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Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, and its etiology remains unclear. Presently, main drugs such as aminosalicylic acid, glucocorticoid, immunosuppressive and biological agents are employed to treat IBD. However, because of the long-term use of medication, it adversely affects other human organs. Therefore, natural bioactive compounds are applied as supplements or alternative drugs to alleviate IBD. As a kind of plant natural compounds with strong antioxidant and anti-inflammatory activities, carotenoids have exhibited potent effects in reducing intestinal inflammation. However, direct oral administration of carotenoids might cause the low specificity of inflammatory sites, which is attributed to its poor aqueous solubility and limited stability. The construction of nutrient delivery system has become an effective, efficient and dependable means. This review summarizes the delivery systems loaded with carotenoids, explores their mechanism and applications in alleviating IBD, and aims to provide corresponding theoretical references for developing novel delivery systems and their practical prospects in IBD. [ABSTRACT FROM AUTHOR]

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Middle East respiratory syndrome coronavirus (MERS-CoV) and the pangolin MERS-like coronavirus MjHKU4r-CoV-1 employ dipeptidyl peptidase 4 (DPP4) as an entry receptor. MjHKU4r-CoV-1 could infect transgenic mice expressing human DPP4. To understand the mechanism of MjHKU4r-CoV-1 entry into cells, we determined the crystal structures of the receptor binding domain (RBD) of MjHKU4r-CoV-1 spike protein bound to human DPP4 (hDPP4) and Malayan pangolin DPP4 (MjDPP4), respectively. The overall hDPP4-binding mode of MjHKU4r-CoV-1 RBD is similar to that of MERS-CoV RBD. MjHKU4r-CoV-1 RBD shows higher binding affinity to hDPP4 compared to the bat MERS-like coronavirus Ty-BatCoV-HKU4. Via swapping residues between MjHKU4r-CoV-1 RBD and Ty-BatCoV-HKU4 RBD, we identified critical determinants on MjHKU4r-CoV-1 that are responsible for virus usage of hDPP4. Our study suggests that MjHKU4r-CoV-1 is more adapted to the human receptor compared to the bat HKU4 coronavirus and highlights the potential of virus emergence into the human population. Author summary: MjHKU4r-CoV-1 is a MERS-like coronavirus isolated in Malayan pangolins. As a pangolin coronavirus that evolves from its counterparts in bats, MjHKU4r-CoV-1 could use bat, pangolin or human dipeptidyl peptidase 4 (DPP4) as an entry receptor. MjHKU4r-CoV-1 is infectious in human organs and human DPP4 transgenic mice as well and therefore shows the risk of infecting humans. However, the mechanism of receptor recognition by MjHKU4r-CoV-1 is not clear, which is important for evaluating the zoonotic potential of the virus. Here, we showed that MjHKU4r-CoV-1 entered human DPP4 expressing cells more efficiently than its bat progenitor, Ty-BatCoV-HKU4. We further determined the crystal structures of MjHKU4r-CoV-1 receptor binding domains (RBDs) complexed with human DPP4 and pangolin DPP4, respectively. Based on structure guided mutagenesis studies, we identified key residues on MjHKU4r-CoV-1 that determined the virus preference for human DPP4 receptor. Therefore, our study implies that the pangolin coronavirus MjHKU4r-CoV-1 have a risk of emergence into the human population. Future surveillance studies of pangolins and other animals are necessary to determine the transmission chains and zoonotic potential of MjHKU4r-CoV-1. [ABSTRACT FROM AUTHOR]

Introduction: ABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi KT. However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR. Methods: Eculizumab treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively. Results: The initial titers of anti-ABO antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells. Conclusions: Short-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy. [ABSTRACT FROM AUTHOR]

Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as "digital twins" for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology. [ABSTRACT FROM AUTHOR]

COVID-19 is an RNA virus belonging to the SARS family of viruses and includes a wide range of symptoms along with effects on other body organs in addition to the respiratory system. The high speed of transmission, severe complications, and high death rate caused scientists to focus on this disease. Today, many different investigation types are performed on COVID-19 from various points of view in the literature. This review summarizes most of them to provide a useful guideline for researchers in this field. After a general introduction, this review is divided into three parts. In the first one, various transmission ways COVID-19 are classified and explained in detail. The second part reviews the used biological samples for the detection of virus and the final section describes the various methods reported for the diagnosis of COVID-19 in various biological matrices. [ABSTRACT FROM AUTHOR]

While our understanding of pain is rapidly growing, some areas of pain research are lagging behind. This article discusses two current and inter-related gaps in knowledge that are in need of addressing: first, the connections between “brain” and “body” components of pain; and second, the process of endogenous pain resolution. Historical reasons for these research gaps are discussed and solutions are outlined based on an integrative, whole person research approach. These include comprehensive mapping of the mechanosensory and nociceptive innervation of deep tissues; developing objective, non-invasive measurements to quantify the metabolic, structural and mechanical components of the peripheral tissue environment; integrating our understanding of pain pathophysiology, across whole organs and whole body, as well as across bio-psycho-social domains; and understanding the interplay of nervous system and peripheral tissue mechanisms that promote the endogenous resolution of pain and prevent its acute-to-chronic transition. Current NIH-led efforts in these areas are outlined, including several studies within the NIH HEAL (or Help End Addition Long Term) initiative and the National Center for Complementary and Integrative Health’s strategic priorities in whole person research. [ABSTRACT FROM AUTHOR]

A range of investigative practices to aid explosive-related death investigations currently exist, although the use of histopathological bone samples to diagnose blast exposure and the distance of individuals from the blast source has not been previously reported. Forensic histopathology has been used effectively on soft tissue samples to define blast-related injuries effectively, analysing human organs such as the lungs, brain, liver, and skeletal muscles, providing important and useful forensic pathology interpretations. However, no studies currently exist examining the post-blast histological changes in human or animal bones subjected to blasts for forensic pathology practice, despite the opportunity that hard tissue bone samples present, given their significantly lower rate of decomposition over soft tissue. This study presents the first evidence-based findings on the post-blast histological changes in three animal bones when exposed to close-range chemical detonation (C4). The study's qualitative findings highlight critical changes in the tissue architecture of three different animal bone sources due to blast effects with range from the blast source. This emphasises the potential use of histopathological bone sample analysis in future blast-related death investigations, while providing ideas to further explore this work using larger-scale experiments and post-blast case studies in aid of applying this work to human samples and forensic pathology practice. [ABSTRACT FROM AUTHOR]

In England, Wales, and Northern Ireland, people can choose to donate their bodies post-mortem to Medical School Anatomy Units. The body donation (BD) process is facilitated by anatomy unit staff (AUS). However, little is known about the extent and nature of AUS work with families, including when a body cannot be accepted. To address this gap, this paper draws on data from an ethnographic study, including a survey of 15 anatomy units (AUs) in England and Northern Ireland, a case study of one AU, 20 semi-structured interviews with 31 AUS and document analysis. We reveal the number of bodies (878) that are refused across AUs and examine how AUS deal with refusals. We argue that activities around refusals constitutes 'over and above' work for AUS, as it goes beyond their expected role. We suggest that this is done out of a duty of care, and is related to the discomfort of refusing the BD gift. Attention is given to the 'over and above' work of the AUS which allows for an exploration of gift relationships and emotion management in a new arena. We conclude with recommendations to address the lack of recognition and training around AUS refusal work. [ABSTRACT FROM AUTHOR]

Infants are sensitive to distortions to the global configurations of bodies by 3.5 months of age, suggesting an early onset of body knowledge. It is unclear, however, whether such sensitivity indicates knowledge of the location of specific body parts or solely reflects sensitivity to the overall gestalt of bodies. This study addressed this issue by examining whether, like adults, infants attend to specific locations where body parts have been reorganized. Results show that adults and 5‐month‐olds, but not 3.5‐month‐olds, allocated more attention to the body joint areas (e.g., where the arm connects to the shoulder) that were reorganized versus ones that were typical. To examine whether this kind of processing is driven by low‐level features, 5‐month‐olds were tested on images in which the head was removed. Infants no longer exhibited differential scanning of typical versus reorganized bodies. Results suggest that 5‐month‐olds are sensitive to the location of body parts, thereby demonstrating adult‐like response patterns consistent with early expertise in body processing. The contrasting failure of 3.5‐month‐olds to exhibit sensitivity to the reorganization suggests a developmental change between these ages. [ABSTRACT FROM AUTHOR]

Introduction: CEP-37440 was synthesized and supplied by the research and development division of Teva Branded Pharmaceutical Products (West Chester, PA, United States). CEP-37440 represents a newly developed compound that exhibits selectivity inhibition of Focal Adhesion Kinase and Anaplastic Lymphoma Kinase FAK/ALK receptors, demonstrating novel characteristics as an orally active inhibitor. The simultaneous inhibition of ALK and FAK can effectively address resistance and enhance the therapeutic efficacy against tumors through a synergistic mechanism. Methods: The objective of this research was to create an LC-MS/MS method that is precise, efficient, environmentally friendly, and possesses a high level of sensitivity for the quantification of CEP-37440 in human liver microsomes (HLMs). The aforementioned approach was subsequently employed to evaluate the metabolic stability of CEP-37440 in HLMs in an in vitro setting. The validation procedures for the LC-MS/MS analytical method in the HLMs were performed following the bio-analytical method validation guidelines set out by the US-FDA. The AGREE program was utilized to assess the ecological impacts of the current LC-MS/MS methodology. Results and Discussion: The calibration curve linearity was seen in the range of 1–3000 ng/mL. The inter-day accuracy (% RE) exhibited a range of −2.33% to 3.22%, whilst the intra-day accuracy demonstrated a range of −4.33% to 1.39%. The inter-day precision (% RSD) exhibited a range of 0.38% to 3.60%, whilst the intra-day precision demonstrated a range of 0.16% to 6.28%. The determination of the in vitro half-life (t1/2) and moderate intrinsic clearance (Clint) of CEP-37440 yielded values of 23.24 min and 34.74 mL/min/kg, respectively. The current manuscript is considered the first analytical study for CEP-37440 quantification with the application to metabolic stability assessment. These results suggest that CEP-37440 can be categorized as a pharmaceutical agent with a moderate extraction ratio. Consequently, it is postulated that the administration of CEP-37440 to patients may not lead to the accrual of dosages within the human organs. According to in silico P450 metabolic and DEREK software, minor structural alterations to the ethanolamine moiety or substitution of the group in drug design have the potential to enhance the metabolic stability and safety profile of novel derivatives in comparison to CEP-37440. [ABSTRACT FROM AUTHOR]

Background: Cancer cells evolve under unique functional adaptations that unlock transcriptional programs embedded in adult stem and progenitor-like cells for progression, metastasis, and therapeutic resistance. However, it remains challenging to quantify the stemness-aware cell state of a tumor based on its gene expression profile. Methods: We develop a developmental-status-aware transcriptional decomposition strategy using single-cell RNA-sequencing-derived tissue-specific fetal and adult cell signatures as anchors. We apply our method to various biological contexts, including developing human organs, adult human tissues, experimentally induced differentiation cultures, and bulk human tumors, to benchmark its performance and to reveal novel biology of entangled developmental signaling in oncogenic processes. Results: Our strategy successfully captures complex dynamics in developmental tissue bulks, reveals remarkable cellular heterogeneity in adult tissues, and resolves the ambiguity of cell identities in in vitro transformations. Applying it to large patient cohorts of bulk RNA-seq, we identify clinically relevant cell-of-origin patterns and observe that decomposed fetal cell signals significantly increase in tumors versus normal tissues and metastases versus primary tumors. Across cancer types, the inferred fetal-state strength outperforms published stemness indices in predicting patient survival and confers substantially improved predictive power for therapeutic responses. Conclusions: Our study not only provides a general approach to quantifying developmental-status-aware cell states of bulk samples but also constructs an information-rich, biologically interpretable, cell-state panorama of human cancers, enabling diverse translational applications. [ABSTRACT FROM AUTHOR]

The liver is the largest solid organ in the body and is primarily composed of hepatocytes (HCs), endothelial cells (ECs), Kupffer cells (KCs), and hepatic stellate cells (HSCs), which spatially interact and cooperate with each other to maintain liver homeostasis. However, the complexity and molecular mechanisms underlying the crosstalk between these different cell types remain to be revealed. Here, we generated mice with conditional deletion of Gdf2 (also known as Bmp9) and Bmp10 in different liver cell types and demonstrated that HSCs were the major source of GDF2 and BMP10 in the liver. Using transgenic ALK1 (receptor for GDF2 and BMP10) reporter mice, we found that ALK1 is expressed on KCs and ECs other than HCs and HSCs, and GDF2 and BMP10 secreted by HSCs promote the differentiation of KCs and ECs and maintain their identity. Pdgfb expression was significantly upregulated in KCs and ECs after Gdf2 and Bmp10 deletion, ultimately leading to HSCs activation and liver fibrosis. ECs express several angiocrine factors, such as BMP2, BMP6, Wnt2, and Rspo3, to regulate HC iron metabolism and metabolic zonation. We found that these angiocrine factors were significantly decreased in ECs from Gdf2/Bmp10HSC-KO mice, which further resulted in liver iron overload and disruption of HC zonation. In summary, we demonstrated that HSCs play a central role in mediating liver cell-cell crosstalk via the production of GDF2 and BMP10, highlighting the important role of intercellular interaction in organ development and homeostasis. [ABSTRACT FROM AUTHOR]

Organoids are emerging as a powerful tool to investigate complex biological structures in vitro. Vascularization of organoids is crucial to recapitulate the morphology and function of the represented human organ, especially in the case of the kidney, whose primary function of blood filtration is closely associated with blood circulation. Current in vitro microfluidic approaches have only provided initial vascularization of kidney organoids, whereas in vivo transplantation to animal models is problematic due to ethical problems, with the exception of xenotransplantation onto a chicken chorioallantoic membrane (CAM). Although CAM can serve as a good environment for vascularization, it can only be used for a fixed length of time, limited by development of the embryo. Here, we propose a novel lab on a chip design that allows organoids of different origin to be cultured and vascularized on a CAM, as well as to be transferred to in vitro conditions when required. Mouse embryonic kidneys cultured on the CAM showed enhanced vascularization by intrinsic endothelial cells, and made connections with the chicken vasculature, as evidenced by blood flowing through them. After the chips were transferred to in vitro conditions, the vasculature inside the organoids was successfully maintained. To our knowledge, this is the first demonstration of the combination of in vivo and in vitro approaches applied to microfluidic chip design. [ABSTRACT FROM AUTHOR]

Synchrotron-based tomographic phase-contrast X-ray imaging (SRµCT or SRnCT) is a versatile isotropic three-dimensional imaging technique that can be used to study biological samples spanning from single cells to human-sized specimens. SRµCT and SRnCT take advantage of the highly brilliant and coherent X-rays produced by a synchrotron light source. This enables fast data acquisition and enhanced image contrast for soft biological samples owing to the exploitation of phase contrast. In this Review, we provide an overview of the basics behind the technique, discuss its applications for biologists and provide an outlook on the future of this emerging technique for biology.We introduce the latest advances in the field, such as whole human organs imaged with micron resolution, using X-rays as a tool for virtual histology and resolving neuronal connections in the brain. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a crucial role in movement, metabolism, and energy homeostasis. As the most metabolically active endocrine organ in the body, it has recently attracted widespread attention. Skeletal muscle possesses the ability to release adipocytokines, bioactive peptides, small molecular metabolites, nucleotides, and other myogenic cell factors; some of which have been shown to be encapsulated within small vesicles, particularly exosomes. These skeletal muscle exosomes (SKM-Exos) are released into the bloodstream and subsequently interact with receptor cell membranes to modulate the physiological and pathological characteristics of various tissues. Therefore, SKM-Exos may facilitate diverse interactions between skeletal muscle and other tissues while also serving as biomarkers that reflect the physiological and pathological states of muscle function. This review delves into the pivotal role and intricate molecular mechanisms of SKM-Exos and its derived miRNAs in the maturation and rejuvenation of skeletal muscle, along with their intercellular signaling dynamics and physiological significance in interfacing with other tissues. [ABSTRACT FROM AUTHOR]

The serine/threonine/tyrosine kinase 1 (STYK1) is a receptor protein-tyrosine kinase (RPTK)-like molecule that is detected in several human organs. STYK1 plays an important role in promoting tumorigenesis and metastasis in various cancers. By analyzing the expression of RTKs in immune cells in the database of 2013 Immunological Genome Project, we found that STYK1 was principally expressed in NK cells. In order to investigate the function of STYK1, we used CRISPR/Cas9 technology to generate STYK1-deleted mice, we found STYK1 deletion mice have normal number, development, and function of NK cells in spleen and bone marrow in tumor-free resting state. To examine the tumor surveillance of STYK1 in vivo, we utilized a variety of tumor models, including NK cell-specific target cell (ß2M and RMA-S) clearance experiments in vivo, subcutaneous and intravenous injection of B16F10 melanoma model, and the spontaneous breast cancer model MMTV-PyMT. Surprisingly, we discovered that deletion of the oncogenic STYK1 promoted the four-model tumor progression, and we observed a reduction of NK cell accumulation in the tumor tissues of STYK1 deletion mice compared to WT mice. In order to study the mechanism of STYK1 in NK, RNA sequence of STYK1−/− and WT NK have unveiled a disparity in the signaling pathways linked to migration and adhesion in STYK1−/− NK cells. Further analysis of chemokine receptors associated with NK cell migration revealed that STYK1-deficient NK cells exhibited a significant reduction in CCR2 expression. The STYK1 expression was negatively associated with tumor progression in glioma patients. Overall, our study found the expression of STYK1 in NK cell mediates NK cell anti-tumor response through regulating CCR2 and infiltrating into tumor tissue. [ABSTRACT FROM AUTHOR]

As a form of dementia, Alzheimer's disease (AD) suffers from no efficacious cure, yet AD treatment is still imperative, as it ameliorates the symptoms or prevents it from deteriorating or maintains the current status to the longest extent. The human brain is the most sensitive and complex organ in the body, which is protected by the blood–brain barrier (BBB). This yet induces the difficulty in curing AD as the drugs or nanomaterials that are much inhibited from reaching the lesion site. Thus, BBB crossing capability of drug delivery system remains a significant challenge in the development of neurological therapeutics. Fortunately, nano‐enabled delivery systems possess promising potential to achieve multifunctional diagnostics/therapeutics against various targets of AD owing to their intriguing advantages of nanocarriers, including easy multifunctionalization on surfaces, high surface‐to‐volume ratio with large payloads, and potential ability to cross the BBB, making them capable of conquering the limitations of conventional drug candidates. This review, which focuses on the BBB crossing ability of the multifunctional nanomaterials in AD diagnosis and treatment, will provide an insightful vision that is conducive to the development of AD‐related nanomaterials. [ABSTRACT FROM AUTHOR]

Almost all implantable electronic medical devices (IEMDs) are powered by bulky Li‐ion batteries (LIBs), limiting their miniaturization and lifespan advancements. In addition, LIBs contain toxic materials and flammable electrolytes that are dangerous if they leak into human organs. In this context, there is an urgent need to explore new approaches and concepts that can address the critical challenges of designing novel electrochemical energy storage systems and gain a mechanistic understanding of the phenomena taking place in diverse scenarios. This review summarizes recent advancements in biocompatible supercapacitors (B‐SCs) as a power source for various IEMDs, offering a potential solution to these challenges. Different types of IEMDs and their power requirements are briefly discussed, along with challenges arising from energy storage systems and their applications in IEMDs. Given the importance of electrode materials in determining the electrochemical performance of B‐SCs in terms of energy and power densities, different electrode materials and their developments are systematically reviewed. Finally, new insights are offered into potential opportunities and future prospects for the rational design of next‐generation B‐SCs. [ABSTRACT FROM AUTHOR]

Porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation have garnered attention, but both face technical challenges. Interspecies chimeric organ production using human iPSCs shows promise in overcoming these challenges. Our group successfully generated chimeric renal organoids using human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology is limited to rodents. Therefore, this study focused on producing human-pig chimeric renal organoids, as pigs are the most promising species for xenotransplantation. Modification of existing culture systems enables continuous renal development in both species, resulting in the successful creation of human-pig chimeric renal organoids. Moreover, this method can be applied to generate humanized xenogeneic kidneys for future clinical applications. This study provides evidence that optimizing culture conditions enables the early-stage kidney development beyond species barriers, thus laying the foundation for accelerating research on humanized xenogeneic kidney fabrication for clinical purposes. Creation of chimeric renal organoids using human iPSC technology with fetal pig kidneys demonstrates inter-species coexistence and codevelopment in early kidney development, paving the way for humanized xenogeneic kidney creation for clinical use. [ABSTRACT FROM AUTHOR]

Liver cancer a leading cause of cancer-related deaths worldwide, yet understanding of its development mechanism remains limited, and treatment barriers present substantial challenges. Owing to the heterogeneity of tumors, traditional 2D culture models are inadequate for capturing the complexity and diversity of tumor biology and understanding of the disease. Organoids have garnered considerable attention because of their ability to self-renew and develop functional structures in vitro that closely resemble those of human organs. This review explores the history of liver organoids, their cellular origins, techniques of constructing tumor microenvironments that recapitulate liver cancer organoids, and the biological and clinical applications of liver and liver cancer organoids and explores the current challenges related to liver cancer organoid applications and potentially valuable solutions, with the aim of facilitating the construction of in vitro clinical models of liver cancer therapeutic research. [ABSTRACT FROM AUTHOR]

Resonance and synchronized rhythm are significant phenomena observed in dynamical systems in nature, particularly in biological contexts. These phenomena can either enhance or disrupt system functioning. Numerous examples illustrate the necessity for organs within the human body to maintain their rhythmic patterns for proper operation. For instance, in the brain, synchronized or desynchronized electrical activities can contribute to neurodegenerative conditions like Huntington's disease. In this paper, we utilize the well-established Hodgkin–Huxley (HH) model, which describes the propagation of action potentials in neurons through conductance-based mechanisms. Employing a "data-driven" approach alongside the outputs of the HH model, we introduce an innovative technique termed "dynamic entrainment." This technique leverages deep learning methodologies to dynamically sustain the system within its entrainment regime. Our findings show that the results of the dynamic entrainment technique match with the outputs of the mechanistic (HH) model. [ABSTRACT FROM AUTHOR]

The article in Clinical & Translational Discovery identifies a rare population of metallothionein-expressing macrophages present in all vital human organs. Using single-cell RNA sequencing data, the study characterizes these macrophages in the liver, kidney, and lung, highlighting their gene expression patterns and potential functional roles. Immunohistochemistry techniques confirm the presence of these macrophages in human liver tissue, suggesting a role in neoangiogenesis. The research sets the stage for further studies on the functional role of these macrophages in tissue homeostasis and remodeling. [Extracted from the article]

This study investigates the forces exerted on organs during swallowing, specifically focusing on identifying forces other than those resulting from direct organ contact. Using a swallowing simulator based on the moving particle method, we simulated the swallowing process of healthy individuals upon the ingestion of thickened foods, which were simulated as shear‐thinning flow without yield stress. We extracted the resultant force vectors acting on the organs and shape of the bolus at each time interval. The simulation results confirmed that the bolus originates from tongue movement and is transferred between the oral cavity and pharynx, with each organ's coordinated movements with the tongue occurring at their respective positions, as indicated by the balance of the resultant force vectors. Utilizing the information about the resultant force vectors obtained through simulations, we calculated the physical parameters of impulse, energy, and power. The variations in these physical parameters were aligned with the behaviors of both the biological system and the food bolus during swallowing. The force values calculated from the simulations closely approximate the theoretical values. Furthermore, the forces calculated from the simulations were relatively smaller than the force values derived from pressure information, such as that from high‐resolution manometry and tongue pressure sensors. This difference can be attributed to the simulations extracting only the forces exerted on the organ by the food bolus. Force information on organs has the potential to provide a new interpretation of conventional mechanical indicators such as manometry and tongue pressure sensors. [ABSTRACT FROM AUTHOR]

Organogenesis, the phase of embryonic development that starts at the end of gastrulation and continues until birth is the critical process for understanding cellular differentiation and maturation during organ development. The rapid development of single‐cell transcriptomics technology has led to many novel discoveries in understanding organogenesis while also accumulating a large quantity of data. To fill this gap, OrganogenesisDB (http://organogenesisdb.com/), which is a comprehensive database dedicated to exploring cell‐type identification and gene expression dynamics during organogenesis, is developed. OrganogenesisDB contains single‐cell RNA sequencing data for more than 1.4 million cells from 49 published datasets spanning various developmental stages. Additionally, 3324 cell markers are manually curated for 1120 cell types across 9 human organs and 4 mouse organs. OrganogenesisDB leverages various analysis tools to assist users in annotating and understanding cell types at different developmental stages and helps in mining and presenting genes that exhibit specific patterns and play key regulatory roles during cell maturation and differentiation. This work provides a critical resource and useful tool for deciphering cell lineage determination and uncovering the mechanisms underlying organogenesis. [ABSTRACT FROM AUTHOR]

The bone marrow represents one of the largest organs in the body, with a relevant metabolic role that continues to be investigated. Numerous studies have focused on marrow adipose tissue (MAT). Evidence indicates that the bone marrow adipocytes do not only work as storage tissue but also consist of endocrine and paracrine cells, with the potential to contribute to local and systemic metabolism. MAT plays a role in bone health through its interaction with the other components of bone. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established or understood relationship with bone health. This article surveys the literature on the relationship of bone marrow and metabolic disorders, and how it is being studied using imaging techniques, with a special focus on bone health. [ABSTRACT FROM AUTHOR]

High-throughput transcriptomics (HTTr) is increasingly being used to identify molecular targets of chemicals that can be linked to adverse outcomes. Cell proliferation (CP) is an important key event in chemical carcinogenesis. Here, we describe the construction and characterization of a gene expression biomarker that is predictive of the CP status in human and rodent tissues. The biomarker was constructed from 30 genes known to be increased in expression in prostate cancers relative to surrounding tissues and in cycling human MCF-7 cells after estrogen receptor (ER) agonist exposure. Using a large compendium of gene expression profiles to test utility, the biomarker could identify increases in CP in (i) 308 out of 367 tumor vs. normal surrounding tissue comparisons from 6 human organs, (ii) MCF-7 cells after activation of ER, (iii) after partial hepatectomy in mice and rats, and (iv) the livers of mice and rats after exposure to nongenotoxic hepatocarcinogens. The biomarker identified suppression of CP (i) under conditions of p53 activation by DNA damaging agents in human cells, (ii) in human A549 lung cells exposed to therapeutic anticancer kinase inhibitors (dasatinib, nilotnib), and (iii) in the mouse liver when comparing high levels of CP at birth to the low background levels in the adult. The responses using the biomarker were similar to those observed using conventional markers of CP including PCNA, Ki67, and BrdU labeling. The CP biomarker will be a useful tool for interpretation of HTTr data streams to identify CP status after exposure to chemicals in human cells or in rodent tissues. [ABSTRACT FROM AUTHOR]

Neuromodulators act on multiple timescales to affect neuronal activity and behavior. They function as synaptic fine-tuners and master coordinators of neuronal activity across distant brain regions and body organs. While much research on neuromodulation has focused on roles in promoting features of wakefulness and transitions between sleep and wake states, the precise dynamics and functions of neuromodulatory signaling during sleep have received less attention. This review discusses research presented at our minisymposium at the 2024 Society for Neuroscience meeting, highlighting how norepinephrine, dopamine, and acetylcholine orchestrate brain oscillatory activity, control sleep architecture and microarchitecture, regulate responsiveness to sensory stimuli, and facilitate memory consolidation. The potential of each neuromodulator to influence neuronal activity is shaped by the state of the synaptic milieu, which in turn is influenced by the organismal or systemic state. Investigating the effects of neuromodulator release across different sleep substates and synaptic environments offers unique opportunities to deepen our understanding of neuromodulation and explore the distinct computational opportunities that arise during sleep. Moreover, since alterations in neuromodulatory signaling and sleep are implicated in various neuropsychiatric disorders and because existing pharmacological treatments affect neuromodulatory signaling, gaining a deeper understanding of the less-studied aspects of neuromodulators during sleep is of high importance. [ABSTRACT FROM AUTHOR]

Myiasis is a disease caused by fly larvae from the Diptera order settling in various tissues and organs of humans or animals. To report the diagnosis of myiasis larvae invading the oral and nasal cavities of patients in the management of intensive care units and to draw attention to the poor hygiene situation. A 78-year-old male patient diagnosed with cancer and a 93-year-old male patient diagnosed with ischemic cerebrovascular disease were followed up in the intensive care unit. On the 21st day of the cancer patient's hospitalization, eight larvae were removed from the oral cavity. In the first month of the other patient's hospitalization, six larvae were seen in the patient's nasal osteum near the feeding tube. A clinical diagnosis of myiasis was made and the larvae were initially manually removed for treatment, followed by medication. In conclusion, myiasis is a rare condition, but good hygiene, correct diagnosis, and treatment are necessary to prevent further harm to those who have risk factors such as immunosuppression, poor hygiene, malnutrition, diabetes, and peripheral vascular disease, particularly those who are hospitalized. [ABSTRACT FROM AUTHOR]

In order to inspect the interior of hollow organs or cavities in the human body, endoscopes are frequently employed in medicine. Over time, they have undergone substantial evolution and are now able to offer invaluable diagnostic data. The non‐invasive identification of tissue abnormalities with subcellular resolution or real‐time biochemical information is made possible by novel endoscopic optical diagnostic methods. These methods provide benefits in terms of detection, characterization, and confirmation while challenging conventional histology. An investigation is conducted on a magnetized ternary nanofluid to analyze its heat production characteristics in a heated flow scenario between two curved conduits that are peristaltic and experience sinusoidal fluctuations. In this study, the use of a new peristaltic endoscope inside a curved conduit is examined, with a specific focus on evaluating the flowing behavior and heat transference attributes. The use of a versatile and innovative endoscope equipped with peristaltic locomotion proves to be a superior approach for conducting endoscopic procedures on intricate mechanical systems. Furthermore, this advanced endoscope offers enhanced comfort for patients undertaking endoscopy of various human parts. A detailed mathematical model has been constructed to fully assess the flowing and heat transference study of this innovative endoscope using the main unsteady regulating formulas like impetus, Maxwell, and heat in their general form, then transformed to a non‐dimensional system with the assumption of a low Reynold's number and wavelength. Mathematica software was used to conduct precise and methodical calculations, enabling the acquisition of both accurate mathematical results and graphical representations. According to certain findings, the conduit is more influenced by the magnetized force, and the pressure rate over the channel width changes from a linear relationship to a sharp curve that ends in a small peak. Additionally, when utilizing different kinds of nanoparticles, there is a noticeable increase in the pressure gradient's magnitude. [ABSTRACT FROM AUTHOR]

Nonprocessed foodstuffs of plant origin, especially whole-grain cereals, are considered to be health-promoting components of the human diet. While most of their well-studied effects derive from their high fiber content and low glycemic index, the presence of underrated phenolic phytonutrients has recently been brought to the attention of nutritionists. In this review, we report and discuss findings on the sources and bioactivities of 3,5-dihydroxybenzoic acid (3,5-DHBA), which is both a direct dietary component (found, e.g., in apples) and, more importantly, a crucial metabolite of whole-grain cereal-derived alkylresorcinols (ARs). 3,5-DHBA is a recently described exogenous agonist of the HCAR1/GPR81 receptor. We concentrate on the HCAR1-mediated effects of 3,5-DHBA in the nervous system, on the maintenance of cell stemness, regulation of carcinogenesis, and response to anticancer therapy. Unexpectedly, malignant tumors take advantage of HCAR1 expression to sense 3,5-DHBA to support their growth. Thus, there is an urgent need to fully identify the role of whole-grain-derived 3,5-DHBA during anticancer therapy and its contribution in the regulation of vital organs of the body via its specific HCAR1 receptor. We discuss here in detail the possible consequences of the modulatory capabilities of 3,5-DHBA in physiological and pathological conditions in humans. [ABSTRACT FROM AUTHOR]

There are controversial findings on how projectile penetration into the human tissue can induce tissue damage. The evidence from recent experimental investigations has explained the related underlying mechanisms. To understand and simulate the exact biomechanical mechanisms of projectile penetration-induced tissue damage, we evaluated effects of two-dimensional (2D) transient stress wave propagation of 2D-functionally graded material (FGM, radial and circumferential inhomogeneity) in an infinite hollow cylinder. A periodic radial and circumferential material gradation fluctuating a constant value has been considered as the effective material properties, across the cylinder wall and the problem has been solved by implementing the graded finite element method with nonlinear Lagrangian shape functions. In contrast with other researches, the stress wave propagation for $ r $ r and $ \theta $ θ -inhomogeneity is different compared to the case in which the $ r $ r or $ \theta $ θ -inhomogeneity has been considered, separately. Moreover, this example resembles the bullet penetration in human tissue that produces stress wave propagation, resulting in unintentional trauma in human organs. For the case of 1D-FGM ( $ r $ r – inhomogeneity), the responses are pulse-like and symmetric. Finally, due to shear waves, the $ \theta $ θ -inhomogeneity has more visible effect on the stress wave propagation than $ r $ r – inhomogeneity due to shear waves, especially when the pulse collapses. [ABSTRACT FROM AUTHOR]

TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases. [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]

FFA4 has gained interest in recent years since its deorphanization in 2005 and the characterization of the Free Fatty Acids receptors family for their therapeutic potential in metabolic disorders. The expression of FFA4 (also known as GPR120) in numerous organs throughout the human body makes this receptor a highly potent target, particularly in fat sensing and diet preference. This offers an attractive approach to tackle obesity and related metabolic diseases. Recent cryo‐EM structures of the receptor have provided valuable information for a potential active state although the previous studies of FFA4 presented diverging information. We performed molecular docking and molecular dynamics simulations of four agonist ligands, TUG‐891, Linoleic acid, α‐Linolenic acid, and Oleic acid, based on a homology model. Our simulations, which accumulated a total of 2 μs of simulation, highlighted two binding hotspots at Arg992.64 and Lys293 (ECL3). The results indicate that the residues are located in separate areas of the binding pocket and interact with various types of ligands, implying different potential active states of FFA4 and a highly adaptable binding intra‐receptor pocket. This article proposes additional structural characteristics and mechanisms for agonist binding that complement the experimental structures. [ABSTRACT FROM AUTHOR]

Prostaglandin D2 (PGD2) levels are high in the balding areas of human scalps, and PGD2 has been found to inhibit hair growth. It is known that the inhibition of the PGD2 receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema® drug development program. In this study, we identified that the DP2 antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss. [ABSTRACT FROM AUTHOR]

Prostate cancer is a disease in which cells in the prostate, a gland in the male reproductive system below the bladder, grow out of control and, among men, it is the second-most frequently diagnosed cancer (other than skin cancer). In recent years, prostate cancer death rate has stabilized and, currently, it is the second-most frequent cause of cancer death in men (after lung cancer). Most deaths occur due to metastasis, as cancer cells from the original tumor establish secondary tumors in distant organs. For a long time, classical cell cultures and animal models have been utilized in basic and applied scientific research, including clinical applications for many diseases, such as prostate cancer, since no better alternatives were available. Although helpful in dissecting cellular mechanisms, these models are poor predictors of physiological behavior mainly because of the lack of appropriate microenvironments. Microfluidics has emerged in the last two decades as a technology that could lead to a paradigm shift in life sciences and, in particular, controlling cancer. Microfluidic systems, such as organ-on-chips, have been assembled to mimic the critical functions of human organs. These microphysiological systems enable the long-term maintenance of cellular co-cultures in vitro to reconstitute in vivo tissue-level microenvironments, bridging the gap between traditional cell cultures and animal models. Several reviews on microfluidics for prostate cancer studies have been published focusing on technology advancement and disease progression. As metastatic castration-resistant prostate cancer remains a clinically challenging late-stage cancer, with no curative treatments, we expanded this review to cover recent microfluidic applications related to prostate cancer research. The review includes discussions of the roles of microfluidics in modeling the human prostate, prostate cancer initiation and development, as well as prostate cancer detection and therapy, highlighting potentially major contributions of microfluidics in the continuous march toward eradicating prostate cancer. [ABSTRACT FROM AUTHOR]

Inner ear organoids play a crucial role in hearing research. In comparison to other animal models and 2D cell culture systems, inner ear organoids offer significant advantages for studying the mechanisms of inner ear development and exploring novel approaches to disease treatment. Inner ear organoids derived from human cells are more closely resemble normal human organs in development and function. The 3D culture system of the inner ear organoid enhances cell–cell interactions and mimics the internal environment. In this review, the progress and limitations of organoid culture methods derived from tissue‐specific progenitors and pluripotent stem cells (PSCs) are summarized, which may offer new insights into generating organoids that closely resemble the inner ear in terms of morphology and function. [ABSTRACT FROM AUTHOR]

Objective: To isolate and purify the polysaccharides from Lycium barbarum and study its in vitro antioxidant activity and in vivo anti-aging effect. Methods: Crude polysaccharides from Lycium barbarum were obtained by water extraction and alcohol precipitation, and then LBP was isolated and purified from crude polysaccharides by Sevage reagent and DEAE-52 cellulose ion exchange resin. By measuring the scavenging ability of LBP to DPPH free radical, hydroxyl radical and ABTS+ free radical, and Fe3+ reduction, the antioxidant ability of LBP in vitro was evaluated. The aging mouse model was established by D-galactose. After administration, the body weights and organ indexes of mice in each group were compared. The levels of MDA, SOD, GSH-Px and CAT in serum, liver and brain were measured. The protein expression of Nrf-2 and HO-1 in liver tissue was detected by Western blotting. Results: The content of LBP after isolation and purification was 86.64%±2.34%. The IC50 values of scavenging ability of LBP to DPPH free radical, hydroxyl radical and ABTS+ free radical were 0.2081±0.0182, 0.7132±0.0220 and 0.3646±0.0138 mg/mL, respectively. Compared with the model group, the body weights and organ indexes of the mice in positive and high dose of LBP groups were significantly increased (P<0.05 or P<0.01). The levels of SOD, CAT and GSH-Px in serum, liver and brain of mice in positive and high dose of LBP groups were significantly increased, and the level of MDA was significantly decreased (P<0.01). The expression level of Nrf-2 protein in liver tissue increased significantly except for in the low dose of LBP group (P<0.05), and the expression level of HO-1 protein increased significantly in all groups (P<0.05 or P<0.01). Conclusion: LBP from Lycium barbarum has strong antioxidant ability and certain anti-aging effect, and its mechanism may be related to Nrf-2/HO-1 signal pathway. [ABSTRACT FROM AUTHOR]

The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important to their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the fallopian tube that molecularly, functionally, and architecturally resembles the organ. Global label-free proteomics, innovative assays capturing physiological functions of the fallopian tube (i.e., oocyte transport), and whole-organ single-cell resolution mapping are used to validate these assembloids through a multifaceted platform with direct comparisons to fallopian tube tissue. These techniques converge at a unique combination of assembloid parameters with the highest similarity to the reference fallopian tube. This work establishes (i) an optimized model of the human fallopian tubes for in vitro studies of their pathophysiology and (ii) an iterative platform for customized 3D in vitro models of human organs that are molecularly, functionally, and microanatomically accurate by combining tunable assembloid and tissue mapping methods. [ABSTRACT FROM AUTHOR]

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM–cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems. [ABSTRACT FROM AUTHOR]

Amiodarone hydrochloride is an antiarrhythmic agent that is widely prescribed. However, it has serious side effects that approximately affect the whole body organs. In our study, we aimed to assess the possible effects of chronic administration of two different doses of amiodarone hydrochloride on the oxidative and inflammatory parameters as well as the histological morphology and ultrastructure of the seminiferous tubules of adult male albino rats. Forty rats were divided into four groups; Control group 1: each rat did not receive any drugs at all. Control group 2: each rat received 3 ml of 0.16% methylcellulose, orally and daily for 4 weeks. Low dose amiodarone group: each rat received 3 ml of 0.16% methylcellulose contained 3.6 mg amiodarone, orally and daily for 4 weeks. High dose amiodarone group: each rat received 3 ml of 0.16% methylcellulose contained 7.2 mg amiodarone, orally and daily for 4 weeks. Blood samples were collected for measuring serum levels of malondialdehyde, superoxide dismutase, interleukin-6 and tumor necrosis factor-alpha. Testes specimens were examined to assess the morphological changes and the level of expression of caspase-3 apoptotic marker. The results indicated that; amiodarone hydrochloride could induce a dose-dependent toxicity, causing oxidative stress, inflammation, cellular degeneration, deposition of collagen and enhanced apoptosis in the seminiferous tubules. [ABSTRACT FROM AUTHOR]

Introduction: Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection. Methods: DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed. Results: DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-kB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were upregulated in DPSC.7 cells when stimulated with C.a. Conclusions: Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-kB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections. [ABSTRACT FROM AUTHOR]

Cell‐rich spheroids have gained increasing applications due to their ability to mimic the 3D microenvironment of real tissues. Given human organ dimensions, millimeter‐sized (>1 mm) spheroids are more clinically valuable than micro‐sized ones (<500 µm). However, constructing millimeter‐sized spheroids faces the primary challenge of core necrosis due to insufficient nutrient diffusion during long‐term in vitro cultivation (>3 days). Developing rapid spheroid fabrication strategies can address the issue but remains challenging. Here, a flexible fibrin‐based platform for rapid fabrication of the spheroids is developed using a one‐step manufacturing technology. Cell‐laden fibrin hydrogels are polymerized from cell‐containing fibrinogen by thrombin‐catalyzed reactions within minutes and cultured in an agarose‐coated plate. Benefiting from the unique viscoelasticity, softness, and cell adhesion natures of fibrin, the expression levels of several cellular junction proteins are significantly upregulated compared to the scaffold‐free spheroids. As a result, cells rapidly self‐assemble into 1–15 mm‐sized spheroids within 6–24 h, accommodating high cell density (6 × 104 cells µL−1) without leakage. The spheroid formation platform is also flexible for various cell densities and cell types. Moreover, the spheroids effectively mimic the 3D tissue niches, showing promising potential in tumor drug screening with MCF‐7 spheroids and liver regeneration with HepG2 spheroids. [ABSTRACT FROM AUTHOR]

Background: Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. Methods: Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. Results: Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. Conclusions: Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo. [ABSTRACT FROM AUTHOR]

The thalamus is organized into nuclei that have distinct input and output connectivities with the cortex. Whereas first-order (FO) nuclei - also called core nuclei - relay input from sensory organs on the body surface and project to primary cortical sensory areas, higherorder (HO) nuclei - matrix nuclei - instead receive their driver input from the cortex and project to secondary and associative areas within cortico-thalamo-cortical loops. Input-dependent processes have been shown to play a crucial role in the emergence of FO thalamic neuron identity from a ground-state HO neuron identity, yet how this identity emerges during development remains unknown. Here, using single-cell RNA sequencing of the developing mouse embryonic thalamus, we show that, although they are born together, HO neurons start differentiating earlier than FO neurons. Within the FO visual thalamus, postnatal peripheral input is crucial for the maturation of excitatory, but not inhibitory, neurons. Our findings reveal different differentiation tempos and input sensitivities of HO and FO neurons, and highlight neuron type-specific molecular differentiation programs in the developing thalamus. [ABSTRACT FROM AUTHOR]

To accurately study human organ function and disease 'in the dish', it is necessary to develop reliable cell-based models that closely track human physiology. Our interest lay with the liver, which is the largest solid organ in the body. The liver is a multifunctional and highly regenerative organ; however, severe liver damage can have dire consequences for human health. A common cause of liver damage is adverse reactions to prescription drugs. Therefore, the development of predictive liver models that capture human drug metabolism patterns is required to optimise the drug development process. In our study, we aimed to identify compounds that could improve the metabolic function of stem cell-derived liver tissue. Therefore, we screened a compound library to identify additives that improved the maturity of in vitro-engineered human tissue, with the rationale that by taking such an approach, we would be able to fine-tune neonatal and adult cytochrome P450 metabolic function in stem cell-derived liver tissue. [ABSTRACT FROM AUTHOR]

Heart diseases remain one of the leading causes of morbidity and mortality worldwide, necessitating innovative diagnostic methods for early detection and intervention. An electrocardiogram (ECG) is a well-known technique for the preliminary diagnosis of heart conditions. However, it can not be used for continuous monitoring due to skin irritation. It is well known that every body organ generates a magnetic field, and the heart generates peak amplitudes of about 10 to 100 pT (measured at a distance of about 3 cm above the chest). This poses challenges to capturing such signals. This paper reviews the different techniques used to capture the heart's magnetic signals along with their limitations. In addition, this paper provides a comprehensive review of the different approaches that use the heart-generated magnetic field to diagnose several heart diseases. This research reveals two aspects. First, as a noninvasive tool, the use of the heart's magnetic field signal can lead to more sensitive advanced heart disease diagnosis tools, especially when continuous monitoring is possible and affordable. Second, its current use is limited due to the lack of accurate, affordable, and portable sensing technology. [ABSTRACT FROM AUTHOR]

Herbs, such as Aconitum carmichaeli Debeaux (ACD), have long been used as therapies, but it is difficult to identify which organs of the human body are affected by the various compounds. In this study, we predicted the organ where the drug predominantly acts using bioinformatics and verified it using transcriptomics. We constructed a computer-aided brain system network (BSN) and intestinal system network (ISN). We predicted the action points of ACD using network pharmacology (NP) analysis and predicted the dockable proteins acting in the BSN and ISN using statistical-based docking analysis. The predicted results were verified using ACD-induced transcriptome analysis. The predicted results showed that both the NP and docking analyses predominantly acted on the BSN and showed better hit rates in the hub nodes. In addition, we confirmed through verification experiments that the SW1783 cell line had more than 10 times more differentially expressed genes than the HT29 cell line and that the dominant acting organ is the brain, using network dimension spanning analysis. In conclusion, we found that ACD preferentially acts in the brain rather than in the intestine, and this multi-bioinformatics-based approach is expected to be used in future studies of drug efficacy and side effects. [ABSTRACT FROM AUTHOR]