vivo delivery and passive targeting to tumors. Our diagnostic formulation, M2F8H18/PFCE NE, yielded in vivo 19F-MR images with a high signal-to-noise ratio up to 100 in a tumor-bearing mouse model at clinically relevant scan times. M2F8H18/PFCE NE circulated stably in the vasculature, accumulated in high concentration of an estimated 4-9 × 1017 19F spins/voxel at the tumor site, and cleared from most organs over the span of 2 weeks. Uptake by the mononuclear phagocyte system to the liver and spleen was also observed, most likely due to particle size. These promising results suggest that M2F8H18/PFCE NE is a favorable 19F-MR diagnostic tracer for further development in oncological studies and potential clinical translation.

Changes in tissue sodium concentration and sodium relaxation times during the maturation of human knee cartilage: Ex vivo 23 Na MRI study at 10.5 T.

PURPOSE: To evaluate the influence of skeletal maturation on sodium (23 Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. METHODS: Twelve pediatric knee specimens were imaged with whole-body 10.5 T MRI using a density-adapted 3D radial projection sequence to evaluate 23 Na parameters: B1 + , T1 , biexponential T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1 + , relaxation, and water content. The literature-based TSC (TSCLB ) used previously published values for corrections, whereas the specimen-specific TSC (TSCSP ) used measurements from individual specimens. 23 Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23 Na parameters, TSCLB - TSCSP difference, biochemical content, and age were determined. RESULTS: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ ( T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ) decreased by 72%, and the signal fraction relaxing with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ( fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ ) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP . The TSCLB - TSCSP difference was significantly correlated with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). CONCLUSION: TSC and relaxation parameters measured with 23 Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years.

A Deep Learning-Based Radiomic Classifier for Usual Interstitial Pneumonia.

BACKGROUND: Because chest CT scan has largely supplanted surgical lung biopsy for diagnosing most cases of interstitial lung disease (ILD), tools to standardize CT scan interpretation are urgently needed. RESEARCH QUESTION: Does a deep learning (DL)-based classifier for usual interstitial pneumonia (UIP) derived using CT scan features accurately discriminate radiologist-determined visual UIP? STUDY DESIGN AND METHODS: A retrospective cohort study was performed. Chest CT scans acquired in individuals with and without ILD were drawn from a variety of public and private data sources. Using radiologist-determined visual UIP as ground truth, a convolutional neural network was used to learn discrete CT scan features of UIP, with outputs used to predict the likelihood of UIP using a linear support vector machine. Test performance characteristics were assessed in an independent performance cohort and multicenter ILD clinical cohort. Transplant-free survival was compared between UIP classification approaches using the Kaplan-Meier estimator and Cox proportional hazards regression. RESULTS: A total of 2,907 chest CT scans were included in the training (n = 1,934), validation (n = 408), and performance (n = 565) data sets. The prevalence of radiologist-determined visual UIP was 12.4% and 37.1% in the performance and ILD clinical cohorts, respectively. The DL-based UIP classifier predicted visual UIP in the performance cohort with sensitivity and specificity of 93% and 86%, respectively, and in the multicenter ILD clinical cohort with 81% and 77%, respectively. DL-based and visual UIP classification similarly discriminated survival, and outcomes were consistent among cases with positive DL-based UIP classification irrespective of visual classification. INTERPRETATION: A DL-based classifier for UIP demonstrated good test performance across a wide range of UIP prevalence and similarly discriminated survival when compared with radiologist-determined UIP. This automated tool could efficiently screen for UIP in patients undergoing chest CT scan and identify a high-risk phenotype among those with known ILD.

Controlling the Assembly of Cellulose-Based Oligosaccharides through Sequence Modifications.

Peptides and nucleic acids with programmable sequences are widely explored for the production of tunable, self-assembling functional materials. Herein we demonstrate that the primary sequence of oligosaccharides can be designed to access materials with tunable shapes and properties. Synthetic cellulose-based oligomers were assembled into 2D or 3D rod-like crystallites. Sequence modifications within the oligosaccharide core influenced the molecular packing and led to the formation of square-like assemblies based on the rare cellulose IVII allomorph. In contrast, modifications at the termini generated elongated aggregates with tunable surfaces, resulting in self-healing supramolecular hydrogels.

Efficient skin interactions of graphene derivatives: challenge, opportunity or both?

Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human skin was studied and their potential as topical delivery systems were investigated. While neutral graphene sheets showed no significant skin interaction, their positively and negatively charged counterparts interacted with the skin, remaining in the stratum corneum. This efficient skin interaction bears a warning but also suggests a new topical drug delivery strategy based on the sheets' high loading capacity and photothermal property. Therefore, the immunosuppressive drug tacrolimus was loaded onto positively and negatively charged graphene sheets, and its release measured with and without laser irradiation using liquid chromatography tandem-mass spectrometry. Laser irradiation accelerated the release of tacrolimus, due to the photothermal property of graphene sheets. In addition, graphene sheets with positive and negative surface charges were loaded with Nile red, and their ability to deliver this cargo through the skin was investigated. Graphene sheets with positive surface charge were more efficient than the negatively charged ones in enhancing Nile red penetration into the skin.

The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study.

Ceritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid membranes consisting of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in the absence and in the presence of cholesterol. For determining the membrane impact of both drugs on a molecular level, different experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches were applied. The data show that ceritinib, in contrast to imatinib, interacts more effectively with membranes significantly affecting various physico-chemical membrane parameters like membrane order and transmembrane permeation of polar solutes. The pronounced membrane impact of ceritinib can be explained by a strong affinity of the drug towards POPC which competes with the POPC-cholesterol interaction by that attenuating the ordering effect of cholesterol. The data are relevant for understanding putative toxic and cytotoxic side effects of these drugs such as the triggering of cell lysis or apoptosis.

Synthesis of two-dimensional triazine covalent organic frameworks at ambient conditions to detect and remove water pollutants.

Synthesis of fully triazine frameworks (C3N3) by metal catalyzed reactions at high temperatures results in carbonized and less-defined structures. Moreover, metal impurities affect the physicochemical, optical and electrical properties of the synthesized frameworks, dramatically. In this work, two-dimensional C3N3 (2DC3N3) has been synthesized by in situ catalyst-free copolymerization of sodium cyanide and cyanuric chloride, as cheap and commercially available precursors, at ambient conditions on gram scale. Reaction between sodium cyanide and cyanuric chloride resulted in electron-poor polyfunctional intermediates, which converted to 2DC3N3 with several hundred micrometers lateral size at ambient conditions upon [2 + 2+2] cyclotrimerization. 2DC3N3 sheets, in bulk and individually, showed strong fluorescence with 63% quantum yield and sensitive to small objects such as dyes and metal ions. The sensitivity of 2DC3N3 emission to foreign objects was used to detect low concentration of water impurities. Due to the high negative surface charge (-37.7 mV) and dispersion in aqueous solutions, they demonstrated a high potential to remove positively charged dyes from water, exemplified by excellent removal efficiency (>99%) for methylene blue. Taking advantage of the straightforward production and strong interactions with dyes and metal ions, 2DC3N3 was integrated in filters and used for the fast detection and efficient removal of water impurities.

Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors.

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC50 ) inhibitory concentration (IC50 =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.

Dual-Action Heteromultivalent Glycopolymers Stringently Block and Arrest Influenza A Virus Infection In Vitro and Ex Vivo.

Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglutination inhibition data suggest better adsorption of the heteromultivalent polymer than homomultivalent analogs onto the virus surface. Cryo-TEM images imply heteromultivalent compound-mediated virus aggregation. The optimized polymeric nanomaterial inhibits >99.9% propagation of various IAV strains 24 h postinfection in vitro at low nM concentrations and is up to 10000× more effective than the commercial zanamivir drug. In a human lung ex vivo multicyclic infection setup, the heteromultivalent polymer outperforms the commercial drug zanamivir and homomultivalent analogs or their physical mixtures. This study authenticates the translational potential of the dual-action targeting approach using small polymers for broad and high antiviral efficacy.

Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π-π interactions.

Insufficient stability of micellar drug delivery systems is still the major limitation to their systematic application in chemotherapy. This work demonstrates novel π-electron stabilized polyelectrolyte block copolymer micelles based on dendritic polyglycerolsulfate-cystamine-block-poly(4-benzoyl-1,4-oxazepan-7-one)-pyrene (dPGS-SS-POxPPh-Py) presenting a very low critical micelle concentration (CMC) of 0.3 mg L-1 (18 nM), 55-fold lower than that of conventional amphiphilic block copolymer micelles. The drug loading capacities of up to 13 wt% allow the efficient encapsulation of the chemotherapeutic Docetaxel (DTX). The spherical morphology of the micelles was proven by cryogenic electron microscopy (cryo-EM). Gaussian Analysis revealed well-defined sizes of 57 nm and 80 nm in the unloaded/loaded state, respectively. Experiments by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), fluorescence spectroscopy, and cross-polarization solid-state 13C NMR studied the π-π interactions between the core-forming block segment of dPGS-SS-POxPPh-Py and DTX. The findings point to a substantial contribution of these noncovalent interactions to the system's high stability. By confocal laser scanning microscopy (CLSM), the cellular uptake of fluorescein-labelled FITC-dPGS-SS-POxPPh-Py micelles was monitored after one day displaying the successful cell insertion of the cargo-loaded systems. To ensure the drug release in cancerous cells, the disassembly of the micellar DTX-formulations was achieved by reductive and enzymatic degradation studied by light scattering and GPC experiments. Further, no size increase nor disassembly in the presence of human serum proteins after four days was detected. The precise in vitro drug release was also given by the high potency of inhibiting cancer cell growth, finding half-maximal inhibitory concentrations (IC50) efficiently reduced to 68 nM coming along with high viabilities of the empty polymer materials tested on tumor-derived HeLa, A549, and McF-7 cell lines after two days. This study highlights the substantial potential of micelles tailored through the combination of π-electron stabilization with dendritic polyglycerolsulfate for targeted drug delivery systems, enabling them to have a significant foothold in the clinical treatment of cancer.

Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants.

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C60 fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously.

Evaluation of lesion and overlying articular cartilage in patients with juvenile osteochondritis dissecans of the knee using quantitative diffusion MRI.

Current clinical MRI of patients with juvenile osteochondritis dissecans (JOCD) is limited by the low reproducibility of lesion instability evaluation and inability to predict which lesions will heal after nonoperative treatment and which will later require surgery. The aim of this study is to verify the ability of apparent diffusion coefficient (ADC) to detect differences in lesion microstructure between different JOCD stages, treatment groups, and healthy, unaffected contralateral knees. Pediatric patients with JOCD received quantitative diffusion MRI between January 2016 and September 2020 in this prospective research study. A disease stage (I-IV) and stability of each JOCD lesion was evaluated. ADCs were calculated in progeny lesion, interface, parent bone, cartilage overlying lesion, control bone, and control cartilage regions. ADC differences were evaluated using linear mixed models with Bonferroni correction. Evaluated were 30 patients (mean age, 13 years; 21 males), with 40 JOCD-affected and 12 healthy knees. Nine patients received surgical treatment after MRI. Negative Spearman rank correlations were found between ADCs and JOCD stage in the progeny lesion (ρ = -0.572; p < 0.001), interface (ρ = -0.324; p = 0.041), and parent bone (ρ = -0.610; p < 0.001), demonstrating the sensitivity of ADC to microstructural differences in lesions at different JOCD stages. We observed a significant increase in the interface ADCs (p = 0.007) between operative (mean [95% CI] = 1.79 [1.56-2.01] × 10-3 mm2 /s) and nonoperative group (1.27 [0.98-1.57] × 10-3 mm2 /s). Quantitative diffusion MRI detects microstructural differences in lesions at different stages of JOCD progression towards healing and reveals differences between patients assigned for operative versus nonoperative treatment.

A New Support Film for Cryo Electron Microscopy Protein Structure Analysis Based on Covalently Functionalized Graphene.

Protein adsorption at the air-water interface is a serious problem in cryogenic electron microscopy (cryoEM) as it restricts particle orientations in the vitrified ice-film and promotes protein denaturation. To address this issue, the preparation of a graphene-based modified support film for coverage of conventional holey carbon transmission electron microscopy (TEM) grids is presented. The chemical modification of graphene sheets enables the universal covalent anchoring of unmodified proteins via inherent surface-exposed lysine or cysteine residues in a one-step reaction. Langmuir-Blodgett (LB) trough approach is applied for deposition of functionalized graphene sheets onto commercially available holey carbon TEM grids. The application of the modified TEM grids in single particle analysis (SPA) shows high protein binding to the surface of the graphene-based support film. Suitability for high resolution structure determination is confirmed by SPA of apoferritin. Prevention of protein denaturation at the air-water interface and improvement of particle orientations is shown using human 20S proteasome, demonstrating the potential of the support film for structural biology.

Ferumoxytol dynamic contrast enhanced magnetic resonance imaging identifies altered placental cotyledon perfusion in rhesus macaques†.

Identification of placental dysfunction in early pregnancy with noninvasive imaging could be a valuable tool for assessing maternal and fetal risk. Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) can be a powerful tool for interrogating placenta health. After inoculation with Zika virus or sham inoculation at gestation age (GA) 45 or 55 days, animals were imaged up to three times at GA65, GA100, and GA145. DCE MRI images were acquired at all imaging sessions using ferumoxytol, an iron nanoparticle-based contrast agent, and analyzed for placental intervillous blood flow, number of perfusion domains, and perfusion domain volume. Cesarean section was performed at GA155, and the placenta was photographed and dissected for histopathology. Photographs were used to align cotyledons with estimated perfusion domains from MRI, allowing comparison of estimated cotyledon volume to pathology. Monkeys were separated into high and low pathology groups based on the average number of pathologies present in the placenta. Perfusion domain flow, volume, and number increased through gestation, and total blood flow increased with gestation for both low pathology and high pathology groups. A statistically significant decrease in perfusion domain volume associated with pathology was detected at all gestational ages. Individual perfusion domain flow comparisons demonstrated a statistically significant decrease with pathology at GA100 and GA145, but not GA65. Since ferumoxytol is currently used to treat anemia during human pregnancy and as an off-label MRI contrast agent, future transition of this work to human pregnancy may be possible.

Design and Functional Analysis of Heterobifunctional Multivalent Phage Capsid Inhibitors Blocking the Entry of Influenza Virus.

Multiple conjugation of virus-binding ligands to multivalent carriers is a prominent strategy to construct highly affine virus binders for the inhibition of viral entry into host cells. In a previous study, we introduced rationally designed sialic acid conjugates of bacteriophages (Qß) that match the triangular binding site geometry on hemagglutinin spike proteins of influenza A virions, resulting in effective infection inhibition in vitro and in vivo. In this work, we demonstrate that even partially sialylated Qß conjugates retain the inhibitory effect despite reduced activity. These observations not only support the importance of trivalent binding events in preserving high affinity, as supported by computational modeling, but also allow us to construct heterobifunctional modalities. Capsids carrying two different sialic acid ligand-linker structures showed higher viral inhibition than their monofunctional counterparts. Furthermore, capsids carrying a fluorescent dye in addition to sialic acid ligands were used to track their interaction with cells. These findings support exploring broader applications as multivalent inhibitors in the future.

Structural and functional analysis of the roles of influenza C virus membrane proteins in assembly and budding.

Assembly and budding of the influenza C virus is mediated by three membrane proteins: the hemagglutinin-esterase-fusion glycoprotein (HEF), the matrix protein (CM1), and the ion channel (CM2). Here we investigated whether the formation of the hexagonal HEF arrangement, a distinctive feature of influenza C virions is important for virus budding. We used super resolution microscopy and found 250-nm sized HEF clusters at the plasma membrane of transfected cells, which were insensitive to cholesterol extraction and cytochalasin treatment. Overexpression of either CM1, CM2, or HEF caused the release of membrane-enveloped particles. Cryo-electron microscopy of the latter revealed spherical vesicles exhibiting the hexagonal HEF clusters. We subsequently used reverse genetics to identify elements in HEF required for this clustering. We found that deletion of the short cytoplasmic tail of HEF reduced virus titer and hexagonal HEF arrays, suggesting that an interaction with CM1 stabilizes the HEF clusters. In addition, we substituted amino acids at the surface of the closed HEF conformation and identified specific mutations that prevented virus rescue, others reduced virus titers and the number of HEF clusters in virions. Finally, mutation of two regions that mediate contacts between trimers in the in-situ structure of HEF was shown to prevent rescue of infectious virus particles. Mutations at residues thought to mediate lateral interactions were revealed to promote intracellular trafficking defects. Taken together, we propose that lateral interactions between the ectodomains of HEF trimers are a driving force for virus budding, although CM2 and CM1 also play important roles in this process.

A Nanohook-Equipped Bionanocatalyst for Localized Near-Infrared-Enhanced Catalytic Bacterial Disinfection.

Novel bionanocatalysts have opened a new era in fighting multidrug-resistant (MDR) bacteria. They can kill bacteria by elevating the level of reactive oxygen species (ROS) in the presence of chemicals like H2 O2 . However, ROSs' ultrashort diffusion distance limit their bactericidal activity. We present a nanohook-equipped bionanocatalyst (Ni@Co-NC) with bacterial binding ability that shows robust ROS-generating capacity under physiological H2 O2 levels. The Ni@Co-NC's pH-dependent performance confines its effects to the biofilm microenvironment, leaving healthy tissue unaffected. Furthermore, it can generate heat upon NIR laser irradiation, enhancing its catalytic performance while achieving heat ablation against bacteria. With the Ni@Co-NC's synergistic effects, bacterial populations fall by >99.99 %. More surprisingly, the mature biofilm shows no recurrence after treatment with the Ni@Co-NC, demonstrating its tremendous potential for treating MDR bacterial related infections.

Compositional evaluation of lesion and parent bone in patients with juvenile osteochondritis dissecans of the knee using T2 * mapping.

Juvenile osteochondritis dissecans (JOCD) lesions contain cartilaginous, fibrous and osseous tissues which are difficult to distinguish with clinical, morphological magnetic resonance imaging (MRI). Quantitative T2 * mapping has earlier been used to evaluate microstructure and composition of all aforementioned tissues as well as bone mineral density. However, the ability of T2 * mapping to detect changes in tissue composition between different JOCD lesion regions, different disease stages, and between stable and unstable lesions has not been demonstrated. This study analyzed morphological and T2 * MRI data from 25 patients (median age, 12.1 years) with 34 JOCD-affected and 13 healthy knees. Each lesion was assigned a stage reflecting the natural history of JOCD, with stages I and IV representing early and healed lesion, respectively. T2 * values were evaluated within the progeny lesion, interface and parent bone of each lesion and in the control bone region. T2 * was negatively correlated with JOCD stage in progeny lesion (ρ = -0.871; p < 0.001) and interface regions (ρ = -0.649; p < 0.001). Stage IV progeny showed significantly lower T2 * than control bone (p = 0.028). T2 * was significantly lower in parent bone than in control bone of patients with stable lesions (p = 0.009), but not in patients with unstable lesions (p = 0.14). Clinical significance: T2 * mapping enables differentiation between different stages of JOCD and quantitative measurement of the ossification degree in progeny lesion and interface. The observed T2 * decrease in healed and stable lesions may indicate increased bone density as a result of the active repair process. T2 * mapping provides quantitative information about JOCD lesion composition.

Detection and viability of murine NK cells in vivo in a lymphoma model using fluorine-19 MRI.

Natural killer (NK) cell therapies are being increasingly used as an adoptive cell therapy for cancer because they can recognize tumor cells in an antigen-independent manner. While promising, the understanding of NK cell persistence, particularly within a harsh tumor microenvironment, is limited. Fluorine-19 (19 F) MRI is a noninvasive imaging modality that has shown promise in longitudinally tracking cell populations in vivo; however, it has not been studied on murine NK cells. In this study, the impact of 19 F labeling on murine NK cell viability and function was assessed in vitro and then used to quantify NK cell persistence in vivo. While there was no noticeable impact on viability, labeling NK cells with 19 F did attenuate cytotoxicity against lymphoma cells in vitro. Fluorescent microscopy verified 19 F labeling in both the cytoplasm and nucleus of NK cells. Lymphoma-bearing mice were given intratumoral injections of 19 F-labeled NK cells in which signal was detectable across the 6 day observation period via 19 F MRI. Quantification from the composite images detected 78-94% of the initially injected NK cells across 6 days, with a significant decrease between Days 3 and 6. Postmortem flow cytometry demonstrated retention of 19 F intracellularly within adoptively transferred NK cells with less than 1% of 19 F-containing cells identified as tumor-associated macrophages that presumably ingested nonviable NK cells. This work demonstrates that 19 F MRI offers a specific imaging platform to track and quantify murine NK cells within tumors noninvasively.