Inhalation of Microplastics Induces Inflammatory Injuries in Multiple Murine Organs via the Toll-like Receptor Pathway.

Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.

Long-term effects of silver nanoparticles and mineral nutrition components on the photosynthetic processes, chloroplast ultrastructure and productivity of Solanum lycopersicum plants.

The effects of silver nanoparticles (AgNPs), both alone and in combination with mineral nutrients, on the growth and photosynthesis of Solanum lycopersicum plants during ontogeny were studied. The experiment involved weekly applications of 10 µmol of AgNPs for 15 weeks in a greenhouse over a summer period. A comprehensive characterization of the AgNPs was performed via TEM, ESI/EELS, and zeta potential measurements before and throughout the experiment. The activity of PSII, stomatal conductivity, photosynthesis, transpiration and respiration rates were measured, and the photosynthetic pigments, chloroplast ultrastructure, and dry and fresh masses of leaves, roots, and fruits were assessed. The results indicated that combining AgNPs with mineral nutrients increased PSII activity and the photosynthesis rate and altered the chloroplast ultrastructure. However, the use of mineral nutrients or AgNPs alone did not induce these changes. Atomic absorption spectrometry detected AgNPs in all the plant organs except the fruits. The highest fruit yield was associated with Veni Prisma®, a commercial product containing colloidal silver, which also caused desynchronized fruit maturation. This study hypothesizes that the synergistic effect of AgNPs and mineral nutrients enhances silver accumulation in chloroplasts, improving light utilization and photosynthetic efficiency, particularly under low light, thus increasing fruit quantity and dry mass. Conversely, long-term use of AgNPs alone was accompanied by silver accumulation outside the chloroplasts and did not lead to increased photosynthesis or an increase in fresh fruit mass.

Straddling the Line Between In Vitro and Ex Vivo Investigations.

Tissue engineering research fundamentally relies on experiments to advance knowledge, utilizing various models for research on both humans and animals. With scientific progress, experimental models have become increasingly complex over time. This complexity sometimes blurs the distinction between categories, making terminology less consistent. In biomedical research, three overarching terms are commonly used to characterize experimental environments: in vitro, ex vivo, and in vivo. While in vitro translates from Latin as "in glass," referring historically to experimental conditions in a test tube or petri dish, in vivo experiments occur within a living organism's natural environment. Conversely, ex vivo originates from living tissue outside its host environment while striving to maintain conditions as close to the host surroundings as possible. In the tissue engineering and regenerative medicine (TE&RM) community, there needs to be more clarity between in vitro and ex vivo terminology, with historical definitions sometimes disregarded and new terms often introduced without rigorous scientific justification. At this juncture, the question arises of when to refer to experiments as in vitro or ex vivo or whether the terms may be used synonymously in some instances. Moreover, what criteria must ex vivo experiments meet to be legitimately defined as such? This perspective is intended to address questions that would assist the TE&RM community in better understanding the differences between in vitro and ex vivo models. Impact Statement In the tissue engineering & regenerative medicine literature, the terms "in vitro" and "ex vivo" are often used interchangeably to describe experiments. This interchangeable usage can lead to a compromised interpretation of research results and, consequently, misleading scientific conclusions and teachings. This perspective aims to provide clarity on the various definitions of experimental designs. It also highlights the issue of using terms with inconsistent meanings that have origins dating back to the distant past. It's important to note that scientific definitions constantly evolve, and there is a scientifically rooted responsibility to evaluate and rethink the current state of affairs critically.

Cadmium-induced lung injury disrupts immune cell homeostasis in the secondary lymphoid organs in mice.

Cadmium (Cd) is a well-known toxic heavy metal that poses significant health risks, particularly through inhalation, smoking, and the consumption of contaminated food. Exposure to cadmium is linked to the development and exacerbation of chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). This study investigated the systemic effects of intratracheal cadmium chloride (0.5 mg/kg) instillation in C57BL/6 mice. All parameters, including inflammation assessment, lung function evaluation (using Flexi-vent), and immunophenotyping of T-cells in secondary lymphoid organs (mediastinal lymph nodes and spleen), were analyzed 14 days after cadmium exposure. The results demonstrated that cadmium exposure led to significant immune cell infiltration in bronchoalveolar lavage (BAL) fluid, altered pro-inflammatory cytokine levels, and was associated with impaired lung function, characterized by increased lung resistance and Newtonian resistance. Analysis of T-cell populations revealed no significant changes in total T-cells in mediastinal lymph nodes and spleen, but a decrease in CD4+ T-cells and an increase in CD8+ T-cells were observed. These findings suggest that cadmium disrupts T-cell homeostasis in secondary lymphoid organs. Further research is crucial to elucidate the mechanisms underlying cadmium-induced lung injury and immune dysregulation, essential for developing effective therapeutic interventions against chronic lung diseases caused by cadmium exposure.

A cascaded FAS-UNet+ framework with iterative optimization strategy for segmentation of organs at risk.

Segmentation of organs at risks (OARs) in the thorax plays a critical role in radiation therapy for lung and esophageal cancer. Although automatic segmentation of OARs has been extensively studied, it remains challenging due to the varying sizes and shapes of organs, as well as the low contrast between the target and background. This paper proposes a cascaded FAS-UNet+ framework, which integrates convolutional neural networks and nonlinear multi-grid theory to solve a modified Mumford-shah model for segmenting OARs. This framework is equipped with an enhanced iteration block, a coarse-to-fine multiscale architecture, an iterative optimization strategy, and a model ensemble technique. The enhanced iteration block aims to extract multiscale features, while the cascade module is used to refine coarse segmentation predictions. The iterative optimization strategy improves the network parameters to avoid unfavorable local minima. An efficient data augmentation method is also developed to train the network, which significantly improves its performance. During the prediction stage, a weighted ensemble technique combines predictions from multiple models to refine the final segmentation. The proposed cascaded FAS-UNet+ framework was evaluated on the SegTHOR dataset, and the results demonstrate significant improvements in Dice score and Hausdorff Distance (HD). The Dice scores were 95.22%, 95.68%, and HD values were 0.1024, and 0.1194 for the segmentations of the aorta and heart in the official unlabeled dataset, respectively. Our code and trained models are available at https://github.com/zhuhui100/C-FASUNet-plus .

Adaptation and carry over effects of extreme sporadic heat stress in Culex mosquitoes.

Mosquitoes, as temperature-sensitive ectothermic vectors, exhibit temperature-dependence. This study investigates Culex pipiens pallens (Cx. pallens) responses to abrupt temperature increases and their implications on mosquito physiology. First instar larvae (24hr post hatching) and newly enclosed adults (24hr post emergence) were separately exposed to heat shock regimes of 33 °C, 37 °C, and 42 °C for 3 days alongside a control temperature of 27 °C. Results showed that mortality was triggered at 42 °C within a day. Adult male mosquitoes were less tolerant to all temperatures than larvae and adult females (p < 0.05). Exposing larvae to constant temperatures for 3 days significantly decreased larvae's development time, growth rate and adult emergence (p < 0.05). Reproductive fitness was significantly reduced (p < 0.05) in males emerging from larvae exposed to 37 °C. Life table parameters showed significant increased mortality rate, kill power and decreased life expectancy at the embryonic stage (p < 0.05). Furthermore, heatwaves deactivated the Transient receptor protein ankyrin 1 at 37 °C (p < 0.05) in larvae but not adults. Calmodium, Heat shock protein 90, and small heat shock protein expression were significantly decreased in larvae at 37 °C (p < 0.05) as compared to larvae raised at 33 °C and 27 °C. In conclusion, we classified the heat waves into three categories: adaptable (33 °C), critical (37 °C), and fatal (42 °C). Prolonged exposure of Culex pallens larvae to extreme heat affects the male reproductive output. These findings may serve as an important reference for forecasting vector and pest dynamics and used to tailor mosquito prevention and control measures.

Dosimetric Comparison and Selection Criteria of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy for Adaptive Re-Plan in T3-4 Nasopharynx Cancer Patients.

BACKGROUND: Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. METHODS: HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. RESULTS: Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. CONCLUSIONS: NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes.

Patterns of decomposition and functional traits for flower and leaf litter in tropical woody species.

The variation within and across species has afterlife effects on carbon and nutrient cycling through the alteration of litter decomposability. However, the focus on leaves may not reflect a whole-plant economic spectrum of strategies. Here, we assessed the patterns and predictors of flower and leaf-litter decomposition at the intra- (i.e., flowers and leaves of the same species) and inter-specific (i.e., flowers and leaves from different species) levels for 29 tropical woody species in northeast Brazil. We evaluated nine functional litter traits, including structural and chemical traits. Flower litter decomposed, on average, three times faster than leaf litter (11.9% and 39.4% mass remaining, respectively) and exhibited higher water-holding capacity (WHC), leaching (LEA), and N, P, and K content. Otherwise, leaf litter showed higher density (DEN) and Ca, Mg, and Na content. The average relative differences in decomposition rate and functional traits between flower and leaf litter did not differ at both intra- and inter-specific levels. The predictors of decomposition were mostly similar, explaining 39% and 37% of flower and leaf litter, respectively. Leaching, P, Ca, Mg, and Na predict both flower and leaf-litter decomposition. However, WHC exclusively predicted flower-litter decomposition, and DEN, N, and K exclusively predicted leaf-litter decomposition. The observed differences in decomposition rate and functional traits between flower and leaf litter indicate that the afterlife effects differ between these plant organs and leverage the role of flower litter and its secondary consequences to nutrient and carbon cycling on ecosystems.

Advances in wearable electronics for monitoring human organs: Bridging external and internal health assessments.

Devices used for diagnosing disease are often large, expensive, and require operation by trained professionals, which can result in delayed diagnosis and missed opportunities for timely treatment. However, wearable devices are being recognized as a new approach to overcoming these difficulties, as they are small, affordable, and easy to use. Recent advancements in wearable technology have made monitoring information possible from the surface of organs like the skin and eyes, enabling accurate diagnosis of the user's internal status. In this review, we categorize the body's organs into external (e.g., eyes, oral cavity, neck, and skin) and internal (e.g., heart, brain, lung, stomach, and bladder) organ systems and introduce recent developments in the materials and designs of wearable electronics, including electrochemical and electrophysiological sensors applied to each organ system. Further, we explore recent innovations in wearable electronics for monitoring of deep internal organs, such as the heart, brain, and nervous system, using ultrasound, electrical impedance tomography, and temporal interference stimulation. The review also addresses the current challenges in wearable technology and explores future directions to enhance the effectiveness and applicability of these devices in medical diagnostics. This paper establishes a framework for correlating the design and functionality of wearable electronics with the physiological characteristics and requirements of various organ systems.

High-Resolution Terahertz Spectroscopy for Medical Diagnostics.

The metabolomics-based approach to diagnostics and therapy monitoring is a fast-emerging trend in modern medicine. Terahertz nonstationary spectroscopy based on the induction and disintegration of freely decaying polarization in the gas mixture during the interaction of radiation with molecules at resonance frequencies is a high-sensitivity method for studying multicomponent gas mixtures, which is promising for identifying metabolites in the thermal decomposition products of biological samples. The paper presents the results of the application of high-resolution terahertz spectroscopy to the study of biological samples taken from patients with certain diseases (pathologically changed tissues of ear-nose-throat organs and similar pathologic tissues formed in other life support systems) to search for characteristic sets of metabolites characterizing the pathology. The world's first measurements of the spectra of pathologic samples of cysts, formed in different life support systems, were carried out, which made it possible to identify similar substances in tissues having the same pathology.

Widely Targeted Metabolomics Analysis of the Roots, Stems, Leaves, Flowers, and Fruits of Camellia luteoflora, a Species with an Extremely Small Population.

Camellia luteoflora is a rare and endangered plant endemic to China. It has high ornamental and potential economic and medicinal value, and is an important germplasm resource of Camellia. To understand the distributions and differences in metabolites from different parts of C. luteoflora, in this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to examine the types and contents of chemical constituents in five organs of C. luteoflora: roots, stems, leaves, flowers, and fruits. The results showed that a total of 815 metabolites were identified in the five organs and were classified into 18 main categories, including terpenoids (17.1%), amino acids (10.4%), flavonoids (10.3%), sugars and alcohols (9.8%), organic acids (9.0%), lipids (7.1%), polyphenols (4.8%), alkaloids (4.8%), etc. A total of 684 differentially expressed metabolites (DEMs) in five organs were obtained and annotated into 217 KEGG metabolic pathways, among which metabolic pathways, ABC transporters, the biosynthesis of cofactors, and the biosynthesis of amino acids were significantly enriched. In DEMs, flowers are rich in flavonoids, polyphenols, organic acids, and steroids; fruits are rich in amino acids, alkaloids, vitamins, and xanthones; stems are rich in lignans; and leaves have the highest relative content of phenylpropanoids, ketoaldehydic acids, quinones, sugars and alcohols, terpenoids, coumarins, lipids, and others; meanwhile, the metabolite content is lower in roots. Among the dominant DEMs, 58 were in roots, including arachidonic acid, lucidone, isoliquiritigenin, etc.; 75 were in flowers, including mannose, shikimic acid, d-gluconic acid, kaempferol, etc.; 45 were in the fruit, including pterostilbene, l-ascorbic acid, riboflavin, etc.; 27 were in the stems, including salicylic acid, d-(-)-quinic acid, mannitol, (-)-catechin gallate, etc.; there was a maximum number of 119 dominant metabolites in the leaves, including oleanolic acid, l-glucose, d-arabitol, eugenol, etc. In sum, the rich chemical composition of C. luteoflora and the significant differences in the relative contents of metabolites in different organs will provide theoretical references for the study of tea, flower tea, edible oil, nutraceuticals, and the medicinal components of C. luteoflora.

Organ-on-chip technology: Opportunities and challenges.

Organ-on-chip (OOC) technology is an innovative approach that reproduces human organ structures and functions on microfluidic platforms, offering detailed insights into intricate physiological processes. This technology provides unique advantages over conventional in vitro and in vivo models and thus has the potential to become the new standard for biomedical research and drug screening. In this mini-review, we compare OOCs with conventional models, highlighting their differences, and present several applications of OOCs in biomedical research. Additionally, we highlight advancements in OOC technology, particularly in developing multiorgan systems, and discuss the challenges and future directions of this field.

Development of a robotic-assisted handling and manipulation system for the high-scale bioproduction of 3D-bioprinted organ-on-a-chip devices.

Organs-on-a-chip (OoCs) have proven to mimic the basic physiological behavior of organs and the influence of therapeutics on them in greater detail than conventional models, resulting in enormous projected market growth rates. However, the breakthrough to profitable commercialization of that technology has not yet been achieved, partly because the production process chain is characterized by a high proportion of manual laboratory work. The present work addresses this point. Utilizing affordable components, a demonstrator was developed that can be integrated into an existing 3D-bioprinting system and enables the automated production of perfusion-ready OoC devices starting from pre-fabricated injection-molded microfluidic chips. To this end, a corresponding process chain was first defined, and an expandable, configurable algorithm was developed and validated in the form of a finite state machine (FSM). This algorithm controls a modified 4-axis robot arm that covers the steps upstream and downstream of the printing process in the manufacturing process and achieves success rates of up to 100 %. A virtual interface between the robot and printer enables mutual communication and full integration of the algorithm into the process chain. Steps that pose a challenge for the automation of the process chain and appropriate countermeasures and optimizations were identified. This lays the foundation for scaling and standardizing the automated production of OoCs.

Long-term biological effects after acute 131I-administration of two rat models (with and without thyroid).

PURPOSE: Radioiodine-131 (RAI or iodine-131) is one of the most frequently used radionuclides for diagnosis and therapy of thyroid diseases (90% of all therapies in nuclear medicine). In order to optimize the patient protection, it is important to evaluate the long-term biological effects of RAI therapy on non-target organs. MATERIALS AND METHODS: An experimental animal model has been adopted, it consists on miming RAI therapy. An activity of RAI has been administrated in two models of Wistar rats: the first model with an intact thyroid gland (Thy + model), and the second one was thyroidectomized (Thy- model). For each model, 6 rats were orally contaminated with a solution 18.5 ± 1MBq of [131I]NaI and 6 others rats were used as controls. The 24 rats have been placed in individual cages for a period of 08 months then they were euthanized. The blood was collected by cardiac puncture and all organs were immediately removed. A fraction of thyroid, liver, kidneys and testicles was put in vials containing formaldehyde (10%) for histological investigation. RESULTS: Histological observations show some liver disorders more accentuated in the case of the Thy- model, the appearance of kidney tissue effects (hemosiderin deposits, fibrosis and glomerular necrosis) for both models and an absence of any anomaly for the testicles slides. The disturbance of blood parameters specific to each organ has been revealed. CONCLUSIONS: Long-term biological effect of 131I-administration shows the appearance of various histological disorders confirmed by disturbances in hepatic and renal functions.

Evaluation of the systemic effect of bone formation marker released by endodontic calcium silicate-based sealers in local tissues, the bloodstream, and body organs.

Calcium silicate-based sealers are bioactive materials that release ions when in contact with body fluids. Therefore, this study aims mapping/trace bone formation markers released by MTA Fillapex, BioRoot RCS, and experimental tricalcium silicate-based sealer (CEO) into subcutaneous tissues, bloodstream and body organs. Toward, polyethylene tubes filled with sealers were implanted into connective tissue of Wistar rats. On days 7, 15, 30, and 45 after implantation, blood samples were collected to measure calcium (Ca2+), phosphorus (P), and alkaline phosphatase (ALP) levels. Thereafter, the animals were killed, and the brain, liver, kidneys, and subcutaneous tissue were removed and processed to determine the concentrations of Ca2+ and P by ICP-OES. Similar Ca2+ levels were observed in subcutaneous tissue for all groups, although, at 45 days, it was identified a reduction in Ca2+ serum levels of CEO compared to those two other sealers and an increase in Ca2+ levels in the liver compared to those released by MTA Fillapex. In contrast, no trace of P was detected in any tissue; moreover, plasma P and ALP serum levels of MTA Fillapex were higher at day 30. Our findings showed that Ca2+ were identified in local tissues, bloodstream, and organs from all sealers. The up-regulation of bone marker levels promoted by sealers can modify body homeostasis and induce tissue damage. Besides, MTA Fillapex was associated with a raise of bone marker levels, suggesting a possible systemic effect. The sealer composition can affect not only the local repair process but also the systemic health.

Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.

Somatic activating mutations in PIK3CA are common drivers of vascular and lymphatic malformations. Despite common biophysical signatures of tissues susceptible to lesion formation, including compliant extracellular matrix and low rates of perfusion, lesions vary in clinical presentation from localized cystic dilatation to diffuse and infiltrative vascular dysplasia. The mechanisms driving the differences in disease severity and variability in clinical presentation and the role of the biophysical microenvironment in potentiating progression are poorly understood. Here, we investigate the role of hemodynamic forces and the biophysical microenvironment in the pathophysiology of vascular malformations, and we identify hemodynamic shear stress and defective endothelial cell mechanotransduction as key regulators of lesion progression. We found that constitutive PI3K activation impaired flow-mediated endothelial cell alignment and barrier function. We show that defective shear stress sensing in PIK3CA E542K endothelial cells is associated with reduced myosin light chain phosphorylation, junctional instability, and defective recruitment of vinculin to cell-cell junctions. Using 3D microfluidic models of the vasculature, we demonstrate that PIK3CA E542K microvessels apply reduced traction forces and are unaffected by flow interruption. We further found that draining transmural flow resulted in increased sprouting and invasion responses in PIK3CA E542K microvessels. Mechanistically, constitutive PI3K activation decreased cellular and nuclear elasticity resulting in defective cellular tensional homeostasis in endothelial cells which may underlie vascular dilation, tissue hyperplasia, and hypersprouting in PIK3CA-driven venous and lymphatic malformations. Together, these results suggest that defective nuclear mechanics, impaired cellular mechanotransduction, and maladaptive hemodynamic responses contribute to the development and progression of PIK3CA-driven vascular malformations.

Allocation of nitrogen and phosphorus in the leaves, stems, and roots of Artemisia: a case study in phylogenetic control.

Introduction: The allocation of nitrogen (N) and phosphorus (P) among plant organs is an important strategy affecting growth and development as well as ecological processes in terrestrial ecosystems. However, due to lack of systematic investigation data, the allocation strategies of N and P in the three primary plant organs (e.g., leaves, stems and roots) are still unclear. Methods: A total of 912 individuals of 62 Artemisia species were examined across a broad environmental expanse in China, and the N and P concentrations of leaves, stems and roots were measured to explore the allocation strategies in different subgenera, ecosystem types, and local sites. Results and discussion: Across all 62 species, the N vs. P scaling exponents for leaves, stems and roots were 0.67, 0.59 and 0.67, respectively. However, these numerical values differed among subgenera, ecosystem types, and local sites. Overall, the numerical values of N vs. P scaling exponents comply with a 2/3-power function for each Artemisia organ-type reflecting a phylogenetically conserved allocation strategy that has nevertheless diversified with respect to local environmental conditions. These results inform our understanding of N and P stoichiometric patterns and responses to abiotic factors in an ecologically broadly distributed angiosperm genus.

Hippo effector, Yorkie, is a tumor suppressor in select Drosophila squamous epithelia.

Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that the YAP/TAZ/Yki signaling drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed organ growth, if any, remains elusive. Out-of-context gain of YAP/TAZ/Yki signaling often turns oncogenic. Paradoxically, mechanically strained, and differentiated squamous epithelia display developmentally programmed constitutive nuclear YAP/TAZ/Yki signaling. The unknown, therefore, is how a growth-promoting YAP/TAZ/Yki signaling restricts proliferation in differentiated squamous epithelia. Here, we show that reminiscent of a tumor suppressor, Yki negatively regulates the cell growth-promoting PI3K/Akt/TOR signaling in the squamous epithelia of Drosophila tubular organs. Thus, downregulation of Yki signaling in the squamous epithelium of the adult male accessory gland (MAG) up-regulates PI3K/Akt/TOR signaling, inducing cell hypertrophy, exit from their cell cycle arrest, and, finally, culminating in squamous cell carcinoma (SCC). Thus, blocking PI3K/Akt/TOR signaling arrests Yki loss-induced MAG-SCC. Further, MAG-SCCs, like other lethal carcinomas, secrete a cachectin, Impl2-the Drosophila homolog of mammalian IGFBP7-inducing cachexia and shortening the lifespan of adult males. Moreover, in the squamous epithelium of other tubular organs, like the dorsal trunk of larval tracheal airways or adult Malpighian tubules, downregulation of Yki signaling triggers PI3K/Akt/TOR-induced cell hypertrophy. Our results reveal that Yki signaling plays an instructive, antiproliferative role in the squamous epithelia of tubular organs.

Evaluation of structural features of anabolic-androgenic steroids: entanglement for organ-specific toxicity.

Anabolic-androgenic steroids (AASs), more correctly termed "steroidal androgens", are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences, highlighting the need for improved understanding and prevention strategies. AASs are not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.