Tissue Organization Research Articles

Bone microphysiological models for biomedical research.

Bone related disorders are highly prevalent, and many of these pathologies still do not have curative and definitive treatment methods. This is due to a complex interplay of multiple factors, such as the crosstalk between different tissues and cellular components, all of which are affected by microenvironmental factors. Moreover, these bone pathologies are specific, and current treatment results vary from patient to patient owing to their intrinsic biological variability. Current approaches in drug development to deliver new drug candidates against common bone disorders, such as standard two-dimensional (2D) cell culture and animal-based studies, are now being replaced by more relevant diseases modelling, such as three-dimension (3D) cell culture and primary cells under human-focused microphysiological systems (MPS) that can resemble human physiology by mimicking 3D tissue organization and cell microenvironmental cues. In this review, various technological advancements for in vitro bone modeling are discussed, highlighting the progress in biomaterials used as extracellular matrices, stem cell biology, and primary cell culture techniques. With emphasis on examples of modeling healthy and disease-associated bone tissues, this tutorial review aims to survey current approaches of up-to-date bone-on-chips through MPS technology, with special emphasis on the scaffold and chip capabilities for mimicking the bone extracellular matrix as this is the key environment generated for cell crosstalk and interaction. The relevant bone models are studied with critical analysis of the methods employed, aiming to serve as a tool for designing new and translational approaches. Additionally, the features reported in these state-of-the-art studies will be useful for modeling bone pathophysiology, guiding future improvements in personalized bone models that can accelerate drug discovery and clinical translation.

Correction of Non-Uniform Rotational Distortion in the Proximally Controlled Endoscopic OCTA.

Endoscopic Optical Coherence Tomography (OCT) can provide high-resolution cross-sectional images for internal organ tissues. Combining the endoscopic imaging with Optical Coherence Tomography Angiography (OCTA), information of blood vessels in superficial lumen tissues is expected to be acquired. However, in endoscopic OCT systems using proximal scanning probes, performance of OCTA encounters significant challenges due to non-uniform rotational distortion (NURD) caused by the non-constant rotation of the distal imaging unit. In this study, we proposed a registration method for endoscopic OCTA imaging in a proximally controlled OCT System. Global registration and A-line registration were employed to correct the distortion caused by mechanical friction between the catheter sheath and torque coil. Experimental performances in both microfluidic channel and rat rectum show significant correction of NURD. Our study achieved the first implementation of endoscopic OCTA under a spiral B-scan rotation scheme in a proximally controlled OCT system, facilitating clear visualization of blood flow.

Spatial Patterning Analysis of Cellular Ensembles (SPACE) finds complex spatial organization at the cell and tissue levels

Spatial patterns of cells and other biological elements drive physiologic and pathologic processes within tissues. While many imaging and transcriptomic methods document tissue organization, discerning these patterns is challenging, especially when they involve multiple elements in complex arrangements. To address this challenge, we present Spatial Patterning Analysis of Cellular Ensembles (SPACE), an R package for analysis of high-plex spatial data. SPACE is compatible with any data collection modality that records values (i.e., categorical cell/structure types or quantitative expression levels) at fixed spatial coordinates (i.e., 2d pixels or 3d voxels). SPACE detects not only broad patterns of co-occurrence but also context-dependent associations, quantitative gradients and orientations, and other organizational complexities. Via a robust information theoretic framework, SPACE explores all possible ensembles of tissue elements-single elements, pairs, triplets, and so on-and ranks the most strongly patterned ensembles. For single images, rankings reflect differences from random assortment. For sets of images, rankings reflect differences across sample groups (e.g., genotypes, treatments, timepoints, etc.). Further tools then characterize the nature of each pattern for intuitive interpretation. We validate SPACE and demonstrate its advantages using murine lymph node images for which ground truth has been defined. We then detect new patterns across varied datasets, including tumors and tuberculosis granulomas.

Antibacterial UV-Curable Gel with Hydroxyapatite Nanoparticles for Regenerative Medicine in the Field of Orthopedics

The development and analysis of the properties of a new material based on UV-curable acrylate monomers with silicon-containing hydroxyapatite and zinc oxide nanoparticles as an antibacterial component and gelatin was carried out. Using this material in orthopedics and dentistry is very convenient because it covers any surface geometry of metal implants and hardens under ultraviolet light. In this work, sorption properties, changes in porosity, and mechanical properties of the material were investigated. The conditions for obtaining hydroxyapatite (HA) nanoparticles and the presence of silicon oxide nanoparticles and organic for the shell in an aqueous medium were studied for the pH of the medium, the sequence of administration and concentration of the material components, as well as antibacterial properties. This polymer material is partially resorbable. That supports not only the growth of bone cells but also serves as a protective layer. It reduces friction between organic tissues and a metal implant and can be a solution to the problem of the aseptic instability of metal implants. The material can also be used to repair damaged bones and cartilage tissues, especially in cases where the application and curing procedure is performed using laparoscopic methods. In this work, the authors propose a simple and quite cheap method for obtaining material based on photopolymerizable acrylates and natural gelatin with nanoparticles of HA, zinc oxide, and silicon oxide. The method allows one to obtain a composite material with different nanoparticles in a polymer matrix which retain the requisite properties needed such as active-sized HA, antibacterial ZnO, and structure-forming and stability-improving SiO2 nanoparticles.

Advancing plant science through precision 3D bioprinting: new tools for research and biotech applications.

The integration of 3D bioprinting into plant science and biotechnology is revolutionizing research and applications. While many high-throughput techniques have advanced plant biology, replicating the complex 3D organization and cellular environments of plant tissues remains a significant challenge. Traditional 2D culture systems fall short of capturing the necessary spatial context for accurate studies of cell behavior, gene expression, and tissue development. Additionally, the lack of precise simulation of plant microenvironments limits control over cellular interactions and responses to external stimuli. Recent advancements in 3D bioprinting address these limitations by allowing precise control over cell positioning and biomaterial arrangement, thereby better replicating natural plant environments. This enables more accurate studies of gene expression, developmental processes, and stress responses. The technology also enhances our ability to test genetic modifications and biotechnological interventions, advancing crop improvement, sustainable agriculture, and precision breeding. This review examines the current state of 3D bioprinting in plant science, discusses its limitations, and explores its potential to transform research and applications in the field.

Layer-by-Layer Nanoarchitectonics: A Method for Everything in Layered Structures

The development of functional materials and the use of nanotechnology are ongoing projects. These fields are closely linked, but there is a need to combine them more actively. Nanoarchitectonics, a concept that comes after nanotechnology, is ready to do this. Among the related research efforts, research into creating functional materials through the formation of thin layers on surfaces, molecular membranes, and multilayer structures of these materials have a lot of implications. Layered structures are especially important as a key part of nanoarchitectonics. The diversity of the components and materials used in layer-by-layer (LbL) assemblies is a notable feature. Examples of LbL assemblies introduced in this review article include quantum dots, nanoparticles, nanocrystals, nanowires, nanotubes, g-C3N4, graphene oxide, MXene, nanosheets, zeolites, nanoporous materials, sol–gel materials, layered double hydroxides, metal–organic frameworks, covalent organic frameworks, conducting polymers, dyes, DNAs, polysaccharides, nanocelluloses, peptides, proteins, lipid bilayers, photosystems, viruses, living cells, and tissues. These examples of LbL assembly show how useful and versatile it is. Finally, this review will consider future challenges in layer-by-layer nanoarchitectonics.

Exploring Uropathogenic Bacteria and Measuring Serum IL-34 and IL-35 Levels in Women Affected by Systemic Lupus Erythematosus

Systemic lupus erythematosus is an autoimmune disease occurs when the immune system mistakes self-tissue for foreign antigens, it causes organ tissue destruction in Systemic lupus erythematosus risk factors include interleukin biomarkers and urinary tract infections. The goal of this study was to identify uropathogenic bacteria in systemic lupus erythematosus patients, which is essential for avoiding serious complications. Additionally, serum levels of interleukin -34 and interleukin-35 in Systemic lupus erythematosus patients serve as a predictor biomarkers for systemic lupus erythematosus diagnosis. 65 women with systemic lupus erythematosus compare to 50 healthy controls were included in this study. Isolation and identification of uropathogenic bacteria , and use enzyme-linked immunosorbent assays to check serum levels of interleukin-34 and interleukin-35.The results revealed that E. coli accounted for 70% of the uropathogenic bacteria identified, with Proteus spp. come in second accounted 20% followed by Klebsiella spp. accounted 6%., while Enterococcus fecalis and Enterobacter spp. accounted for 2% with each. A notable rise in serum levels of IL-34 and IL-35 was observed when comparing patients with systemic lupus erythematosus illness to controls, with a P.value of less than 0.05.This study investigated that E. coli was the most frequently occurring of uropathogenic bacteria. Studies have shown higher serum levels of interleukin IL-34 and IL-35 in women with systemic lupus erythematosus.

Construction of tetrahedral mesh phantom for Chinese women of childbearing age.

Although the Boundary Representation (BREP) method creates detailed surface phantoms of Chinese women of childbearing age, these phantoms cannot be directly used in Monte Carlo simulations. They must first be converted into voxel phantoms, a process that may diminish some of the inherent advantages of the surface phantoms. Therefore, the aim of this study is to construct a tetrahedral mesh (TM) phantom of Chinese women of childbearing age based on the BREP phantom, incorporating micron-level structural refinements to certain organ tissues while maintaining the original model's structure. This TM phantom can be directly implemented into Monte Carlo codes to calculate the absorbed dose at different photon energies, demonstrating that both the structure and position of organ tissues affect the radiation dose. By achieving more accurate dose assessments, we can optimize radiation protection measures and reduce the potential risks to women of childbearing age.&#xD.

The influence of fructose on structural and metabolic features of the tooth-jaw system of rats under conditions of iodine deficiency

The aim of the study was to investigate an oxidative processes intensity and structural organisation of hard and soft periodontal tissues in rats under conditions of high-fructose diet against the background of iodine deficiency (research group) and standard diet and drinking regime (intact animals). It was found that carbohydrate metabolism was impaired in rats of the research group (glucose content increased by 63.3%, insulin – by 48.2% in blood serum, glycated haemoglobin of whole blood – by 2.1 time, HOMAIR index – by 2.1 times compared to the data in intact rats) and thyroid status (free triiodothyronine and thyroxine content in blood serum decreased by 46.8 and 42.7%, respectively, compared to the control). Under such conditions, the intensity of lipid and protein peroxidation processes in periodontal tissues increases. In particular, the accumulation of diene conjugates and products that react to thiobarbituric acid in the mucous membrane of the alveolar process (by 19.0 and 7.1 times), in the teeth pulp (by 2.2 and 6.3 times) compared to the values in intact animals was found. The activation of peroxidative destruction of proteins is confirmed by an increase in the content of all fractions of their oxidative modification in the studied tissues by 2.8-8.4 times compared to the control values. The results of the histological examination of the alveolar process indicate thinning of the periosteum, disruption of the structural organisation of osteon, reduction in the thickness of bone trabeculae (by 21.8%), optical density of the osteogenic matrix (by 8.9%), area of intertrabecular connective tissue (by 61.0%). Mucosal edema of connective tissue, accumulation of glycosaminoglycans, hypertrophy of all epithelial layers (basal, prickle, keratinized layers – by 25.5-55.9%, granular layer – by 2.3 times), changes of the microcirculatory net were observed in the mucous membrane of the alveolar process. Thus, the combination of high-fructose and iodine-deficient diets causes the development of oxidative stress and destructive changes of the dentoalveolar complex of research animals, which characterises an increase of the risks of dental pathology development.

Pilot study of response of human dental pulp to direct pulp capping with polymeric nanoparticles loaded with brazilian red propolis

Direct pulp capping helps to regenerate and repair damaged dentin, preserving tooth vitality. Despite being a widely recognized method, the authors investigated the use of a natural product with significant biological activity for this purpose. Thus, the aim of this study was to evaluate the human dental pulp response to direct pulp capping with polymeric nanoparticles loaded with Brazilian red propolis (BRP) compared to mineral trioxide aggregate (MTA). Following the synthesis, the nanoparticles loaded with 50μg of BRP (NPP50) and 100μg of BRP (NPP100) were analyzed by infrared spectroscopy (FTIR) and the cytotoxicity of all materials was tested. The dental pulp of 60 healthy third molars was mechanically exposed. Then, the teeth were pulp-capped with NPP50; NPP100; MTA + NPP50; MTA + NPP100; pure MTA (control). After experimental periods (15, 45, and 60 days) the teeth were extracted and processed for histological analysis. Inflammatory cell response, pulp tissue organization, hard tissue formation and the presence of bacteria was accessed. Data were analyzed by one-way ANOVA followed by Dunnett’s post-hoc test (cytotoxicity) or Kruskal-Wallis’ test followed by Kruskal-Wallis multiple comparison test (a = 0.05). FTIR spectra of nanoparticles showed typical bands of major compounds present in BRP. All materials exhibited no-cytotoxicity. Regarding inflammatory pulp response and organization of the pulp tissue, there was no significant difference between the materials in any of the periods of evaluation (p>0.05). The direct pulp capping agents containing BRP induced mineralized tissue formation like MTA with no cytotoxicity indicating promising regenerative potential for dental pulp tissue.

Numerical and computational fluid dynamics experimental analysis of novel extended tetra-hybrid Tiwari and Das Sisko nanofluid passed a stenosed artery

The medical industry extensively uses nanoparticles for applications such as wound dressing, artificial organ components, drug delivery, tissue engineering, and cardiovascular disease treatment. The incorporation of nanoparticles into the base fluid enhances the rate of heat transmission and additionally decreases blood pressure. This study aims to examine the effects of a new tetra-hybrid nanofluid model, which includes nanoparticles, on the flow of blood through a stenosed artery with a circular shape. Model partial differential equations (PDEs) incorporate phenomena such as thermal radiation and viscous dissipation. Furthermore, we transform these modeled PDEs into dimensionless ordinary differential equations (ODEs) using self-similarity variables and numerically solve the proposed ODEs using the well-established Lobatto IIIa numerical technique. The impact of several dimensionless parameters on the heat transfer rate, skin friction, velocity, and temperature fields has been computed and analyzed using figures and tables. Moreover, we conducted a computational fluid dynamics (CFD) investigation on a tetra-hybrid nanofluid, using blood as the base fluid. The results indicate that heat transmission is higher in tetra-hybrid nanoparticles compared to tri-hybrid and di-hybrid nanofluids. The volume fraction of nanoparticles in the base fluid increases, resulting in a decrease in the surface drag coefficient and a decrease in the heat transport phenomenon. Amplification in the thermal radiation parameter improves heat transfer, helping to remove toxins and plaque from blood flowing through arteries. An increase in thermal radiation generates excess heat that dilates inflexible arteries, facilitating blood flow. From CFD analysis, it is observed that thermal conduction k and heat transfer coefficient h amplify by improving Reynolds number. Pressure at the outlet interface of the tube decreases from 3058 Pa to 2996 Pa for the case of a 10% volume fraction of nanoparticles. Velocity boundary layer thickness decreases from 1.46 to 1.37 with an increase in the volume fraction of nanoparticles from 1% to 10%. Heat deliverance rate amplifies in the case of tetrahybrid nanofluid 2.5394–2.6147 in contrast to trihybrid nanofluid 2.4008 to 2.4711 by amplifying Rd from 0.7 to 1.1. The surface drag coefficient amplifies by magnifying Re but the Nusselt number diminishes by improving the volume fraction of nanoparticles.

BSP promotes skin wound healing by regulating the expression level of SCEL.

Burn injuries are complex, life-threatening events involving intricate cellular and molecular processes, including angiogenesis, which is vital for effective wound healing. Bletilla striata polysaccharide (BSP), a bioactive compound from Bletilla striata, exhibits anti-inflammatory and wound-healing properties. However, its impact on angiogenesis modulation, particularly through the synaptopodin-2-like (SCEL) gene, remains poorly understood. The effects of BSP on HMEC-1 cells exposed to lipopolysaccharide (LPS) were assessed using cell viability, migration, apoptosis, and angiogenesis assays. SCEL's role was explored through lentiviral transfection to manipulate SCEL expression. Animal models were employed to evaluate BSP's therapeutic potential in burn wound healing, with histological analysis, immunohistochemistry (IHC), and molecular assays to assess tissue repair and angiogenesis. BSP significantly alleviated LPS-induced damage in HMEC-1 cells by promoting cell survival, reducing apoptosis, and enhancing migration and angiogenesis. BSP treatment downregulated SCEL expression, reversing LPS-induced cellular damage. In SCEL-overexpressing cells and mice, BSP's beneficial effects on wound healing were attenuated, indicating SCEL's regulatory role in angiogenesis. In vivo, BSP accelerated burn wound closure, improved tissue organization, and enhanced angiogenesis, as evidenced by increased CD31 expression. SCEL overexpression impaired these effects, highlighting the essential role of SCEL downregulation in BSP-mediated healing. BSP promotes burn wound healing by modulating angiogenesis via SCEL downregulation, facilitating cell survival, migration, and vascularization. These findings position BSP as a promising therapeutic agent for burn wound treatment, with further investigation into SCEL's molecular mechanisms offering potential for novel wound care strategies.

Mechanism and therapeutic potential of hippo signaling pathway in type 2 diabetes and its complications.

Loss of pancreatic islet cell mass and function is one of the most important factors in the development of type 2 diabetes mellitus, and hyperglycemia-induced lesions in other organs are also associated with apoptosis or hyperproliferation of the corresponding tissue cells. The Hippo signaling pathway is a key signal in the regulation of cell growth, proliferation and apoptosis, which has been shown to play an important role in the regulation of diabetes mellitus and its complications. Excessive activation of the Hippo signaling pathway under high glucose conditions triggered apoptosis and decreased insulin secretion in pancreatic islet cells, while dysregulation of the Hippo signaling pathway in the cells of other organ tissues led to proliferation or apoptosis and promoted tissue fibrosis, which aggravated the progression of diabetes mellitus and its complications. This article reviews the mechanisms of Hippo signaling, its individual and reciprocal regulation in diabetic pancreatic pathology, and its emerging role in the pathophysiology of diabetic complications. Potential therapeutics for diabetes mellitus that have been shown to target the Hippo signaling pathway are also summarized to provide information for the clinical management of type 2 diabetes mellitus.

Xenographic lenticule implantation followed by riboflavin and UV treatment: A promising alternative for corneal ectasias management.

The cornea is the primary refracting surface of the eye, requiring precise curvature to ensure optimal vision. Any distortion in its shape may result in significant visual impairment. Corneal ectasias, such as keratoconus (KC), is characterized by gradual thinning and protrusion of the thinned area, due to biomechanical weakening of the tissue, leading to astigmatism and vision loss. KC affects approximately 1 in 2000 individuals globally. While corneal transplantation is the main treatment, limited donor availability and potential immunogenic reactions have spurred the search for alternatives. Stromal lenticule implantation using decellularized porcine corneas offers a promising solution, with reduced immunogenicity and risk of rejection. Additionally, combining this approach with riboflavin and UV radiation treatment post-surgery enhances collagen fibril cross-linking, promoting tissue integration and organization. This study evaluated the efficacy of heterologous transplantation of decellularized porcine lenticules into the corneal stroma of rabbits, followed by riboflavin application and UV radiation. Results demonstrated increased stromal thickness and no signs of tissue rejection, indicating minimal immunogenicity of the lenticules. The cross-linking technique successfully improved tissue organization, suggesting that xenographic lenticule implantation, combined with riboflavin and UV light, is a promising alternative for treating corneal ectasias like KC. Further research is necessary to confirm the long-term efficacy and safety of this method in human subjects.

TrimNN: Characterizing cellular community motifs for studying multicellular topological organization in complex tissues.

The spatial arrangement of cells plays a pivotal role in shaping tissue functions in various biological systems and diseased microenvironments. However, it is still under-investigated of the topological coordinating rules among different cell types as tissue spatial patterns. Here, we introduce the Triangulation cellular community motif Neural Network (TrimNN), a bottom-up approach to estimate the prevalence of sizeable conservative cell organization patterns as Cellular Community (CC) motifs in spatial transcriptomics and proteomics. Different from clustering cell type composition from classical top-down analysis, TrimNN differentiates cellular niches as countable topological blocks in recurring interconnections of various types, representing multicellular neighborhoods with interpretability and generalizability. This graph-based deep learning framework adopts inductive bias in CCs and uses a semi-divide and conquer approach in the triangulated space. In spatial omics studies, various sizes of CC motifs identified by TrimNN robustly reveal relations between spatially distributed cell-type patterns and diverse phenotypical biological functions.

Development and evaluation of a microfluidic human testicular tissue chip: a novel in vitro platform for reproductive biology and pharmacology studies.

Organ-on-a-chip culture systems using human organ tissues provide invaluable preclinical insights into systemic functions in vitro. This study aimed to develop a novel human testicular tissue chip within a microfluidic device employing computer-aided design software and photolithography technology. Polydimethylsiloxane was used as the primary material to ensure marked gas permeability and no biotoxicity, enabling effective mimicry of the in vivo testicular microenvironment. This biochip preserved the structural integrity and cellular composition of human testicular tissue, as well as part of its functionality, over an extended period in vitro. Moreover, compared to traditional static culture methods, it more effectively maintained tissue viability and endocrine function. The chip maintained cellular components, histological morphology, and an ultrastructure similar to those in vivo. Notably, the addition of gonadotropins to the human testis tissue on the chip resulted in consistent and steady in vitro production of testosterone and inhibin B. Additionally, the chip displayed sensitivity to the reproductive toxicity of the chemotherapeutic drug busulfan. The results demonstrate the successful establishment of a novel human testicular tissue chip culture system, providing a novel in vitro approach enabling the exploration of human reproductive biology, reproductive pharmacology, toxicology, individual diagnosis, and treatment strategies.

Susceptibility to pseudoexfoliation linked to intronic variant rs4926246 in CACNA1A: Evidence from an Indian population study.

Pseudoexfoliation (PEX) is an age-related, complex systemic disorder of protein aggregopathy. It is characterized by the extracellular fibril depositions, termed PEX fibrils, initially observed in various organ tissues during pseudoexfoliation syndrome (PEXS) and with significant prominence in the eye during advanced pseudoexfoliation glaucoma (PEXG). The study explores the association between CACNA1A (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) variants and PEX in an Indian population. The investigation involved genotyping one intronic single nucleotide polymorphism (SNP), rs4926244, and three tag SNPs using the Sanger and TaqMan genotyping approaches in a cohort of 300 controls and 300 PEX patients (including 200 PEXS and 100 PEXG cases). Findings from the present study revealed a significant association at both allelic and genotypic levels for rs4926246, whereas rs4926244 showed association only at the genotypic level with PEX. Functional assays demonstrated increased mRNA expression linked to the risk genotype of both variants and luciferase reporter assays indicated an allele-specific regulatory effect of rs4926246.While in silico analysis predicted potential transcription factor binding sites for c-Myc and Hypoxia-inducing factor-1 (HIF-1) at the rs4926246 locus, electrophoretic mobility shift assay (EMSA) validated that only the "T" variant showed the reduced binding affinity with c-Myc compared to the protective variant "C". Our study identifies rs4926246, an intronic variant strongly associated with both PEXS and PEXG, potentially influencing gene expression and protein binding, warranting further investigation into its role in PEX pathogenesis.

A Hydrogel-Based Multiplex Coculture Platform for Retinal Component Cells.

There is growing interest in generating in vitro models of tissues and tissue-related diseases to mimic normal tissue organization and pathogenesis for different purposes. The retina is a highly complex multicellular tissue where the organization of the cellular components relative to each other is critical for retinal function. Many retinopathies arise due to the disruption of this order. In this study, we aimed to generate a coculture model of retina-derived cells, namely RPE and Müller cells, in multiplexed 3D hydrogels. Using methacrylated gelatin (GelMA)-based 3D hydrogels, we compared the behavior of RPE and Müller cells when they were cultured together. These patterned multiplex hydrogels containing cells were cultured for several days to reflect how cells would reorganize themselves in the presence of another cellular component derived from the same tissue. Here, we present a multicellular multiplex platform for the creation of cellular networks with cells of retinal tissue that can be easily adapted to create more complex tissue-like alternatives for large-scale tissue modeling and screening purposes. We also present an alternative method of coculture by generating spheroids from one of the components while keeping the other component free and motile in the hydrogel. The latter model predicts enhanced possibilities of cellular interactions by retarding the movement of one of the component cells.

Associations of Maternal Prenatal Zinc Consumption with Infant Brain Tissue Organization and Neurodevelopmental Outcomes.

While studies in rat pups suggest that early zinc exposure is critical for optimal brain structure and function, associations of prenatal zinc intake with measures of brain development in infants are unknown. This study aimed to assess the associations of maternal zinc intake during pregnancy with MRI measures of brain tissue microstructure and neurodevelopmental outcomes, as well as to determine whether MRI measures of the brain mediated the relationship between maternal zinc intake and neurodevelopmental indices. Forty-one adolescent mothers were recruited for a longitudinal study during pregnancy. Maternal zinc intake was assessed during the third trimester of pregnancy using a 24 h dietary recall. Infant MRI scans were acquired at 3 weeks postpartum using a 3.0 Tesla scanner to measure fractional anisotropy (FA) and mean diffusivity (MD). Cognitive, language, and motor skills were assessed at 4, 14, and 24 months postpartum using the Bayley Scales of Infant Development. Greater prenatal zinc intake was associated with reduced FA in cortical gray matter, particularly in the frontal lobe [medial superior frontal gyrus; β (95% CI) = -1.0 (-1.5, -0.5)], in developing white matter, and in subcortical gray matter nuclei. Greater prenatal zinc intake was associated with reduced MD in cortical gray matter and developing white matter [superior longitudinal fasciculus; -4.4 (-7.1, -1.7)]. Greater maternal zinc intake also was associated with higher cognitive development scores at 14 [0.1 (0.0, 0.1)] and 24 [0.1 (0.0, 0.2)] months of age; MRI indices of FA and MD did not mediate this relationship. Maternal prenatal zinc intake was associated with more favorable measures of brain tissue microstructural maturation and cognitive development during infancy.

Leveraging Optical Anisotropy of the Morpho Butterfly Wing for Quantitative, Stain-Free, and Contact-Free Assessment of Biological Tissue Microstructures.

Changes in the density and organization of fibrous biological tissues often accompany the progression of serious diseases ranging from fibrosis to neurodegenerative diseases, heart disease and cancer. However, challenges in cost, complexity, or precision faced by existing imaging methodologies and materials pose barriers to elucidating the role of tissue microstructure in disease. Here, we leverage the intrinsic optical anisotropy of the Morpho butterfly wing and introduce Morpho-Enhanced Polarized Light Microscopy (MorE-PoL), a stain- and contact-free imaging platform that enhances and quantifies the birefringent material properties of fibrous biological tissues. We develop a mathematical model, based on Jones calculus, which describes fibrous tissue density and organization. As a representative example, we analyzed collagen-dense and collagen-sparse human breast cancer tissue sections and leverage our technique to assess the microstructural properties of distinct regions of interest. We compare our results with conventional Hematoxylin and Eosin (H&E) staining procedures and second harmonic generation (SHG) microscopy for fibrillar collagen detection. Our findings demonstrate that our MorE-PoL technique provides a robust, quantitative, and accessible route toward analyzing biological tissue microstructures, with great potential for application to a broad range of biological materials.