Luminal Layer Research Articles

Esophageal submucosal gland duct adenoma: An unrecognised esophageal counterpart of minor salivary gland tumours with frequent BRAF V600E mutations.

Esophageal submucosal gland duct adenoma is an extremely rare benign tumour, with only a few reported cases. We conducted the largest single-centre clinical study of esophageal submucosal gland duct adenoma, examining its molecular mechanisms and clinicopathological features. Between 2018 and 2023, seven cases of esophageal submucosal gland duct adenoma were identified at a tertiary medical centre; two were female and five were male, aged between 51 and 75 years (mean = 63.8 years). Comprehensive evaluations of clinicopathological, immunohistochemical and molecular characteristics were conducted. Histologically, tumours showed papillotubular and cystic patterns lined with double layers of cells arranged in ducts, papillary folds and microcysts. The inner luminal tall columnar cells had eosinophilic cytoplasm and did not show mucin production and the basal cells showed myoepithelial differentiation. Immunohistochemically, inner luminal layer cells were positive for CK7, CK19 and CK5/6 and outer basal layer cells were positive for SMA and P40. Both layers were negative for CK20, CDX2, MUC5AC, MUC6, MUC2, GCDFP15 and Alcian blue-periodic acid-Schiff (AB-PAS). Genomic analyses revealed the presence of BRAF V600E mutations in five of seven tumours (71.43%). This study delineates a distinct subtype of benign adenoma arising from the esophageal submucosal gland duct, characterised by multiple lobulated cystic proliferation of benign epithelial layers within the submucosa. BRAF V600E mutations were present, similar to in sialadenoma papilliferum. We determined the genetic mutation present in esophageal submucosal gland duct adenoma, providing further evidence that it is an esophageal counterpart of minor salivary gland tumours.

Plasmonic Modulation of Gold Nanoplates on Multiwavelength Emission.

Plasmonic regulation introduced by metallic nanoparticles is a useful method to improve the detection performance of plasmon-based systems. Herein, we observed a unique enhancement of surface plasmon-coupled emission (SPCE) using plate-shaped plasmonic nanostructures. By assembling Au nanoplates (Au NPLs) via electrostatic adsorption between the Au nanofilm and the quantum dot (QD) layer (630 nm), the fluorescence signal of SPCE was enhanced 90 times more than that of normal SPCE after the conditions were optimized. This enhancement was mainly induced by the intense localized electromagnetic field at the tip of Au NPLs and a novel plasmonic distribution around the "hot-spot" structure between the nanoparticle and Au nanofilm. These effectively mitigated the inherent signal quenching of SPCE and enhanced the emission signal of ultrathin samples on the surface of the NPL-modified Au nanofilm structure. This strategy can be used to improve the detection sensitivity and information integrity of SPCE-based biosensing and bioimaging systems containing ultrathin luminous layers. The different enhancement efficiencies for multiwavelengths were successfully obtained through various emission angles in light of the wavelength resolution of SPCE, thus verifying the existence and importance of energy-matching coupling, and the emission for the fluorophore with low excitation efficiency could also be detected. Benefiting from this, the Au NPL-modulated SPCE system could be a candidate for simultaneous multiwavelength enhancement and high-throughput detection in multicomponent analysis.

Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases.

Glycan structures of glycoproteins and glycolipids on the surface glycocalyx and luminal sugar layers of intracellular membrane compartments in human cells constitute a key interface between intracellular biological processes and external environments. Sialic acids, a class of alpha-keto acid sugars with a nine-carbon backbone, are frequently found as the terminal residues of these glycoconjugates, forming the critical components of these sugar layers. Changes in the status and content of cellular sialic acids are closely linked to many human diseases such as cancer, cardiovascular, neurological, inflammatory, infectious, and lysosomal storage diseases. The molecular machineries responsible for the biosynthesis of the sialylated glycans, along with their biological interacting partners, are important therapeutic strategies and targets for drug development. The purpose of this article is to comprehensively review the recent literature and provide new scientific insights into the mechanisms and therapeutic implications of sialylation in glycoproteins and glycolipids across various human diseases. Recent advances in the clinical developments of sialic acid-related therapies are also summarized and discussed.

Lighting Design for Lanna Buddhist Architecture: A Case Study of Suan Dok Temple, Chiang Mai, Thailand

In Chiang Mai, Thailand, there has been an increasing demand for lighting design strategies that enhance tangible and intangible values of cultural heritage destinations. This research explores the role of lighting design in enhancing the cultural experiences and promoting the cultural tourism of Lanna Buddhist architecture. Suan Dok Temple was selected as a case study due to its historical, social, and cultural significance. This research uses qualitative approaches such as field surveys, photographic documentation, and interviews with temple authorities, cultural heritage experts and tourism professionals for the formulation of initial users’ requirements and lighting design criteria and concept. Data analysis suggested that cultural heritage and conservation, cultural tourism management, and operation and maintenance are important factors in heritage lighting design for cultural tourism. Realistic rendering images of lighting design scenes for the temple’s chedis and vihara are generated based on the concept of luminance layers representing the Buddhist cosmology idea. In addition, lighting operation and installation details are developed and presented to stakeholders for discussion on contextual and operational appropriateness. Finally, the study discusses critical lighting design factors for the development of lighting design solutions for heritage sites, particularly Lanna Buddhist temples, contributing to sustainable cultural tourism.

Investigations of Laser-Assisted Renal Denervation for Treatment of Resistant Hypertension.

Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions. For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage. The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4). The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model.

#457 Sparsentan has direct effects on the glomerular capillary wall to attenuate increased permeability after exposure to nephrotic syndrome plasma

Abstract Background and Aims The glomerular endothelial glycocalyx (eGlx), a luminal layer of proteoglycans, glycoproteins and glycolipids, forms the first part of the glomerular filtration barrier (GFB). Nephrotic syndrome (NS) describes a group of pathologies of the renal glomerulus that result in proteinuria and is associated with glomerular endothelial dysfunction. Current treatments are broad and non-specific. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist that has received accelerated approval in the United States for the reduction of proteinuria in adults with IgA nephropathy at high risk of disease progression. Our validated glomerular permeability assay directly measures the albumin permeability (Ps’alb)of capillary loops within individually trapped glomeruli [1]. This ex vivo assay is independent of haemodynamic factors and tubular albumin handling – factors known to affect urine protein concentrations. This work examines whether sparsentan could reduce glomerular albumin permeability in NS, by preserving the eGlx to maintain the GFB. Method Human NS plasma samples were collected under ethical consent from 3 patients that had undergone plasma exchange from periods when they were in relapse (RL), or subsequent remission (RM). Adult male Sprague Dawley rats (175–200 g) were perfused with 4% Ringer BSA solution. Glomeruli were isolated on ice by graded sieving from the cortex of each kidney. Glomeruli were incubated, in the presence of AF488-conjugated BSA (AF488-BSA, 30 μg/ml) and R18 (36.5 μg/ml), with 10% plasma from NS patients for 1 hour, and simultaneously treated with sparsentan (0.1 μM, 1 μM and 10 μM) or vehicle. The glomerular Ps’alb assay was used to measure changes in albumin permeability. We applied a fluorescence profile peak-to-peak confocal imaging technique to treated glomeruli to assess glomerular eGlx thickness [2]. Results Human NS patients in RL had a significantly greater proteinuria compared to RM (RL, 10, 000 ± 1, 354 mg/g; RM, 95.3 ± 59.7 mg/g, P = 0.017). Incubation of rat glomeruli with RL plasma induced a significant increase in Ps’alb (RM+vehicle, 6.0 × 10−7 ± 0.12 × 10−7 cm/s; RL+vehicle, 10.9 × 10−7 ± 0.84 × 10−7 cm/s, P < .001) with a significant reduction in glomerular eGlx thickness (RM+vehicle, 210 ± 21.2 nm; RL+vehicle, 109 ± 7.9 nm, P = .027), compared to rat glomeruli incubated with paired RM plasma. Sparsentan-treated RL incubated glomeruli were protected from both the increase in Ps’alb (RL+spars 10 µM, 6.3 × 10−7 ± 0.19 × 10−7 cm/s, P < .001) and the loss in glomerular eGlx (RL+spars 10 µM, 222 ± 8.5 nm, P = .013), to a level comparable to RM incubated glomeruli. The effect of sparsentan on Ps’alb was dose dependent (RL+spars 1 µM, 8.0 × 10−7 ± 0.46 × 10−7 cm/s; RL+spars 0.1 µM, 9.6 × 10−7 ± 0.22 × 10−7 cm/s) with Ps’alb changes correlating inversely with glomerular eGlx thickness (r² = 0.75, P < .0001). In RM glomeruli, sparsentan alone had no effect on Ps’alb compared with vehicle (RM+spars 10 µM, 6.2 × 10−7 ± 0.25 × 10−7 cm/s, P = .590), suggesting no effect on otherwise healthy capillaries. Conclusion We have shown that dual inhibition of endothelin and angiotensin receptors, with sparsentan, preserves the glomerular eGlx resulting in normalised glomerular permeability in NS. These findings suggest that the direct action of sparsentan on the GFB could help maintain barrier integrity in NS, in particular by glycocalyx protection.

Preserving Endothelial Integrity in Human Saphenous Veins during Preparation for Coronary Bypass Surgery

Introduction: While multiple factors influence coronary artery bypass graft (CABG) success rates, preserving saphenous vein endothelium during surgery may improve patency. Standard preparations include saphenous vein preparation in heparinized saline (saline) which can result in endothelial loss and damage. Here, we investigated the impact of preparing saphenous graft vessels in heparinized patient blood (blood) versus saline. Methods: Saphenous vein tissues from a total of 23 patients undergoing CABG were split into 2 groups (1) saline and (2) heparinized patient blood. Excess tissue was fixed for analysis immediately following surgery. Level of endothelial coverage, oxidative stress marker 4-hydroxynonenal (4HNE), and oxidative stress protective marker nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated. Results: In saline patient veins, histological analysis revealed a limited luminal layer, suggesting a loss of endothelial cells (ECs). Immunofluorescent staining of EC markers vascular endothelial cadherin (VE-cadherin) and endothelial nitric oxide identified a significant improvement in EC coverage in the blood versus saline groups. Although both treatment groups expressed 4HNE to similar levels, EC blood samples expressed higher levels of NRF2. Conclusion: Our data indicate that use of heparinized patient blood helps preserve the endothelium and promotes vein graft health. This has the potential to improve long-term outcomes in patients.

Adenoid Ameloblastoma- A very rare, odontogenic tumor variant with less than 20 reported cases in the literature: Report of two cases and literature review

Abstract Introduction/Objective We describe two cases of Adenoid Ameloblastoma (AA), a very rare, hybrid variant, of two of the most common odontogenic neoplasms (Ameloblastoma and adenomatoid odontogenic tumors). AA is a benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. The lesion tends to recur, and sometimes, only correctly diagnosed after recurrence. Methods/Case Report Adenoid Ameloblastomas were identified after a review of the Temple University, Department of Pathology archive from 2012-2022. A total of four specimens (two patients) were identified. Results (if a Case Study enter NA) Case# 1 22-years-old female Biopsy Location/ size: Mandible, left, 2.1 cm. Microscopic: Neoplastic proliferation composed of odontogenic epithelium in a plexiform pattern with the formation of pseudo glandular structures of variably sized cystic spaces, the peripheral epithelial cells are palisaded with reversed polarity. The central cells have clear cytoplasm and resemble stellate reticulum with occasional tight whorls of cells noted. Hemorrhage and giant cells are present in granulation tissue. The lesion was incompletely excised. Diagnosis: Benign odontogenic tumor. Case#2 (1st occurrence): -49-years-old male -Biopsy -Location and size of lesion: Maxilla-left anterior, 0.9 cm. -Microscopic: Cyst lined by loosely arranged epithelial cells with a basal cell layer having hyperchromatic and palisaded nuclei. Knots of squamous cells are present within the cyst lining. The luminal layer is flattened to cuboidal and nonkeratinized. Duct-like openings are present within the epithelium and contain myxoid stromal tissue. Focally the epithelium extends into the connective tissue as thin anastomosing strands surround the myxoid tissue. -Diagnosis: Benign odontogenic tumor. Case#2 (2nd occurrence): -Biopsy -Diagnosis: Benign odontogenic tumor Case#2 (3rd occurrence): -Excisional biopsy -Diagnosis: AA Conclusion AA is a rare, aggressive odontogenic tumor variant with morphologic overlap with other odontogenic lesions; therefore, oral pathologists and clinicians should be familiar with this entity to achieve an accurate diagnosis and prompt management.

Intestinal Barrier Dysfunction in Inflammatory Bowel Disease: Underpinning Pathogenesis and Therapeutics.

The intestinal barrier is composed of several essential elements including luminal enzymes, bile acids, water layer, epithelial layer, and enterocyte layer. It acts as a dynamic interface between the luminal contents of food, commensal and pathogenic bacteria, and the gastrointestinal tract. The role of barrier dysfunction is of significant research interest in the development and targeted treatment of chronic inflammatory gastrointestinal conditions, such as inflammatory bowel disease. This review aims to examine the role of intestinal barrier dysfunction in the development of inflammatory bowel disease, the pathophysiology of increased barrier permeability in inflammatory bowel disease, and to explore potential treatment targets and clinical applications.

The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus.

The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may be considered as the first barrier of a tripartite blood-brain barrier (BBB) consisting of (1) ecGCx; (2) BECs; and (3) an extravascular compartment of pericytes, the extracellular matrix, and perivascular astrocytes. Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally derived leukocytes into the perivascular spaces (PVS) which result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the fifth review of a quintet series that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids, and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are increasingly being regarded as a marker of cerebrovascular and neurodegenerative pathology.

A junction-dependent mechanism drives murine mammary cell intercalation for ductal elongation.

The luminal epithelium of the mammary gland is organized into monolayers; however, it originates from multilayered terminal end buds (TEBs) during development. Although apoptosis provides a plausible mechanism for cavitation of the ductal lumen, it doesn't account for ductal elongation behind TEBs. Spatial calculations in mice suggest that most TEB cells integrate into the outermost luminal layer to generate elongation. We developed a quantitative cell culture assay that models intercalation into epithelial monolayers. We found that tight junction proteins play a key role in this process. ZO-1 puncta form at the new cellular interface and resolve into a new boundary as intercalation proceeds. Deleting ZO-1 suppresses intercalation both in culture and in cells transplanted into mammary glands via intraductal injection. Cytoskeletal rearrangements at the interface are critical for intercalation. These data identify luminal cell rearrangements necessary for mammary development and suggest a mechanism for integration of cells into an existing monolayer.

Abstract 655: Protecting The Saphenous Vein Endothelium During Bypass Surgery

Coronary artery bypass graft surgeries commonly use saphenous vein grafts to revascularize diseased coronary arteries. Despite surgical and pharmacological advancements, graft failure rates remain high. Loss of endothelial cells (EC) during saphenous vein harvest and preservation likely contributes to the high incidence of graft failure. Standard methods of saphenous vein preparation and preservation during surgery include perfusion with heparinized saline solutions, a practice known to induce EC damage. As such, improved methods of saphenous vein storage may be the key to preserving EC and reducing graft failure rates. Here, we assessed the hypothesis that maintaining saphenous veins in autologous heparinized blood would preserve EC coverage and reduce cellular damage compared to standard of care, heparinized saline. To investigate this, saphenous vein tissues from 12 patients undergoing coronary artery bypass graft surgery were split into 2 treatment groups, 1) standard maintenance in heparin-saline (n=6) and 2) maintenance in heparin-blood (n=6). At the end of the surgeries, excess saphenous vein tissues were immediately fixed in 4% PFA to analyze endothelial coverage and DNA damage. In heparin-saline veins, histological analysis by H&E and Movat pentachrome staining revealed a broken or absent luminal layer and exposed lamina matrix, suggesting a loss of endothelial cell coverage. Luminal cell coverage was notably increased in heparin-blood samples. Immunofluorescent staining of endothelial markers VE-cadherin and endothelial nitric oxide identified a significant improvement in endothelial coverage in the heparin-blood group compared to heparin-saline. To determine the health of remaining endothelial cells, DNA damage was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Our data show that most of the endothelium (VE-cadherin positive) in heparin-saline tissues was TUNEL positive compared with heparin-blood. In conclusion, our data indicate that maintaining saphenous vein tissues in solutions containing autologous heparinized blood helps preserve the endothelium and maintains vein graft health which has the potential to improve vein graft patency rates in patients.

Acral BRAF‐mutated tubular adenoma should be distinguished from HPV42‐related digital papillary adenocarcinoma

Acral <i>BRAF</i>‐mutated tubular adenoma should be distinguished from <scp>HPV42</scp>‐related digital papillary adenocarcinoma

MP34-11 URINARY GLYCOSAMINOGLYCANS ARE ASSOCIATED WITH RECURRENT UTI AND UROBIOME ECOLOGY IN POSTMENOPAUSAL WOMEN

You have accessJournal of UrologyCME1 Apr 2023MP34-11 URINARY GLYCOSAMINOGLYCANS ARE ASSOCIATED WITH RECURRENT UTI AND UROBIOME ECOLOGY IN POSTMENOPAUSAL WOMEN Michael L. Neugent, Neha V. Hulyalkar, Philippe E. Zimmern, Kelli L. Palmer, Vladimir Shulaev, and Nicole J. De Nisco Michael L. NeugentMichael L. Neugent More articles by this author , Neha V. HulyalkarNeha V. Hulyalkar More articles by this author , Philippe E. ZimmernPhilippe E. Zimmern More articles by this author , Kelli L. PalmerKelli L. Palmer More articles by this author , Vladimir ShulaevVladimir Shulaev More articles by this author , and Nicole J. De NiscoNicole J. De Nisco More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003268.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The composition of urinary glycosaminoglycans (GAGs) is not fully understood. The luminal urothelial GAG layer is likely an important interface between the human host and the resident urobiome, which has been shown to be altered in postmenopausal (PM) women with history of recurrent urinary tract infection (rUTI).1 We sought to profile the urinary GAG distribution and associate urinary GAGs with the ecology of the resident urobiome in a controlled cohort of PM women designed to study rUTI. METHODS: Clean catch midstream urine was collected from a controlled cohort of PM women (n=75) who passed a set of exclusion criteria for an ongoing study of rUTI.1 GAGs were extracted from urine via macromolecular filtration and then enzymatically digested into constituent disaccharides for chondroitin Sulfate (CS), heparin Sulfate (HS), and hyaluronic Acid (HA) following a published protocol.2 The liberated disaccharides were analyzed and quantified via targeted liquid chromatography-mass spectrometry (LC-MS/MS). For whole genome metagenomics, DNA was purified from matched urine and prepared libraries were sequenced on an Illumina NextSeq500 and analyzed for taxonomic enrichment as described previously.1 RESULTS: We find that CS is the major urinary GAG in PM women and women who were experiencing an active UTI exhibited significantly higher urinary CS compared to those with no UTI (Figure 1). Lastly, we find that two urobiome bacterial species, Atopobium vaginae and Blautia obeum exhibit significant negative associations with urinary CS. CONCLUSIONS: Our findings of increased urinary CS during active UTI may be a sign of tissue damage during infection. We find negative associations between bacterial species known to be associated with vaginal dysbiosis and urinary CS levels. These associations may be indicators of bladder dysbiosis and alterations of urothelial GAG composition.

Detailed analysis and simulation verification for reconstruction of plasma optical boundary with spectrometric technique on HL-2M tokamak

The plasma optical boundary reconstruction technique based on Hommen’s theory is promising for future tokamaks with high parameters. In this work, we conduct detailed analysis and simulation verification to estimate the ‘logic loophole’ of this technique. The finite-width effect and unpredictable errors reduce the technique’s reliability, which leads to this loophole. Based on imaging theory, the photos of a virtual camera are simulated by integrating the assumed luminous intensity of plasma. Based on Hommen’s theory, the plasma optical boundary is reconstructed from the photos. Comparing the reconstructed boundary with the one assumed, the logic loophole and its two effects are quantitatively estimated. The finite-width effect is related to the equivalent thickness of the luminous layer, which is generally about 2‒4 cm but sometimes larger. The level of unpredictable errors is around 0.65 cm. The technique based on Hommen’s theory is generally reliable, but finite-width effect and unpredictable errors have to be taken into consideration in some scenarios. The parameters of HL-2M are applied in this work.

Silver Nanoantenna Stickers for Photoluminescence Control

Nanoantenna stickers, in which the periodic array of nanoparticles is embedded in an elastomer film, can be easily attached to and detached from the surface of target materials and work as nanoantennas to control light. The stickers can be fabricated by nanoimprint lithography followed by a transfer process. While aluminum nanoantenna stickers have been prepared with poly(vinylpyrrolidone) (PVP) as the sacrificial layer that is dissolved in water during the transfer process, it has been difficult to transfer the silver nanoantenna because of the weak adhesion between silver and PVP. In this work, upon placement of a thin aluminum layer between silver and PVP, a silver nanoantenna is successfully transferred into an elastomer film. We demonstrate a photoluminescence outcoupling by placing a sticker on the luminous layer. The emission pattern is modulated both spatially and spectrally in a way defined by the nanoantenna sticker. The ability to enhance photoluminescence in the forward direction is stronger than that of the aluminum nanoantenna sticker with an identical geometry.

Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes

ABSTRACT Antidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition. We identified significant differences in gut microbiome diversity in each of the intestinal parts regarding the alpha and beta diversities. Metformin treatment altered the abundance of different genera in all studied intestinal sites, with the most pronounced effect in the small intestine, where Lactococcus increased remarkably. The abundance of Lactobacillus was substantially lower in male mice compared to female mice in all locations, in addition to an enrichment of opportunistic pathogens. Diet type and intestinal layer had significant effects on microbiome composition at each of the sites studied. We observed a different effect of metformin treatment on the analyzed subsets, indicating the multiple dimensions of metformin’s effect on the gut microbiome.

Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

The cervical epithelium undergoes changes in proliferation, differentiation, and function that are critical to ensure fertility and maintain pregnancy. Here, we identify cervical epithelial subtypes in non-pregnant, pregnant, and in labor mice using single-cell transcriptome and spatial analysis. We identify heterogeneous subpopulations of epithelia displaying spatial and temporal specificity. Notably in pregnancy, two goblet cell subtypes are present in the most luminal layers with one goblet population expanding earlier in pregnancy than the other goblet population. The goblet populations express novel protective factors and distinct mucosal networks. Single-cell analysis in a model of cervical epithelial barrier disruption indicates untimely basal cell proliferation precedes the expansion of goblet cells with diminished mucosal integrity. These data demonstrate how the cervical epithelium undergoes continuous remodeling to maintain dynamic states of homeostasis in pregnancy and labor, and provide a framework to understand perturbations in epithelial health that increase the risk of premature birth.

A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland.

The mammary gland consists of a bilayered epithelial structure with an extensively branched morphology. The majority of this epithelial tree is laid down during puberty, during which actively proliferating terminal end buds repeatedly elongate and bifurcate to form the basic structure of the ductal tree. Mammary ducts consist of a basal and luminal cell layer with a multitude of identified sub-lineages within both layers. The understanding of how these different cell lineages are cooperatively driving branching morphogenesis is a problem of crossing multiple scales, as this requires information on the macroscopic branched structure of the gland, as well as data on single-cell dynamics driving the morphogenic program. Here we describe a method to combine genetic lineage tracing with whole-gland branching analysis. Quantitative data on the global organ structure can be used to derive a model for mammary gland branching morphogenesis and provide a backbone on which the dynamics of individual cell lineages can be simulated and compared to lineage-tracing approaches. Eventually, these quantitative models and experiments allow to understand the couplings between the macroscopic shape of the mammary gland and the underlying single-cell dynamics driving branching morphogenesis.

A computational study of bio-chemo-mechanics of thrombus-laden aneurysms

The role of intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) development has been controversial for decades, yet the researchers and clinicians agree that thrombus is not an innocent bystander in disease progression. In an effort to increase our understanding of its role, in this work, we present a bio-chemo-mechanical mathematical model of thrombus-laden aneurysms. Unlike all previous finite element studies, where AAAs grow due to prescribed irreversible time-dependent elastin degradation, in this study, protein degradation depends on protease activity. Enzymes degrading collagen and elastin are believed to come from the luminal layer of intraluminal thrombus and the increasing area of chemotactic vasa vasorum in the wall. The geometrical and structural spatiotemporal changes in the aneurysmal wall at the apex and shoulder region of the thrombus-laden aneurysm are explained in detail. Furthermore, we show that later ILT formation is more perilous than its early deposition, despite lower peak protease activity and related extracellular matrix degradation. Interestingly, the radial growth rate is slightly slower for fully thrombosed AAAs compared to the partially thrombosed ones, however, their axial growth is much more pronounced. Additionally, we show that thrombus deposition greatly impacts the aneurysmal sac shape and volume.