Frequency-aware optical coherence tomography image super-resolution via conditional generative adversarial neural network

Optical coherence tomography (OCT) has stimulated a wide range of medical image-based diagnosis and treatment in fields such as cardiology and ophthalmology. Such applications can be further facilitated by deep learning-based super-resolution technology, which improves the capability of resolving morphological structures. However, existing deep learning-based method only focuses on spatial distribution and disregard frequency fidelity in image reconstruction, leading to a frequency bias. To overcome this limitation, we propose a frequency-aware super-resolution framework that integrates three critical frequency-based modules (i.e., frequency transformation, frequency skip connection, and frequency alignment) and frequency-based loss function into a conditional generative adversarial network (cGAN). We conducted a large-scale quantitative study from an existing coronary OCT dataset to demonstrate the superiority of our proposed framework over existing deep learning frameworks. In addition, we confirmed the generalizability of our framework by applying it to fish corneal images and rat retinal images, demonstrating its capability to super-resolve morphological details in eye imaging.Comment: 13 pages, 7 figures, submitted to Biomedical Optics Express special issu

The development of meibomian glands in mice

PurposeThe purpose of this study was to characterize the natural history of meibomian gland morphogenesis in the mouse.MethodsEmbryonic (E) and post natal (P) C57Bl/6 mouse pups were obtained at E18.5, P0, P1, P3, P5, P8, P15, and P60. Eyelids were fixed and processed for en bloc staining with Phalloidin/DAPI to identify gland morphogenesis, or frozen for immunohistochemistry staining with Oil red O (ORO) to identify lipid and antibodies specific against peroxisome proliferator-activated receptor gamma (PPARγ) to identify meibocyte differentiation. Samples were then evaluated using a Zeiss 510 Meta laser scanning confocal microscope or Nikon epi-fluorescent microscope. Tissues from adult mice (2 month-old) were also collected for western blotting.ResultsMeibomian gland morphogenesis was first detected at E18.5 with the formation of an epithelial placode within the fused eyelid margin. Invagination of the epithelium into the eyelid was detected at P0. From P1 to P3 there was continued extension of the epithelium into the eyelid. ORO and PPARγ staining was first detected at P3, localized to the central core of the epithelial cord thus forming the presumptive ductal lumen. Ductal branching was first detected at P5 associated with acinar differentiation identified by ORO and PPARγ staining. Adult meibomian glands were observed by P15. Western blotting of meibomian gland proteins identified a 50 kDa and a 72 kDa band that stained with antibodies specific to PPARγ.ConclusionsWe have demonstrated that meibomian gland development bears distinct similarities to hair development with the formation of an epithelial placode and expression of PPARγ co-incident with lipid synthesis and meibocyte differentiation

Giant pressure-enhancement of multiferroicity in CuBr2

Type-II multiferroic materials, in which ferroelectric polarization is induced by inversion non-symmetric magnetic order, promise new and highly efficient multifunctional applications based on the mutual control of magnetic and electric properties. Although this phenomenon has to date been limited to low temperatures, here we report a giant pressure-dependence of the multiferroic critical temperature in CuBr$_2$. At 4.5 GPa, $T_\mathrm{C}$ is enhanced from 73.5 to 162 K, to our knowledge the highest value yet reported for a non-oxide type-II multiferroic. This growth shows no sign of saturating and the dielectric loss remains small under these high pressures. We establish the structure under pressure and demonstrate a 60\% increase in the two-magnon Raman energy scale up to 3.6 GPa. First-principles structural and magnetic energy calculations provide a quantitative explanation in terms of dramatically pressure-enhanced interactions between CuBr$_2$ chains. These large, pressure-tuned magnetic interactions motivate structural control in cuprous halides as a route to applied high-temperature multiferroicity.Comment: 10 pages, 6 figure

Phosphorus removal from eutrophic waters with an aluminium hybrid nanocomposite

An excess of phosphorus (P) is the most common cause of eutrophication of freshwater bodies. Thus, it is imperative to reduce the concentration of P to prevent harmful algal blooms. Moreover, recovery of P has been gaining importance because its natural source will be exhausted in the near future. Therefore, the present work investigated the removal and recovery of phosphate from water using a newly developed hybrid nanocomposite containing aluminium nanoparticles (HPN). The HPN-Pr removes 0.80 ± 0.01 mg P/g in a pH interval between 2.0 and 6.5. The adsorption mechanism was described by a Freundlich adsorption model. The material presented good selectivity for phosphate and can be regenerated using an HCl dilute solution. The factors that contribute most to the attractiveness of HPN-Pr as a phosphate sorbent are its moderate removal capacity, feasible production at industrial scale, reuse after regeneration and recovery of phosphate.The authors acknowledge the Foundation for Science and Technology (FCT) Project SFRH/BD/39085/2007 for the financial support

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an H2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis. Chen et al. show that histidine decarboxylase (Hdc) marks quiescent myeloid-biased HSCs (MB-HSCs). Daughter myeloid cells form a spatial cluster with Hdc+ MB-HSCs and secrete histamine to enforce their quiescence and protect them from depletion, following activation by a variety of physiologic insults

METABOLISM OF INTRAVENOUS METHYLNALTREXONE IN MICE, RATS, DOGS AND HUMANS

were observed in rats. Dogs produced only one metabolite, MNTX-3-glucuronide (M9). In conclusion, MNTX was not extensively metabolized in humans. Conversion to methyl-6-naltrexol isomers (M4 and M5) and MNTX-3-sulfate (M2) were the primary pathways of metabolism in humans. MNTX was metabolized to a higher extent in mice than in rats, dogs, and humans. Glucuronidation was a major metabolic pathway in mice, rats and dogs, but not in humans. Overall, the data suggested species differences in the metabolism of MNTX

Cell Therapy of Congenital Corneal Diseases with Umbilical Mesenchymal Stem Cells: Lumican Null Mice

BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need

CTCF and R-loops are boundaries of cohesin-mediated DNA looping

Cohesin and CCCTC-binding factor (CTCF) are key regulatory proteins of three-dimensional (3D) genome organization. Cohesin extrudes DNA loops that are anchored by CTCF in a polar orientation. Here, we present direct evidence that CTCF binding polarity controls cohesin-mediated DNA looping. Using single-molecule imaging, we demonstrate that a critical N-terminal motif of CTCF blocks cohesin translocation and DNA looping. The cryo-EM structure of the cohesin-CTCF complex reveals that this CTCF motif ahead of zinc fingers can only reach its binding site on the STAG1 cohesin subunit when the N terminus of CTCF faces cohesin. Remarkably, a C-terminally oriented CTCF accelerates DNA compaction by cohesin. DNA-bound Cas9 and Cas12a ribonucleoproteins are also polar cohesin barriers, indicating that stalling may be intrinsic to cohesin itself. Finally, we show that RNA-DNA hybrids (R-loops) block cohesin-mediated DNA compaction in vitro and are enriched with cohesin subunits in vivo, likely forming TAD boundaries. © 2023 Elsevier Inc.FALS

Assessing Protein Dynamics on Low-Complexity Single-Stranded DNA Curtains

Single-stranded DNA (ssDNA) is a critical intermediate in all DNA transactions. Because ssDNA is more flexible than double-stranded (ds) DNA, interactions with ssDNA-binding proteins (SSBs) may significantly compact or elongate the ssDNA molecule. Here, we develop and characterize low-complexity ssDNA curtains, a high-throughput single-molecule assay to simultaneously monitor protein binding and correlated ssDNA length changes on supported lipid bilayers. Low-complexity ssDNA is generated via rolling circle replication of short synthetic oligonucleotides, permitting control over the sequence composition and secondary structure-forming propensity. One end of the ssDNA is functionalized with a biotin, while the second is fluorescently labeled to track the overall DNA length. Arrays of ssDNA molecules are organized at microfabricated barriers for high-throughput single-molecule imaging. Using this assay, we demonstrate that <i>E. coli</i> SSB drastically and reversibly compacts ssDNA templates upon changes in NaCl concentration. We also examine the interactions between a phosphomimetic RPA and ssDNA. Our results indicate that RPA–ssDNA interactions are not significantly altered by these modifications. We anticipate that low-complexity ssDNA curtains will be broadly useful for single-molecule studies of ssDNA-binding proteins involved in DNA replication, transcription, and repair