Search

Including sensor information in medical interventions aims to support surgeons to decide on subsequent action steps by characterizing tissue intraoperatively. With bladder cancer, an important issue is tumor recurrence because of failure to remove the entire tumor. Impedance measurements can help to classify bladder tissue and give the surgeons an indication on how much tissue to remove. Over the years of research, it became obvious that electrical impedance spectroscopy is a very promising tool for tissue differentiation, but also a very sensitive one. While differentiation in preliminary studies shows great potential, challenges arise when transferring this concept to real, intraoperative conditions, mainly due to the influence of preoperative radiotherapy, possibly different tumor types, and mechanical tissue deformations due to peristalsis or unsteady contact force of the sensor. This work proposes a patient-based classification approach that evaluates the distance of an unknown measurement to a healthy reference of the same patient, essentially a relative classification of the difference in impedance that is robust against inter-individual differences and systematic errors. A diversified dataset covering multiple disturbance scenarios is recorded. Two alternatives to define features from the impedance data are investigated, namely using measurement points and model-based parameters. Based on the distance of the feature vector of a unknown measurement to a healthy reference, a Gaussian process classifier is trained. The approach achieves a high classification accuracy of up to 100% on noise-free impedance data recorded under controlled conditions. Even when the differentiation is more ambiguous due to external disturbances, the presented approach still achieves a classification accuracy of 80%. These results are a starting point to tackle intraoperative bladder tissue characterization and decrease the recurrence rate. [ABSTRACT FROM AUTHOR]

-2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is a bioactive component in the Chinese herb Polygonum multiflorum, recognized for its anti-inflammatory and lipid-lowering properties. Human dental pulp stem cells (hDPSCs) have excellent capabilities in tooth regeneration, wound healing, and neural repair. The exosomes (Exo) released by hDPSCs contain bioactive molecules that influence cell proliferation, differentiation, and immune responses. Therefore, we aimed to unveil the potential of THSG-Exo and evaluate its regenerative capabilities through the in vitro experiment and rat bone defect model. The effects of hDPSC-derived exosomes, with or without THSG treatment, on repair and bone regeneration were evaluated through in vitro and in vivo studies. Finally, we conducted a proteomic analysis to meticulously compare the compositional contents of the two types of exosomes. In vitro data showed that 10 and 100 μM THSG-Exo enhanced cell proliferation and osteogenic differentiation, reducing wound size to 40 % of its original size. In our maxillary bone defect rat model, THSG-Exo significantly increased bone volume, trabecular thickness, and bone density in the bone defect area. In addition, proteomic analysis of THSG-Exo revealed diverse proteins linked to bone differentiation and tissue repair, including bone morphogenetic protein-1 (BMP-1) and tumor necrosis factor (TNF)-α-stimulated gene 6 (TNFAIP6). Our searches in functional databases revealed that THSG-Exo is involved in numerous biological pathways. THSG-Exo enhanced cell proliferation, wound healing, and osteogenesis in vitro , while also expediting tissue repair and bone regeneration in vivo. The protein diversity of THSG-Exo contributes significant value in both basic and regenerative medicine. [ABSTRACT FROM AUTHOR]

Males and females share most of the genome, but many animals show different phenotypes between the sexes, known as sexual dimorphism. Many insect species show extreme sexual dimorphism, including beetles with "weapon traits" represented by extremely developed horns and mandibles. Existing studies of sex‐specific development of beetle weapon traits suggest that sex‐specific gene expression plays an important role. On the other hand, contributions of the Y‐chromosome, which may potentially carry genes necessary for male development, to weapon trait expression have not been examined. In holometabolous insects, including beetles, the feminizing gene transformer (tra) is roughly conserved in its feminizing function. Only females express a functional isoform of Tra, which causes female differentiation. Knocking down tra in females leads to male tissue differentiation, enabling us to analyze male phenotypes in individuals lacking a Y‐chromosome (XX‐males). In this study, we investigate whether the Y‐chromosome is necessary for stag beetles to express male‐specific weapon traits by comparing tra‐knockdown‐induced XX‐males with natural XY males. We show that XX‐males could express weapons (enlarged mandibles) as in XY‐males. These results suggest that the Y‐chromosome does not have a major role in weapon trait expression in this species. Research Highlights: Developmental roles of Y‐chromosome on male‐specific mandible growth in stag beetles were analyzed. "XX‐male" was induced from females by suppressing feminizer gene. These XX‐males had developed mandibles, indicating the Y‐chromosome's limited role. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a vital role in maintaining the body's shape and regulating various physiological processes. Its function is influenced by a multitude of factors. Given the lack of uniformity in prior research regarding the size and placement of structural pillars within the chip, as well as the choice of cell‐laden hydrogel components with various densities of extracellular matrix, in different gelation times, and cell densities, a meticulous investigation is conducted to enhance the robustness of 3D in vitro musculoskeletal tissues. This study provides guidance on how to optimize the design parameters of skeletal muscle‐on‐a‐chip and hydrogel recipe by evaluating the impact of design elements and hydrogel fabrication conditions on tissue formation and musculoskeletal differentiation. This research reports the direct evidence of mechanical properties of hydrogels are critical in influencing cellular differentiation and tissue functionality through the process of mechanotransduction. The study highlights the importance of standardizing experimental conditions in 3D in vitro musculoskeletal research, and presents a validated framework as a foundation to aid in the development of functional musculoskeletal tissue for clinical and research applications, including disease modeling and regenerative therapies. [ABSTRACT FROM AUTHOR]

Breast cancer remains one of the most challenging diseases to treat due to its heterogeneity, propensity to recur, capacity to spread to distant vital organs, and, ultimately, patient death. Estrogen receptor-positive illness comprises the most common breast cancer subtype. Preclinical progress is hampered by the scarcity of medication-naïve estrogen receptor-positive tumour models that recapitulate metastatic development and treatment resistance. It is becoming increasingly clear that loss of differentiation and increased cellular stemness and plasticity are important causes of cancer evolution, heterogeneity, recurrence, metastasis, and treatment failure. Therefore, it has been suggested that reprogramming cancer cell differentiation could offer an effective method of reversing cancer through terminal differentiation and maturation. In this context, the hormone prolactin is well recognized for its pivotal involvement in the development of the mammary glands lobuloalveolar tissue and the terminal differentiation that drives the production of the milk protein gene and lactation. Additionally, numerous studies have examined the engagement of prolactin in breast cancer as a differentiation player that resulted in the ablation of tumour growth and progression. Here, we showed that a pre-treatment of the estrogen-positive breast cancer cell line with prolactin led to a considerable improvement in the sensitivity of this cancer cell to Tamoxifen endocrine therapy. We also showed a favourable prognostic value of prolactin receptors/estrogen receptors 1 (or alpha) co-expression on breast cancer patients outcomes, and this co-expression is highly correlated with the well-differentiated breast tumour type. Our results revealed a fruitful aspect of the effects of prolactin in improving the responses of breast cancer cells to conventional endocrine therapy. Moreover, these findings further validated the ability of prolactin as a persuader of a more differentiated and less aggressive breast cancer phenotype. Hence, it suggested a potential implication of prolactin as a therapeutic candidate. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear. Here, we use a genome-wide approach to modulate canonical androgen response element (ARE) motifs—the classic DNA binding elements for AR—to delineate distinct AR transcriptional programs. We find that activating these AREs promotes differentiation and growth-suppressive transcription, potentially leading to AR+ PCa cell death, while ARE repression is tolerated by PCa cells but deleterious to normal prostate cells. Gene signatures driven by ARE activity correlate with improved prognosis and luminal phenotypes in PCa patients. Canonical AREs maintain a normal, lineage-specific transcriptional program that can be reengaged in PCa cells, offering therapeutic potential and clinical relevance. Androgen response elements (AREs) regulation produce opposite effects in normal and cancer prostate cells. Here, authors engineer a modifier of ARE-containing chromatin (MACC) to define the elements responsible for a normal growth-suppressive program, which can be reengaged in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Euterpe edulis Martius (Arecaceae) faces a threat of extinction due to the excessive exploitation of its heart of palm. Compounded by its slow germination and the challenging nature of its seeds, there is an urgent need to explore alternative propagation methods. Somatic embryogenesis emerges as a promising alternative, offering the potential to generate somatic embryos from a single explant. Given the importance of maturing somatic embryos in this process, there is an active search for molecules capable of stimulating this stage of embryogenesis. This study aimed to assess the impact of polyamines, spermidine and spermine, on the differentiation of embryonic tissues and the maturation of somatic embryos in Euterpe edulis. The embryogenic callus were treated with different concentrations of spermine and spermidine (0, 50.0, 100.0, and 150.0 μM). Spermidine (150.0 μM) resulted in a greater number (8.67 per embryogenic callus) of somatic embryos and a greater presence of formation zones for these embryos. Moreover, it facilitated the progression of these to the last stage of development, with 80.42% of the embryos formed being converted to the final stage and 100% the embryos being regenerated into normal seedlings. Somatic embryos exhibited either a unicellular or multicellular origin, contingent upon the presence or absence of basal cells, respectively, and their developmental trajectory was asynchronous. Intensive cell division stimulated by spermidine resulted in the emergence of promeristems, initiating the formation of primary meristems such as the protoderm and procambium. In view of this it follows that 150.0 μM spermidine stimulated the maturation of somatic embryos in E. edulis. [ABSTRACT FROM AUTHOR]

Epigenetic modifications regulate chromatin accessibility, gene expression, cell differentiation and tissue development. As epigenetic modifications can be inherited via mitotic and meiotic cell divisions, they enable a heritable memory of cell identity and function and can alter inherited characteristics in the next generation. Tight regulation of epigenetic information is critical for normal cell function and is often disrupted in diseases including cancer, metabolic, neurological and inherited congenital conditions. The ovary performs critical functions in female reproductive health and fertility, including oocyte and sex-hormone production. Oocytes undergo extensive epigenetic programming including the establishment of maternal genomic imprints, which are critical for offspring health and development. Epigenetic modifiers also regulate ovarian somatic cells, such as granulosa and theca cells which support oocytes and produce hormones. While ovarian dysfunction contributes to serious ovarian conditions such as primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS) and ovarian cancers, the roles of epigenetic modifications in the ovary and their contribution to ovarian dysfunction are not properly understood. Here we review recent advancements in understanding Polycomb proteins, important epigenetic modifiers that have emerging roles in ovarian development and maternal epigenetic inheritance. Polycomb group proteins (PcGs) contribute to the faithful establishment of epigenetic information in oocytes, a process essential for normal offspring development in mice. Emerging evidence also indicates that PcGs regulate ovarian function and female fertility. Understanding these and similar mechanisms will provide greater insight into the epigenetic regulation of ovarian and oocyte function, and how its disruption can impact reproductive health and maternal inheritance. Epigenetic information is an additional layer of information on top of our genes that influences which genes are active in a given cell type. This information is critically important, but we do not fully understand how it is regulated in the ovary or eggs that give rise to the next generation. This review summarises recent discoveries exploring how epigenetic information is regulated in the ovary. Diagram by Ellen G. Jarred. This article belongs to the collection: Frontiers in Reproduction Science – Rising Stars at the Society for Reproductive Biology 2023. [ABSTRACT FROM AUTHOR]

Introduction: Generating new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, protocols to differentiate human induced pluripotent stem cells (hiPSCs) into lymphatic endothelial cells (LECs) are still lacking. Methods: Transcription factors, ETS2 and ETV2 are key regulators of embryonic vascular development, including lymphatic specification. While ETV2 has been shown to efficiently generate blood endothelial cells, little is known about ETS2 and its role in lymphatic differentiation. Here, we describe a method for rapid and efficient generation of LECs using transcription factors, ETS2 and ETV2. Results: This approach reproducibly differentiates four diverse hiPSCs into LECs with exceedingly high efficiency. Timely activation of ETS2 was critical, to enable its interaction with Prox1, a master lymphatic regulator. Differentiated LECs express key lymphatic markers, VEGFR3, LYVE-1, and Podoplanin, in comparable levels to mature LECs. The differentiated LECs are able to assemble into stable lymphatic vascular networks in vitro, and secrete key lymphangiocrine, reelin. Conclusion: Overall, our protocol has broad applications for basic study of lymphatic biology, as well as toward various approaches in lymphatic regeneration and personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction and Purpose: Mouse mesenchymal stem cells (MSCs) provide a resourceful tool to study physiological and pathological aspects of adipogenesis. Bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (ASCs) are widely used for these studies. Since there is a wide spectrum of methods available, the purpose is to provide a focused hands-on procedural guide for isolation and characterization of murine BM-MSCs and ASCs and to effectively differentiate them into adipocytes. Methods and Results: Optimized harvesting procedures for murine BM-MSCs and ASCs are described and graphically documented. Since macrophages reside in bone-marrow and fat tissues and regulate the biological behaviour of BM-MSCs and ASCs, we included a procedure to deplete macrophages from the MSC preparations. The identity and stemness of BM-MSCs and ASCs were confirmed by flow cytometry using established markers. Since the composition and concentrations of adipogenic differentiation cocktails differ widely, we present a standardized four-component adipogenic cocktail, consisting of insulin, dexamethasone, 3-isobutyl-1-methylxanthine, and indomethacin to efficiently differentiate freshly isolated or frozen/thawed BM-MSCs and ASCs into adipocytes. We further included visualization and quantification protocols of the differentiated adipocytes. Conclusion: This laboratory protocol was designed as a step-by-step procedure for harvesting murine BM-MSCs and ASCs and differentiating them into adipocytes. [ABSTRACT FROM AUTHOR]

DNA methylation and microRNA (miRNA) expression are epigenetic mechanisms essential for regulating tissue-specific gene expression and metabolic processes. However, high-resolution transcriptome, methylome, or miRNAome data is only available for a few model organisms and selected tissues. Up to date, only a few studies have reported on gene expression, DNA methylation, or miRNA expression in adult equine tissues at the genome-wide level. In the present study, we used RNA-Seq, miRNA-seq, and reduced representation bisulfite sequencing (RRBS) data from the heart, lung, and liver tissues of healthy cold-blooded horses to identify differentially expressed genes (DEGs), differentially expressed miRNA (DE miRNA) and differentially methylated sites (DMSs) between three types of horse tissues. Additionally, based on integrative omics analysis, we described the observed interactions of epigenetic mechanisms with tissue-specific gene expression alterations. The obtained data allowed identification from 4067 to 6143 DMSs, 9733 to 11,263 mRNAs, and 155 to 185 microRNAs, differentially expressed between various tissues. We pointed out specific genes whose expression level displayed a negative correlation with the level of CpG methylation and miRNA expression and revealed biological processes that they enrich. Furthermore, we confirmed and validated the accuracy of the Next-Generation Sequencing (NGS) results with bisulfite sequencing PCR (BSP) and quantitative PCR (qPCR). This comprehensive analysis forms a strong foundation for exploring the epigenetic mechanisms involved in tissue differentiation, especially the growth and development of the equine heart, lungs, and liver. [ABSTRACT FROM AUTHOR]

Native T1 mapping is a non‐invasive technique used for early detection of diffused myocardial abnormalities, and it provides baseline tissue characterization. Post‐contrast T1 mapping enhances tissue differentiation, enables extracellular volume (ECV) calculation, and improves myocardial viability assessment. Accurate and precise segmenting of the left ventricular (LV) myocardium on T1 maps is crucial for assessing myocardial tissue characteristics and diagnosing cardiovascular diseases (CVD). This study presents a deep learning (DL)–based pipeline for automatically segmenting LV myocardium on T1 maps and automatic computation of radial T1 and ECV values. The study employs a multicentric dataset consisting of retrospective multiparametric MRI data of 332 subjects to develop and assess the performance of the proposed method. The study compared DL architectures U‐Net and Deep Res U‐Net for LV myocardium segmentation, which achieved a dice similarity coefficient of 0.84 ± 0.43 and 0.85 ± 0.03, respectively. The dice similarity coefficients computed for radial sub‐segmentation of the LV myocardium on basal, mid‐cavity, and apical slices were 0.77 ± 0.21, 0.81 ± 0.17, and 0.61 ± 0.14, respectively. The t‐test performed between ground truth vs. predicted values of native T1, post‐contrast T1, and ECV showed no statistically significant difference (p > 0.05) for any of the radial sub‐segments. The proposed DL method leverages the use of quantitative T1 maps for automatic LV myocardium segmentation and accurately computing radial T1 and ECV values, highlighting its potential for assisting radiologists in objective cardiac assessment and, hence, in CVD diagnostics. [ABSTRACT FROM AUTHOR]

Simple Summary: Induced pluripotent stem cells have revolutionized biological research. These are adult cells that can be reprogrammed to differentiate into any cell type in the body. Although iPSCs have been widely studied in mammals, recent progress has extended their use to avian species, particularly chickens. Chicken iPSCs provide a unique model for investigating avian development, pathology, and genetics. Through the manipulation of these cells, researchers may get insights into cellular differentiation, disease progression, and possible tissue healing mechanisms. The development of efficient reprogramming methods, both viral and non-viral techniques, has significantly improved the generation of chicken iPSCs. In addition, a better understanding of the underlying molecular mechanisms, such as key signaling pathways and transcription factors, has driven the science forward. There are many uses of chicken-induced pluripotent stem cells. They may be used in the modeling of human diseases, the formulation of new drugs, and the engineering of genetically modified birds for agricultural purposes. As research proceeds, we are expecting more revolutionary discoveries and new uses of chicken iPSCs. The advent of iPSCs has greatly advanced the fields of degenerative biology, disease capabilities, and regenerative medicine. iPSCs are a new and compelling model system for studying biological processes, as well as evaluating novel therapeutic interventions. The concept of iPSCs was created in 2006 by Takahashi and Yamanaka, reprogramming mouse fibroblasts with the transcription factors Oct4, Sox2, Klf4, and c-Myc OSKM. Similar to ESCs, iPSCs can self-renew and differentiate into all types of cells. This approach has since been applied to the avian species (e.g., chickens), allowing new opportunities for scientific investigation. Thus, the chicken model organism fills the important gap between mammalian and non-mammalian vertebrates. The relatively short life cycle of the chicken model organism, alongside well-characterized genetics, makes it a perfect candidate for stem cell studies. With advancements in the technology behind avian iPSCs, it is now possible to generate pluripotent cells with high production rates. This allows new perspectives regarding germline transmission, tissue differentiation, and genetic trait improvement. This review summarizes the major advances made in the generation of chicken iPSCs using novel reprogramming techniques and the identification of species-specific transcription factors important for maintaining pluripotency. The applications of avian iPSCs in genetic engineering studies, disease resistance, and avian conservation are also discussed. This review will also indicate how the use of iPSCs in poultry biotechnology can further improve meat and egg production. Finally, the review discusses current challenges, such as incomplete understanding of the avian reprogramming environment and epigenetic modifications, and suggests future directions for refining the iPSC technology in avian mode. [ABSTRACT FROM AUTHOR]

Goats play a crucial role in providing humans with various types of valuable products including milk and meat. The underlying genetic mechanisms of important morphological aspects remain largely unknown in goats, highlighting the need for further investigation. A genome-wide association analysis (GWAS) was conducted for three morphological phenotypes in Egyptian goats. All animals were genotyped using the Illumina 65 K SNP BeadChips. Results of GWAS for wattles identified two significant (P ≤ 1.4 × 10–6, false discovery rate (FDR) ≤ 0.05) single nucleotide polymorphisms (SNPs) on chromosome 10 within a region (72–74 Mb) containing FMN1 and GREM1 genes that are important for limb development and growth. For horns, three significant SNPs were identified on chromosome 1 (119–131 Mb) harbouring candidate genes for embryonic development and tissue differentiation, such as CEP70, DZIP1L, CLDN18, SOX14, and SLC35G2. For supernumerary teats, four significant SNPs located on chromosomes 25 (8.7 Mb), 9 (47.8 Mb), 17 (45.1 Mb), and 28 (6.7 Mb) were identified, harbouring candidate genes involved in morphogenesis and reproductive traits such as EMP2, MDN1, PCDH10, and GHITM. This study identified novel candidate genes alongside previously reported ones in other goat breeds, suggesting their potential as candidate genes for the studied traits in Egyptian goats. [ABSTRACT FROM AUTHOR]

A combined biomaterial and cell‐based solution to heal critical size bone defects in the craniomaxillofacial area is a promising alternative therapeutic option to improve upon autografting, the current gold standard. A shape memory polymer (SMP) scaffold, composed of biodegradable poly(ε‐caprolactone) and coated with bioactive polydopamine, was evaluated with mesenchymal stromal cells (MSCs) derived from adipose (ADSC), bone marrow (BMSC), or umbilical cord (UCSC) tissue in their undifferentiated state or pre‐differentiated toward osteoblasts for bone healing in a rat calvarial defect model. Pre‐differentiating ADSCs and UCSCs resulted in higher new bone volume fraction (15.69% ± 1.64%) compared to empty (i.e., untreated) defects and scaffold‐only (i.e., unseeded) groups (4.41% ± 1.11%). Notably, only differentiated UCSCs exhibited a significant increase in new bone volume, surpassing both undifferentiated UCSCs and unseeded scaffolds. Further, differentiated ADSCs and UCSCs had significantly higher trabecular numbers than their undifferentiated counterparts, unseeded scaffolds, and untreated defects. Although the mineral density regenerated within the unseeded scaffold surpassed that achieved with cell seeding, the connectivity of this bone was diminished, as the regenerated tissue confined itself to the spherical morphology of the scaffold pores. The SMP scaffold alone, with undifferentiated BMSCs, with undifferentiated and differentiated ADSCs, and differentiated UCSCs (29.72 ± 1.49 N) demonstrated significant osseointegration compared to empty defects (14.34 ± 2.21 N) after 12 weeks of healing when assessed by mechanical push‐out testing. Based on these results and tissue availability to obtain the cells, pre‐differentiated ADSCs and UCSCs emerge as particularly promising candidates when paired with the SMP scaffold for repairing critical size bone defects in the craniofacial skeleton. [ABSTRACT FROM AUTHOR]

In head and neck surgery, continuous intraoperative tissue differentiation is of great importance to avoid injury to sensitive structures such as nerves and vessels. Hyperspectral imaging (HSI) with neural network analysis could support the surgeon in tissue differentiation. A 3D Convolutional Neural Network with hyperspectral data in the range of 400 − 1000 nm is used in this work. The acquisition system consisted of two multispectral snapshot cameras creating a stereo-HSI-system. For the analysis, 27 images with annotations of glandular tissue, nerve, muscle, skin and vein in 18 patients undergoing parotidectomy are included. Three patients are removed for evaluation following the leave-one-subjectout principle. The remaining images are used for training, with the data randomly divided into a training group and a validation group. In the validation, an overall accuracy of 98.7% is achieved, indicating robust training. In the evaluation on the excluded patients, an overall accuracy of 83.4% has been achieved showing good detection and identification abilities. The results clearly show that it is possible to achieve robust intraoperative tissue differentiation using hyperspectral imaging. Especially the high sensitivity in parotid or nerve tissue is of clinical importance. It is interesting to note that vein was often confused with muscle. This requires further analysis and shows that a very good and comprehensive data basis is essential. This is a major challenge, especially in surgery. [ABSTRACT FROM AUTHOR]

Tactile information acquired through palpation plays a crucial role in relation to surface characterisation and tissue differentiation - an essential clinical requirement during surgery. In the case of Minimally Invasive Surgery, access is restricted, and tactile feedback available to surgeons is therefore reduced. This paper presents a novel stiffness controllable, dynamic force range sensor that can provide remote haptic feedback. The sensor has an abraded optical fibre integrated into a silicone dome. Forces applied to the dome change the curvature of the optical fibres, resulting in light attenuation. By changing the pressure within the dome and thereby adjusting the sensor's stiffness, we are able to modify the force measurement range. Results from our experimental study demonstrate that increasing the pressure inside the dome increases the force range whilst decreasing force sensitivity. We show that the maximum force measured by our sensor prototype at 20 mm/min was 5.02 N, 6.70 N and 8.83 N for the applied pressures of 0 psi (0 kPa), 0.5 psi (3.45 kPa) and 1 psi (6.9 kPa), respectively. The sensor has also been tested to estimate the stiffness of 13 phantoms of different elastic moduli. Results show the elastic modulus sensing range of the proposed sensor to be from 8.58 to 165.32 kPa. [ABSTRACT FROM AUTHOR]

The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period. We demonstrate a progression from pluripotency through to tissue specification and differentiation which encompasses both surface ectodermal and neuroectodermal ocular lineages and the generation of iPSC-derived components of the developing cornea, conjunctiva, lens, and retina. Our findings not only advance the understanding of ocular development in a stem cell-based system of human origin, but also establish a robust methodological paradigm for exploring cellular and molecular dynamics during SEAM formation at single-cell resolution and highlight the potential of hiPSC-derived systems as powerful platforms for modelling human eye development and disease. Single-cell transcriptomic analyses delineate the differentiation of human iPSCs into ectodermal ocular lineages, highlighting defined developmental trajectories and the sequential formation and maturation of distinct ocular cell types in vitro. [ABSTRACT FROM AUTHOR]

Wound healing of partially incised Arabidopsis inflorescence stems constitutes cell proliferation that initiates mainly in pith tissues about 3 d after incision and the healing process that completes in about 7 d. Although the initiation mechanisms of cell proliferation have been well documented, the suppression mechanisms remain elusive. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases well known as proteolytic enzymes in animal system functioning in extracellular matrix remodeling during physiological and pathological processes, including tissue differentiation, growth, defense, wound healing and control of cancer growth. In this study, we report that At2-MMP might contribute to the suppression mechanism for cell proliferation during the tissue-repair process of incised inflorescence stems. At2-MMP transcript was gradually upregulated from day 0 to 5 after incision and slightly decreased on day 7. Morphological analysis of incised stem of defected mutant at2-mmp revealed significantly enhanced cell proliferation around the incision site. Consistent with this, semi-quantitative analysis of dividing cells displayed a significant increment in the number of dividing cells in at2-mmp as compared to wild type. These results showed that the upregulation of At2-MMP at a later stage of the wound-healing process is likely to be involved in the completion of the process by attenuating cell proliferation. [ABSTRACT FROM AUTHOR]

The transcription factor Runx2 plays a crucial role in regulating osteogenic differentiation and skeletal development. This factor not only controls the expression of genes involved in bone formation, but also interacts with signaling pathways such as the Notch pathway, which are essential for body development. However, studies have produced conflicting results regarding the relationship between Runx2 and the Notch pathway. Some studies suggest a synergistic interaction between these molecules, while others suggest an inhibitory one, for example, the interplay between Notch signaling, Runx2, and vitamin D3 in osteogenic differentiation and bone remodeling. The findings suggest a complex relationship between Notch signaling and osteogenic differentiation, with ongoing research needed to clarify the mechanisms involved and resolve existing contradictions regarding role of Notch in this process. Additionally, there is increasing evidence of contradictory roles for Runx2 in various tissues and organs, both under normal conditions and in pathological states. This diversity of roles makes Runx2 a potential therapeutic target, offering new directions for research. In this review, we have discussed the mechanisms of osteogenic differentiation and the important role of Runx2 in this process. We have also examined its relationship with different signaling pathways. However, there are still many uncertainties and inconsistencies in our current understanding of these interactions. Additionally, given that Runx2 is also involved in numerous other events in various tissues, we have tried to comprehensively examine its functions outside the skeletal system. [ABSTRACT FROM AUTHOR]

Placental‐derived stromal‐like cells (PLX‐PAD) have been shown to facilitate muscle tissue recovery after injury and stimulate angiogenesis. This work assesses the impact of PLX‐PAD cells on the vascularization and maturation of engineered skeletal muscle tissue. Specifically, their effects in direct co‐culture with endothelial cells, pericytes, and myoblasts seeded within microporous 3D scaffolds are characterized. Additionally, the impact of hypoxic PLX‐PAD cell‐conditioned medium (CM) on vascularization and muscle differentiation of engineered tissue is monitored. Co‐culture of PLX‐PAD with myocytes stimulated myocyte differentiation while PLX‐PAD CM promoted the formation of vascular networks. Implantation of a multi‐culture system of vascularized human skeletal muscle tissue and PLX‐PAD into a rectus abdominal defect in nude mice promoted myocyte differentiation, host vessel penetration, and tissue integration. These findings indicate the ability of placenta‐derived cells to induce the formation of vascularized engineered muscle constructs with potential therapeutic applications. [ABSTRACT FROM AUTHOR]

The study published in the journal "Allergy" explores the expression of IL-5 receptors in human sinonasal epithelial cells. The research found that while these cells express IL-5Rα, they lack the CSF2RB co-receptor necessary for IL-5 signaling. This discovery suggests tissue-specific differences in IL-5 responsiveness between upper and lower airway epithelial cells, with implications for respiratory diseases and targeted therapies. The study also highlights potential variations in the efficacy of anti-IL-5 treatments for asthma and chronic rhinosinusitis with nasal polyps. [Extracted from the article]

The physiological functions of specific areas of the nervous system, such as the spinal cord, are directional dependent, relying on the ordered arrangement of cells and extracellular matrix. Here, an automated electrospinning method is used to make fibers with different diameters by changing the concentrations of polycaprolactone/gelatine solutions. The impact of fiber diameter, orientation, and the inclusion of superparamagnetic iron oxide nanoparticles on neural stem cell (NSC) behavior and differentiation is investigated. Fibers with an average diameter of 1189 ± 274 nm greatly improve neuronal differentiation. The highest relative expression of the neuronal marker Tuj‐1 and the formation of interconnected neuronal networks with neurites aligned along the fiber axis demonstrate this. Incorporating SPIONS into the fibers do not damage the cells, and aligned fibers do much better than random fibers at cell proliferation, migration, and neurite alignment. Further, magnetoresponsive fiber‐based hydrogels are fabricated by embedding SPIONS‐loaded fibers within a collagen matrix, which enables remote alignment of the fibers via a magnetic field. Postcrosslinking maintains this alignment and induces significant neurite orientation within the hydrogels. The potential use of automated, magnetically responsive electrospun fibers as flexible supports for NSC differentiation and neural tissue engineering guidance is demonstrated. [ABSTRACT FROM AUTHOR]

Background: Stereotactic MR‐guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low‐field MR‐Linac faces substantial challenges due to dramatically lower signal‐to‐noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1‐to‐noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen‐enhanced (OE)‐MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1‐weighted contrast images with simultaneous T1 mapping. Purpose: To optimize MP2RAGE for low‐field T1 mapping; conduct experimental validation in a ground‐truth phantom; establish feasibility and reproducibility of low‐field MP2RAGE acquisition and T1 mapping in healthy volunteers. Methods: The MP2RAGE optimization was performed to maximize the contrast‐to‐noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low‐field MP2RAGE images were acquired on a 0.35T MR‐Linac (ViewRay MRIdian) using a multi‐channel head coil. Validation of T1 mapping was performed with a ground‐truth Eurospin phantom, containing inserts of known T1 values (400–850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (± SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole‐brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (± SD) T1 values for WM and GM were determined. Whole‐brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel‐by‐voxel T1 difference maps were generated to evaluate 3D spatial variation. Results: Low‐field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250 ms, inversion times (TI1/TI2) of 500/1200 ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, T1NR of 20.13 ± 5.31, and CV of 2.22% ± 0.67% across all inserts. Whole‐brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (± SD) T1 values: 435.36 ± 10.01 ms for WM and 623.29 ± 14.64 ms for GM across subjects, showing excellent concordance with literature. Whole‐brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel‐level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel‐by‐voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM. Conclusions: Low‐field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE‐MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR‐guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging‐to‐treat cancers. [ABSTRACT FROM AUTHOR]

Poplars are essential tree species with critical roles in wood production, ecological conservation, environmental protection, and climate change mitigation. Plants of different poplar populations exhibit varying responses to biotic and abiotic stresses, largely driven by phytohormones—key regulators of plant growth and stress responses. Phytohormones control fundamental processes such as cell division, growth, tissue differentiation, organ development, and resistance to environmental challenges such as temperature extremes and drought. In this study, we conducted a quantitative analysis of phytohormone levels in the leaves of two populations of poplar species from the same geographical region over a one-year period, covering the early, mid, and late growth stages. Our results revealed that salicylic acid (SA) and jasmonic acid (JA) concentrations in the stress-resistant poplar (RP) increased significantly during the late growth stage (September), particularly in response to elevated pathogen pressure and fluctuating climatic conditions. In contrast, the susceptible poplar (SP) consistently exhibited lower levels of SA and JA across all growth stages, particularly during the mid-growth stage (characterized by high temperatures and low precipitation) and the late growth stage, when pathogen stress typically intensifies. The limited increase in phytohormone levels in the SP suggests a weaker defense response compared with the RP. These findings demonstrate that climatic factors significantly influence the phytohormonal dynamics in poplars, with the RP exhibiting more robust regulation of SA and JA to mitigate both biotic and abiotic stresses. This study provides a theoretical framework for better understanding the resistance mechanisms in Populus and offers insights for improving stress tolerance in future breeding programs. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) spectroscopy is a powerful non-invasive technique for assessing the optical properties of human tissues, capturing spectral signatures that reflect their biochemical and structural characteristics. In this study, we investigated the use of NIR reflectance spectroscopy combined with chemometric analysis to distinguish between patients with Essential Tremor (ET) and healthy individuals. ET is a common movement disorder characterized by involuntary tremors, often making it difficult to clinically differentiate from other neurological conditions. We hypothesized that NIR spectroscopy could reveal unique optical fingerprints that differentiate ET patients from healthy controls, potentially providing an additional diagnostic tool for ET. We collected NIR reflectance spectra from both extracranial (biceps and triceps) and cranial (cerebral cortex and brainstem) sites in ET patients and healthy subjects. Using Partial Least Squares Discriminant Analysis (PLS-DA) and Partial Least Squares (PLS) regression models, we analyzed the optical properties of the tissues and identified significant wavelength peaks associated with spectral differences between the two groups. The chemometric analysis successfully classified subjects based on their spectral profiles, revealing distinct differences in optical properties between cranial and extracranial sites in ET patients compared to healthy controls. Our results suggest that NIR spectroscopy, combined with machine learning algorithms, offers a promising non-invasive method for the in vivo characterization and differentiation of tissues in ET patients. [ABSTRACT FROM AUTHOR]

Abstract Including sensor information in medical interventions aims to support surgeons to decide on subsequent action steps by characterizing tissue intraoperatively. With bladder cancer, an important issue is tumor recurrence because of failure to remove the entire tumor. Impedance measurements can help to classify bladder tissue and give the surgeons an indication on how much tissue to remove. Over the years of research, it became obvious that electrical impedance spectroscopy is a very promising tool for tissue differentiation, but also a very sensitive one. While differentiation in preliminary studies shows great potential, challenges arise when transferring this concept to real, intraoperative conditions, mainly due to the influence of preoperative radiotherapy, possibly different tumor types, and mechanical tissue deformations due to peristalsis or unsteady contact force of the sensor. This work proposes a patient-based classification approach that evaluates the distance of an unknown measurement to a healthy reference of the same patient, essentially a relative classification of the difference in impedance that is robust against inter-individual differences and systematic errors. A diversified dataset covering multiple disturbance scenarios is recorded. Two alternatives to define features from the impedance data are investigated, namely using measurement points and model-based parameters. Based on the distance of the feature vector of a unknown measurement to a healthy reference, a Gaussian process classifier is trained. The approach achieves a high classification accuracy of up to 100% on noise-free impedance data recorded under controlled conditions. Even when the differentiation is more ambiguous due to external disturbances, the presented approach still achieves a classification accuracy of 80%. These results are a starting point to tackle intraoperative bladder tissue characterization and decrease the recurrence rate.

The interaction between the surgical instrument and tissue is a yet little-exploited source of information. Vibroacoustic signals resulting from an interaction can be analyzed to extract relevant information related to the tissue. This work presents a summary of feasibility studies with synthetic-, animal-, and ex-vivo tissue specimen. A standard palpation probe is equipped with a vibration measurement system. A manual and robot-assisted setup is used for data acquisition. Simple features derived from the signals are used in a subsequent classification step using kNN and SVM. The obtained results show the capability to differentiate various tissues, such as subchondral bone with an accuracy of 98.44%. This demonstrates the potential of the approach to provide tissue related information based on instrument interactions.

Background: Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. Methods: Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. Results: The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation. Conclusion: This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy. Key points: • Precursors of pediatric acute lymphoblastic leukemia may be of epigenetic origin, detectable since birth and affecting patient prognosis. • These epigenetic precursors can be robust over several years and across several populations, ethnicities and surrogate and target tissues. [ABSTRACT FROM AUTHOR]

Our research explores the detrimental effects of microplastic (MP) exposure on adipose tissue aging and function, emphasizing the potential health risks associated with environmental pollutants. Utilizing both in vivo and in vitro models, we discovered that MPs accumulate in adipose tissues, leading to cellular senescence, inflammation, and hindered adipogenic differentiation. Notably, our findings demonstrate that MPs prompt an aging response in both epididymal and inguinal white adipose tissue, increase senescence-associated β-galactosidase activity, and upregulate key senescence and inflammatory markers. Furthermore, we show that MPs disrupt normal adipogenic differentiation by reducing lipid droplet formation and downregulating critical adipogenic markers. These insights highlight the urgent need for further investigation into the long-term consequences of MP pollution on biological aging and underscore the importance of developing public health strategies to mitigate these effects. [ABSTRACT FROM AUTHOR]

Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While granule cell cilia are essential during early developmental stages, they become infrequent upon maturation. Here, we provide nanoscopic resolution of cilia in situ using large-scale electron microscopy volumes and immunostaining of mouse cerebella. In many granule cells, we found intracellular cilia, concealed from the external environment. Cilia were disassembled in differentiating granule cell neurons—in a process we call cilia deconstruction—distinct from premitotic cilia resorption in proliferating progenitors. In differentiating granule cells, cilia deconstruction involved unique disassembly intermediates, and, as maturation progressed, mother centriolar docking at the plasma membrane. Unlike ciliated neurons in other brain regions, our results show the deconstruction of concealed cilia in differentiating granule cells, which might prevent mitogenic hedgehog responsiveness. Ciliary deconstruction could be paradigmatic of cilia removal during differentiation in other tissues. [ABSTRACT FROM AUTHOR]

Mitochondria are the energy source for basal cell functions as well as for tissue repair and regeneration. Excessive accumulation of reactive oxygen species (ROS) generated by bone tissue injury can cause cell oxidative stress and mitochondrial damage, negatively affecting osteogenic differentiation and tissue repair. However, efficient scavenging of mitochondrial ROS (mtROS) and restoration of mitochondrial homeostasis remain challenging. In this study, mitochondria‐targeted polyphenol/amino acid assembled nanoparticles (denoted as EC NPs) are constructed, which can achieve efficient intracellular ROS scavenging, especially for mtROS, recover the mitochondrial membrane potential, and enhance the inherent antioxidant system by increasing the antioxidase activity and GSH levels, following the re‐establishment of redox homeostasis. The EC NPs promoted AMPK‐mediated mitochondrial biogenesis, thereby providing more energy for osteogenic differentiation. Furthermore, the EC NPs not only recovered the osteogenic potential of the stem cells under oxidative stress but also demonstrated the ability to directly promote osteogenic differentiation by activating the cGMP‐PKG signaling pathway. In vivo experiments showed that the EC NPs significantly enhanced mitochondrial biogenesis and facilitated bone regeneration with a higher bone mass and bone mineral density. Thus, this multifunctional mitochondria‐targeted nanosystem represents a promising therapeutic strategy for bone regeneration based on mitochondrial homeostasis regulation. [ABSTRACT FROM AUTHOR]

Increased prevalence of skin ageing is a growing concern due to an ageing global population and has both sociological and psychological implications. The use of more clinically predictive in vitro methods for dermatological research is becoming commonplace due to initiatives and the cost of clinical testing. In this study, we utilise a well‐defined and characterised bioengineered skin construct as a tool to investigate the cellular and molecular dynamics involved in skin ageing from a dermal perspective. Through incorporation of ageing fibroblasts into the dermal compartment we demonstrate the significant impact of dermal‐epidermal crosstalk on the overlying epidermal epithelium. We characterise the paracrine nature of dermal‐epidermal communication and the impact this has during skin ageing. Soluble factors, such as inflammatory cytokines released as a consequence of senescence associated secretory phenotype (SASP) from ageing fibroblasts, are known to play a pivotal role in skin ageing. Here, we demonstrate their effect on epidermal morphology and thickness, but not keratinocyte differentiation or tissue structure. Through a novel in vitro strategy utilising bioengineered tissue constructs, this study offers a unique reductionist approach to study epidermal and dermal compartments in isolation and tandem. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are plant steroid hormones that control growth and stress responses. In the context of development, BRs play diverse roles in controlling cell differentiation and tissue patterning. The vascular system, which is essential for transporting water and nutrients throughout the plant body, initially establishes a tissue pattern during primary development and then dramatically increases the number of vascular cells during secondary development. This complex developmental process is properly regulated by a network consisting of various hormonal signaling pathways. Genetic studies have revealed that mutants that are defective in BR biosynthesis or the BR signaling cascade exhibit a multifaceted vascular development phenotype. Furthermore, BR crosstalk with other plant hormones, including peptide hormones, coordinately regulates vascular development. Recently, the involvement of BR in vascular development, especially in xylem differentiation, has also been suggested in plant species other than the model plant Arabidopsis thaliana. In this review, we briefly summarize the recent findings on the roles of BR in primary and secondary vascular development in Arabidopsis and other species. [ABSTRACT FROM AUTHOR]

Simple Summary: Skeletal muscle is an endocrine organ capable of responding to and releasing hormones and hormonally active molecules. In particular, sex hormones (e.g., testosterone) specifically regulate metabolic activity, growth, and tissue differentiation. However, the biological and clinical responses to the same type of hormone treatment differ between subjects with male and female karyotypes. Characterization of the biomolecular mechanisms underlying the sexual dimorphism in response to sex hormones is crucial for the design of new methodological approaches aimed at highlighting sex differences in the patho/physiological aspects caused by the use (and abuse) of sex hormones. To date, in vivo and ex vivo studies are very limited, mainly for ethical reasons; it is therefore of fundamental importance to use experimental approaches based on cellular models at the preclinical level. On the other hand, most in vitro studies do not take into account the chromosomal structure of the cell models used, with the result that 'sex' is often a 'confounding factor'. This highlights the need for basic research to develop preclinical models that take into account chromosomal sex differences to ensure the transferability of the data obtained in vivo and to adequately design relevant experimental studies. Therefore, given the role of skeletal muscle in biological responses to testosterone, the aim of this project is to assess the presence of sex differences in endocrine–metabolic cellular responses to increasing doses of testosterone by simulating functional modifications of skeletal muscle cells in vitro. Muscle tissue is an important target of sex steroids, and particularly, testosterone plays essential roles in muscle cell metabolism. Wide ranges of studies have reported sex differences in basal muscle steroidogenesis, and recently several genes have been identified to be regulated by androgen response elements that show innate sex differences in muscle. However, studies accounting for and demonstrating cell sexual dimorphism in vitro are still scarce and not well characterized. Here, we demonstrated the ability of 46XX and 46XY human primary skeletal muscle cells to differently activate steroidogenesis in vitro, likely related to sex-chromosome onset, and to differently induce hormone release after increasing doses of testosterone exposure. Cells were treated with testosterone at concentrations of 0.5, 2, 5, 10, 32, and 100 nmol/L for 24 h. Variations in 17β-HSD, 5α-R2, CYP-19 expression, DHT, estradiol, and androstenedione release, as well as IL6 and IL8 release, were analyzed, respectively, by RT-PCR, ELISA, and luminex-assay. Following testosterone treatments, and potentially at any concentration level, an increase in the expression of 17β-HSD, 5α-R2, and CYP-19 was observed in 46XY cells, accompanied by elevated levels of DHT, androstenedione, and IL6/IL8 release. Following the same treatment, 46XX cells exhibited an increase in 5α-R2 and CYP-19 expression, a conversion of androgens to estrogens, and a reduction in IL6 and IL8 release. In conclusion, this study demonstrated that sex-chromosome differences may influence in vitro muscle cell steroidogenesis and hormone homeostasis, which are pivotal for skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of long non-coding RNA LINC00261 in regulating E26 transcription factor 1 (EST1) by interfering with the expression of miR-324-3p in promoting the development of gastric cancer (GC). Methods: Cancer tissues and corresponding adjacent normal tissues of GC patients (n=80) who underwent surgical treatment in 363 Hospital from June 2018 to October 2020 were collected as research samples, and the expression levels of LINC00261 and miR-324-3p were detected by qRT-PCR. The correlation between LINC00261 and clinicopathological parameters were analyzed. siRNA (si-LINC00261), miRNA mimic (miR-324-3p), miRNA inhibitor (miR-324-3p in) and their corresponding controls were transfected into MGC-803 and SGC- 7901 cells. Clonogenesis assay was used to evaluate cell proliferation. The Transwell assay assessed cell migration and invasion. The protein expression levels of E-cadherin, N-cadherin and ETS1 were detected by Western blot. Tumor xenotransplantation assay was used to detect the tumorigenesis of LINC00261 in vivo. Luciferase report and RNA precipitation were used to analyze the interaction between LINC00261, miR-324-3p and EST1. Results: Compared with adjacent tissues, the expression of LINC00261 in GC tissues was significantly up-regulated with statistical significance (P<0.05). The expression of LINC00261 was correlated with TNM stage, tissue differentiation degree, lymph node metastasis and microvascular invasion (P<0.05). The database prediction, firefly luciferase assay and RNA immunoprecipitation results showed that LINC00261 had a targeted relationship with miR-324-3p. The level of miRdoi: 324-3p in GC tissues was significantly lower than that in paracellular normal tissues (P<0.05). There was a negative correlation between miR-324-3p level and LINC00261 expression (P<0.05). Compared with in NC+si-NC group, the cell proliferation, migration and invasion ability and the expression of N-cadherin in in NC+si-LINC00261 group were significantly inhibited (P<0.05), while the expression of E-cadherin was significantly increased (P<0.05). Compared with in NC+si-LINC00261 group, cell proliferation, migration and invasion ability and expression of N-cadherin in si-LINC00261+miR-324-3p in group were significantly increased (P<0.05), while the expression of E-cadherin was significantly decreased (P<0.05). Targetscan prediction and firefly luciferase assay showed that ETS1 was the downstream binding site of miR-324-3p. After transfection with miR-324-3p, ETS1 protein level was significantly down-regulated (P<0.05), but after transfection with miR-324-3p in, ETS1 protein level was significantly up-regulated (P<0.05). The expression of ETS1 in GC tissue was significantly higher than that in adjacent normal tissue (P<0.05). The miR-324-3p level was negatively correlated with ETS1 (P<0.05). The tumor weight of MGC-803 cells transfected with si-LINC00261 was lower than that of MGC-803 cells transfected with si-NC (P<0.05), and the protein level of ETS1 in si-LINC00261-derived tumors was lower than that of si-NC tumors (P<0.05). Conclusion: LINC00261 is highly expressed in GC tissue, which may affect EST1 expression and promote GC progress by regulating miR-324-3p. [ABSTRACT FROM AUTHOR]

This article explores the impact of different treatments on patients with plaque psoriasis. It specifically focuses on the use of epigenetic 'clock' algorithms to determine the biological age of patients. The study found that individuals who responded poorly to treatment had an accelerated biological age compared to those who responded well and healthy individuals. Furthermore, the study discovered that phototherapy treatment had a positive effect on biological age and leukocyte composition in psoriasis patients, bringing them closer to the biological age of healthy individuals. These findings suggest that DNA methylation-based algorithms can be used to assess the effectiveness of psoriasis treatments and gain a better understanding of the molecular changes associated with the disease. [Extracted from the article]

Various materials have been used to promote human dental pulp stem cells (hDPSCs) differentiation to produce dentin bridge formation with less-than-optimal results. Polydatin (PD), a naturally present material with osteogenic properties can be a promising material in the pulp regeneration/repair process. The aim of this study was to evaluate the effect of (PD) on the viability and differentiation of human dental pulp stem cells. PD effect on hDPSCs in terms of cellular viability, alkaline phosphatase (ALP) production, and messenger RNAs (mRNA) of odontogenic markers production using quantitative reverse transcription polymerase chain reaction (RT-qPCR) were evaluated. In addition, mineral deposits were detected with Alizarin red stain. The viable hDPSCs in the presence of 0.01 μM and 0.1 μM PD were significantly higher than the control on days 3 and 7, respectively. In addition, ALP activity of hDPSCs was significantly increased with 0.01, 0.1, and 1 μM of PD. In addition, increased expression mRNAs of ALP, osteocalcin (OC), osteonectin (ON), osteopontin (OP), Runt-related transcription factor-2 (RUNX-2), dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) was observed after PD treatment, however, the difference was not statistically significant. Furthermore, increased size of mineral deposits was observed with PD. PD promoted the expression of markers associated with odontogenic differentiation and mineralized tissue deposition in hDPSCs. [ABSTRACT FROM AUTHOR]

Myocardial infarction is one of the main causes of death worldwide. After myocardial infarction, the damaged area is typically occupied with non‐contractile scar tissue owing to the limited ability of cardiac cells to proliferate. Cardiac patches can potentially restore heart function by providing sufficient electrochemical properties to the damaged area and supporting the differentiation into and proliferation of cardiac cells. In this study, we developed for the first time a poly(mannitol sebacate) (PMS) based scaffold combined with 1% (w/w)multi‐walled carbon nanotubes (MWCNTs) to produce a biocompatible cardiac patch by the solvent casting method. We characterized the resultant PMS‐MWCNT scaffold in terms of chemical, physical, mechanical and electrical properties. The PMS/MWCNT patch revealed appropriate hydrophilicity, elasticity close to that of the target tissue, and electrical conductivity suited for a cardiac patch. The cytocompatibility of the composite was confirmed by the successful attachment and proliferation of human umbilical cord mesenchymal stem cells (HUC‐MSCs). The PMS/MWCNTs further contributed to the differentiation of HUC‐MSCs by significant overexpression of cardiac‐specific proteins, i.e. troponin T and connexin 43, in the presence of 5‐azacytidine. The findings of this study could be of assistance in the use and development of PMS‐based composites as cardiac patches for myocardial tissue engineering applications. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Bone ingrowth into a porous implant is necessary for its long-term fixation. Although attempts have been made to quantify the peri-implant bone growth using finite element (FE) analysis integrated with mechanoregulatory algorithms, bone ingrowth into a porous cellular hip stem has scarcely been investigated. Using a three-dimensional (3D) FE model and mechanobiology-based numerical framework, the objective of this study was to predict the spatial distribution of evolutionary bone ingrowth into an uncemented novel porous hip stem proposed earlier by the authors. A CT-based FE macromodel of the implant-bone structure was developed. The bone material properties were assigned based on CT grey value. Peak musculoskeletal loading conditions, corresponding to level walking and stair climbing, were applied. The geometry of the implant-bone macromodel was divided into multiple submodels. A suitable mapping framework was used to transfer maximum nodal displacements from the FE macromodel to the cut boundaries of the FE submodels. CT grey value-based bone materials properties were assigned to the submodels. Thereafter, the submodels were solved and simulations of bone ingrowth were carried out using mechanoregulatory principle. A gradual increase in the average Young's modulus, from 1200 to 1500 MPa, of the bone tissue layer was observed considering all the submodels. The distal submodel exhibited 82% of bone ingrowth, whereas the proximal submodel experienced 65% bone ingrowth. Equilibrium in the bone ingrowth process was achieved in 7 weeks postoperatively, with a notable amount of bone ingrowth that should lead to biological fixation of the novel hip stem. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate a multiparametric exchange proton approach using CEST and Z‐spectrum analysis protons (ZAP) in human abdominal organs, focusing on tissue differentiation for a potential early biomarker of abnormality. Prior to human studies, CEST and ZAP effects were studied in phantoms containing exchange protons. Methods: Phantoms composed of iopamidol and iohexol solutions with varying pH levels, along with 12 human subjects, were scanned on a clinical 3T MR scanner. Subsequent ZAP analyses employed a two‐Lorentzian pool model to provide free and restricted apparent T2f,rex$$ {\mathrm{T}}_{2\ \mathrm{f},\mathrm{r}}^{\mathrm{ex}} $$, and their fractions for data acquired across a wide range of offset frequencies (±100 kHz or ± 800 ppm), while a narrower range (±7 ppm or ± 900 Hz) was used for CEST analysis to estimate magnetization transfer ratio asymmetry (MTRAsym) for exchange protons like hydroxyl (—OH), amine (—NH2), and amide (—NH), resonating ˜1, 2, and 3.5 ppm, respectively. Differences in ZAP metrics across various organs were statistically analyzed using one‐way analysis of variance (ANOVA). Results: The phantom study differentiated contrast agents based on resonance peaks detected from CEST analysis, while ZAP metrics showed sensitivity to pH variations. In human, ZAP metrics revealed significant differences in abdominal organs, with a subgroup study indicating changes in ZAP metrics due to the presence of gallstones. Conclusion: CEST and ZAP techniques demonstrated promise in specific CEST protons and wide range ZAP protons and identifying tissue‐specific characteristics. The preliminary findings underscore the necessity for more extensive study involving a broader subject pool to potentially establish biomarkers for diseased states. [ABSTRACT FROM AUTHOR]

Human periodontal ligament stem cells (hPDLSCs) differentiate into periodontal ligament (PDL) fibroblasts, osteoblasts, and cementoblasts. To identify inducers of PDL fibroblastic differentiation, monoclonal antibody series were developed a series of against membrane/extracellular matrix (ECM) molecules through decoy immunization. The anti-PDL13 antibody targets ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), renowned for regulating skeletal and soft tissue mineralization. ENPP1 accumulates in the periodontal ligament region of tooth roots, and specifically localizes to the cell boundaries and elongated processes of the fibroblastic cells. As ENPP1 expression increases during fibroblastic differentiation, mineralization induced by tissue-nonspecific alkaline phosphatase (TNAP), a pyrophosphate-degrading enzyme, is completely inhibited. This is consistent with ENPP1 and TNAP acting in opposition, and TGF-ß1-induced ENPP1 expression creates an essential environment for PDL fibroblast differentiation. Representative fibroblastic differentiation markers decrease with endogenous ENPP1 inhibition by siRNA and antibody blocking. ENPP2 generates lipid signaling molecules. In contrast to ENPP1, ENPP2 disappears in TGF-ß1-induced PDL fibroblasts. Ectopic expression of ENPP2 hinders TGF-ß1-induced PDL fibroblastic differentiation. Suppression of ENPP1 and ENPP2 leads to severe defects in undifferentiated and differentiated cells, demonstrating that these two factors play opposing roles in soft and hard tissue differentiation but can complement each other for cell survival. In conclusion, increased ENPP1 is crucial for TGF-ß1-induced PDL differentiation, while ENPP2 and TNAP can inhibit ENPP1. ENPP1 and ENPP2 exhibit complementary functions in the cell survival. [ABSTRACT FROM AUTHOR]

In recent years, with the advent of a super-aged society, lifelong dental care has gained increasing emphasis, and implant therapy for patients with an edentulous jaw has become a significant option. However, for implant therapy to be suitable for elderly patients with reduced regenerative and immunological capabilities, higher osteoconductive and antimicrobial properties are required on the implant surfaces. Silicon nitride, a non-oxide ceramic known for its excellent mechanical properties and biocompatibility, has demonstrated high potential for inducing hard tissue differentiation and exhibiting antibacterial properties. In this study, silicon nitride was deposited on pure titanium metal surfaces and evaluated for its biocompatibility and antibacterial properties. The findings indicate that silicon nitride improves the hydrophilicity of the material surface, enhancing the initial adhesion of rat bone marrow cells and promoting hard tissue differentiation. Additionally, the antibacterial properties were assessed using Staphylococcus aureus, revealing that the silicon nitride-coated surfaces exhibited significant antibacterial activity. Importantly, no cytotoxicity was observed, suggesting that silicon nitride-coated titanium could serve as a novel implant material. [ABSTRACT FROM AUTHOR]

A 69-year-old White man was referred to a dermatologist with an asymptomatic lesion on the nape of his neck. The lesion was a cherry-red plaque with no surface change. The patient had no history of trauma, skin cancer, or immunocompromisation. A biopsy revealed sun-damaged skin with thin-walled vessels and a mild lymphocytic infiltrate, leading to a diagnosis of acquired elastotic haemangioma (AEH). AEH is a rare condition that typically presents as a slow-growing plaque or patch on sun-exposed skin in older individuals. Treatment is not necessary, but excision may be performed for diagnostic purposes. [Extracted from the article]

Osteoarthritis is a prevalent joint disease affecting both humans and animals. It is characterized by articular cartilage degeneration and joint surface eburnation. Currently, no effective pharmacological treatment is available to restore the original function and structure of defective cartilage.This study explores the potential of stem cell-based therapy in treating joint diseases involving cartilage degeneration, offering a promising avenue for future research and treatment. The primary aim was to compare the characteristics and, more importantly, the chondrogenic differentiation potential of human and rat adipose-derived mesenchymal stem cells (AD-MSCs).Rat adipose tissue was collected from Sprague Dawley rats, while human adipose tissue was obtained in the form of lipoaspirate. The mesenchymal stem cells (MSCs) were then harvested using collagenase enzyme and subcultured. We meticulously evaluated and compared the cell morphology, percentage of cell viability, population doubling time, metabolic proliferation, and chondrogenic differentiation potential of MSCs harvested from both sources. Chondrogenic differentiation was induced at passage 3 using the 3D pellet culture method and assessed through histological and molecular analysis.The findings revealed that human and rat AD-MSCs were phenotypically identical, and an insignificant difference was found in cell morphology, percentage of cell viability, metabolic proliferation, and population doubling time. However, the chondrogenic differentiation potential of human AD-MSCs was evaluated as significantly higher than that of rat AD-MSCs.The current study suggests that research regarding chondrogenic differentiation of rat AD-MSCs can be effectively translated to humans. This discovery is a significant contribution to the field of regenerative medicine and has the potential to advance our understanding of stem cell-based therapy for joint diseases. [ABSTRACT FROM AUTHOR]

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH. Methods: Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining. Results: The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression. Conclusion: CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1b involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Epithelial barriers, such as the lungs and skin, face the challenge of providing the tissues’ physiological function and maintaining tolerance to the commensal microbiome and innocuous environmental factors while defending the host against infectious microbes. Asthma and allergic diseases can result from maladaptive immune responses, resulting in exaggerated and persistent type 2 immunity and tissue inflammation. Summary: Among the diverse populations of tissue immune cells, CD4+ regulatory T cells (Treg cells) are central to controlling immune responses and inflammation and restoring tissue homeostasis. Humans and mice that are deficient in Treg cells experience extensive inflammation in their mucosal organs and skin. During past decades, major progress has been made toward understanding the immunobiology of Treg cells and the molecular and cellular mechanisms that control their differentiation and function. It is now clear that Treg cells are not a single cell type and that they demonstrate diversity and plasticity depending on their differentiation stages and tissue environment. They could also take on a proinflammatory phenotype in certain conditions. Key Messages: Treg cells perform distinct functions, including the induction of immune tolerance, suppression of inflammation, and promotion of tissue repair. Subsets of Treg cells in mucosal tissues are regulated by their differentiation stage and tissue inflammatory milieu. Treg cell dysfunction likely plays roles in persistent immune responses and tissue inflammation in asthma and allergic diseases. [ABSTRACT FROM AUTHOR]

Sugar beet (Beta vulgaris L.) is one of the most important sugar crops, accounting for nearly 30% of the world's annual sugar production. And it is mainly distributed in the northwestern, northern, and northeastern regions of China. However, Cercospora leaf spot (CLS) is the most serious and destructive foliar disease during the cultivation of sugar beet. In plants, the bZIP gene family is one of important family of transcription factors that regulate many biological processes, including cell and tissue differentiation, pathogen defense, light response, and abiotic stress signaling. Although the bZIP gene family has been mentioned in previous studies as playing a crucial role in plant defense against diseases, there has been no comprehensive study or functional analysis of the bZIP gene family in sugar beet with respect to biotic stresses. In this study, we performed a genomewide analysis of bZIP family genes (BvbZIPs) in sugar beet to investigate their phylogenetic relationships, gene structure and chromosomal localization. At the same time, we observed the stomatal and cell ultrastructure of sugar beet leaf surface during the period of infestation by Cercospora beticola Sacc (C. beticola). And identified the genes with significant differential expression in the bZIP gene family of sugar beet by qRT-PCR. Finally we determined the concentrations of SA and JA and verified the associated genes by qRT-PCR. The results showed that 48 genes were identified and gene expression analysis indicated that 6 BvbZIPs were significantly differential expressed in C. beticola infection. It is speculated that these BvbZIPs are candidate genes for regulating the response of sugar beet to CLS infection. Meanwhile, the observation stomata of sugar beet leaves infected with C. beticola revealed that there were also differences in the surface stomata of the leaves at different periods of infection. In addition, we further confirmed that the protein encoded by the SA signaling pathway-related gene BVRB_ 9g222570 in high-resistant varieties was PR1, which is closely related to systemic acquired resistance. One of the protein interaction modes of JA signal transduction pathway is the response of MYC2 transcription factor caused by JAZ protein degradation, and there is a molecular interaction between JA signal transduction pathway and auxin. Despite previous reports on abiotic stresses in sugar beet, this study provides very useful information for further research on the role of the sugar beet bZIP gene family in sugar beet through experiments. The above research findings can promote the development of sugar beet disease resistance breeding. [ABSTRACT FROM AUTHOR]

Objectives: To generate pseudo-CT (pCT) images of the pelvis from zero echo time (ZTE) MR sequences and compare them to conventional CT. Methods: Ninety-one patients were prospectively scanned with CT and MRI including ZTE sequences of the pelvis. Eleven ZTE image volumes were excluded due to implants and severe B1 field inhomogeneity. Out of the 80 data sets, 60 were used to train and update a deep learning (DL) model for pCT image synthesis from ZTE sequences while the remaining 20 cases were selected as an evaluation cohort. CT and pCT images were assessed qualitatively and quantitatively by two readers. Results: Mean pCT ratings of qualitative parameters were good to perfect (2–3 on a 4-point scale). Overall intermodality agreement between CT and pCT was good (ICC = 0.88 (95% CI: 0.85–0.90); p < 0.001) with excellent interreader agreements for pCT (ICC = 0.91 (95% CI: 0.88–0.93); p < 0.001). Most geometrical measurements did not show any significant difference between CT and pCT measurements (p > 0.05) with the exception of transverse pelvic diameter measurements and lateral center-edge angle measurements (p = 0.001 and p = 0.002, respectively). Image quality and tissue differentiation in CT and pCT were similar without significant differences between CT and pCT CNRs (all p > 0.05). Conclusions: Using a DL-based algorithm, it is possible to synthesize pCT images of the pelvis from ZTE sequences. The pCT images showed high bone depiction quality and accurate geometrical measurements compared to conventional CT. Critical relevance statement: pCT images generated from MR sequences allow for high accuracy in evaluating bone without the need for radiation exposure. Radiological applications are broad and include assessment of inflammatory and degenerative bone disease or preoperative planning studies. Key Points: pCT, based on DL-reconstructed ZTE MR images, may be comparable with true CT images. Overall, the intermodality agreement between CT and pCT was good with excellent interreader agreements for pCT. Geometrical measurements and tissue differentiation were similar in CT and pCT images. [ABSTRACT FROM AUTHOR]

Extramedullary devices are used extensively to stabilize fractures in long bones. The type of pin–bone anchorage is a determining factor in fixation properties, which differ between mono-cortical and bi-cortical stabilizations. This computational study compares the effects of mono-cortical and bi-cortical pins of a unilateral uniplanar external fixator on the construct stiffness, the early phase of bone healing, and pin loosening. Eight finite element models were established for a simple transverse tibia fracture, treated with a unilateral uniplanar external fixator with surgical variations in the pin-bone anchorage. Each model was subjected to a partial body weight, and axial stiffness was calculated. A deviatoric strain-based mechano-regulation algorithm was applied, and tissue differentiation in the callus was predicted. Finally, a strain-based failure criterion was employed to assess the risk of pin loosening. The axial stiffnesses of bi-cortical structures were slightly larger than the results of the mono-cortical sets. Regardless of the number of pins, bi-cortical systems produce a more uniform distribution of differentiated tissue than the corresponding mono-cortical constructs. Finally, both mono-cortical and bi-cortical groups held the critical strains of the pin–bone interface within the acceptable ranges and provided a protected construct against the risk of pin loosening. Based on the findings of this study, mono-cortical pins could be considered potential alternatives to bi-cortical fixations at the early stage of healing. Nevertheless, successful management of diaphyseal fracture through mono-cortical fixation needs to be assessed in further studies over the full period of healing. [ABSTRACT FROM AUTHOR]