Initial Stage Research Articles

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet.

Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

Testing analytical methods to derive the cosmic-ray ionisation rate in cold regions via synthetic observations

Context. Cosmic rays (CRs) heavily impact the chemistry and physics of cold and dense star-forming regions. However, the characterisation of their ionisation rate continues to pose a challenge from the observational point of view. Aims. In the past, a few analytical formulas have been proposed to infer the cosmic-ray ionisation rate, ζ2, from molecular line observations. These have been derived from the chemical kinetics of the involved species, but they have not yet been validated using synthetic data processed with a standard observative pipeline. In this work, we aim to bridge this gap. Methods. We performed a radiative transfer on a set of three-dimensional magneto-hydrodynamical simulations of prestellar cores, exploring different initial ζ2, evolutionary stages, types of radiative transfer (for instance assuming local-thermodynamic-equilibrium conditions), and telescope responses. We then computed the column densities of the involved tracers to determine ζ2, employing a recently proposed method based on the detection of H2D+. We compared this approach with a previous method, based on more common tracers. Both approaches are commonly used. Results. Our results confirm that the equation based on the detection of H2D+ accurately retrieves the actual ζ2 within a factor of two to three in the physical conditions explored in our tests. Since we have also explored a non-local thermodynamic equilibrium (non-LTE) radiative transfer, this work indirectly offers insights into the excitation temperatures of common transitions at moderate volume densities (n ≈ 105 cm−3). We also performed a few tests using a previous methodology that is independent of H2D+, which overestimates the actual ζ2 by at least two orders of magnitude. We considered a new derivation of this method, however, we found that it still leads to high over-estimations. Conclusions. The method based on H2D+ is further validated in this work and demonstrates a reliable method for estimating ζ2 in cold and dense gas. On the contrary, the former analytical equation, as already pointed out by its authors, has no global domain of application. Thus, we find that it ought to be employed with caution.

Rancang Bangun Game Edukasi Pengenalan Pahlawan Berbasis Android

Learning media has a crucial role for teachers in conveying information during learning activities. However, many elementary schools currently still rely on audio-visual media and teaching aids, which can cause boredom among students during the teaching and learning process. Indonesian heroes are those who fought for Indonesian independence against the colonialists. Therefore, strategies are needed that can awaken feelings of love for the country and patriotism in children. It is hoped that the use of Android-based games as a learning medium can increase students' interest in learning, especially in understanding national heroes. The design of this multimedia application follows the Game Development Life Cycle (GDLC) method with initialization, preproduction, production, testing, beta and release stages. By designing this educational game, the author hopes to help students at SD Negeri 1 Karangsentul to get to know and remember Indonesia's national hero figures, as well as increase their sense of nationalism.

Early-Life Lead Exposure: Risks and Neurotoxic Consequences.

Lead (Pb) does not have any biological function in a human, and it is likely no safe level of Pb in the human body. The Pb exposure impacts are a global concern for their potential neurotoxic consequences. Despite decreasing both the environmental Pb levels and the average blood Pb levels in the survey populations, the lifetime redistribution from the tissues-stored Pb still poses neurotoxic risks from the low-level exposure in later life. The growing fetus and children hold their innate high-susceptible to these Pb-induced neurodevelopmental and neurobehavioral effects. This article aims to evaluate cumulative studies and insights on the topic of Pb neurotoxicology while assessing the emerging trends in the field. The Pb-induced neurochemical and neuro-immunological mechanisms are likely responsible for the high-level Pb exposure with the neurodevelopmental and neurobehavioral impacts at the initial stages. Early-life Pb exposure can still produce neurodegenerative consequences in later life due to the altered epigenetic imprints and the ongoing endogenous Pb exposure. Several mechanisms contribute to the Pb-induced neurotoxic impacts, including the direct neurochemical effects, the induction of oxidative stress and inflammation through immunologic activations, and epigenetic alterations. Furthermore, the individual nutritional status, such as macro-, micro-, or antioxidant nutrients, can significantly influence the neurotoxic impacts even at low-level exposure to Pb. The prevention of early-life Pb exposure is, therefore, the critical determinant for alleviating various Pb-induced neurotoxic impacts across the different age groups.

Predicting and detecting fires on multispectral images using machine learning methods

In today's world, fire forecasting and early detection play a critical role in preventing disasters and minimizing damage to the environment and human settlements. The main goal of the study is the development and testing of machine learning algorithms for automated detection of the initial stages of fires based on the analysis of multispectral images. Within the framework of this study, the capabilities of three popular machine learning methods: extreme gradient boosting, logistic regression, and vanilla convolutional neural network (vanilla CNN), are considered in the task of processing and interpreting multispectral images to predict and detect fires. XGBoost, as a gradient-boosted decision tree algorithm, provides high processing speed and accuracy, logistic regression stands out for its simplicity and interpretability, while vanilla CNN uses the power of deep learning to analyze spatial and spectral data. The results of the study show that the integration of these methods into monitoring systems can significantly improve the efficiency of early fire detection, as well as help in predicting potential fires.

Comparative Analysis of Polycystic Ovary Syndrome Detection Using Machine Learning Algorithms

INTRODUCTION: Polycystic Ovary Syndrome is a condition in which the ovaries manufacture androgen, seen in small traces, resulting in the production of cysts. Menstrual cycle abnormalities, clinical and/or biochemical hyperandrogenism, and the presence of polycystic ovaries on ultrasound should all be used to diagnose PCOS. PCOS appears to be a multifaceted illness influenced by both genetic and environmental factors and the symptoms include excessive hair on the face and body, weight gain, voice changes, skin type changes, and irregular periods.
 OBJECTIVES: This is the objective of this paper is to identify PCOS in its initial stage.
 METHODS: To address this issue the study proposes a comparison of various machine learning algorithms and optimization techniques Among which GSCV gave the best result of 94% accuracy, followed by TPOT with 91% accuracy. Additionally, we also applied Feature selection methods to eliminate zero-importance features to increase the accuracy of algorithms.
 RESULTS: The main results obtained in this paper This study explored various Feature selection techniques, ML and DL models. It is shown that Grid Search CV and TPOT classifier were best classifiers with 94% and 91% respectively.
 CONCLUSION: These are the conclusions of this paper and this study will explore various DL methodologies and try to find out best optimal results for the PCOS Detection. And also, to develop an PCOS detection application to keep track of menstrual cycles and track activities and symptoms for PCOS.

An ADMM-enabled robust optimization framework for self-healing scheduling of smart grids integrated with smart prosumers

Enhancing the reliability of energy networks and minimizing downtime is crucial, making self-healing smart grids indispensable for ensuring a continuous power supply and fortifying resilience. As smart grids increasingly incorporate decentralized prosumers, innovative coordination strategies are essential to fully exploit their potential and improve system self-healing capabilities. To address this need, this paper presents a novel bi-level strategy for managing the self-healing process within a smart grid influenced by Hydrogen Refueling Stations (HRSs), Electric Vehicle Charging Stations (EVCSs), and energy hubs. This approach taps into the combined potential of these prosumers to boost system self-healing speed and reliability. In the initial stage, the Smart Grid Operator (SGO) conducts self-healing planning during emergencies, communicating required nodal capacities to prevent forced load shedding and outlining incentives for smart prosumers. Subsequently, prosumers schedule their activities and contribute flexible capacities to the SGO. Bridging the first and second stages, an adaptive Alternating Direction Method of Multipliers (ADMM) algorithm ensures convergence between the SGO and prosumer schedules within a decentralized framework. This strategy underwent implementation on a 118-node distribution system using GAMS. Results demonstrate that the proposed concept reduces Forced Load Shedding (FLS) by 32.04% and self-healing costs by 17.48% through effective utilization of smart prosumers' flexible capacities. Furthermore, outcomes indicate that the SGO reduces FLS by 6.69% by deploying Mobile Electrical Energy Storages (MEESs) and Mobile Fuel Cell Trucks (MFCTs) to critical nodes.

Enhancing Lung Nodule Classification: A Novel CViEBi-CBGWO Approach with Integrated Image Preprocessing.

Cancer detection and accurate classification pose significant challenges for medical professionals, as it is described as a lethal illness. Diagnosing the malignant lung nodules in its initial stage significantly enhances the recovery and survival rates. Therefore, a novel model named convolutional vision Elman bidirectional-based crossover boosted grey wolf optimization (CViEBi-CBGWO) has been proposed to enhance classification accuracy. CT images selected for further preprocessing are obtained from the LUNA16 dataset and LIDC-IDRI dataset. The data undergoes preprocessing phases involving normalization, data augmentation, and filtering to improve the generalization ability as well as image quality. The local features within the preprocessed images are extracted by implementing the convolutional neural network (CNN). For extracting the global features within the preprocessed images, the vision transformer (ViT) model consists of five encoder blocks. The attained local and global features are combined to generate the feature map. The Elman bidirectional long short-term memory (EBiLSTM) model is applied to categorize the generated feature map as benign and malignant. The crossover operation is integrated with the grey wolf optimization (GWO) algorithm, and the combined form of CBGWO fine-tunes the parameters of the CViEBi model, eliminating the problem of local optima. Experimental validation is conducted using various evaluation measures to assess effectiveness. Comparative analysis demonstrates a superior classification accuracy of 98.72% in the proposed method compared to existing methods.

CO Cofeeding Affects Product Distribution in CH3Cl Coupling over ZSM-5 Zeolite: Pressure Twists the Plot.

C1 coupling reactions over zeolite catalysts are central to sustainable chemical production strategies. However, questions persist regarding the involvement of CO in ketene formation, and the impact of this elusive oxygenate intermediate on reactivity patterns. Using operando photoelectron photoion coincidence spectroscopy (PEPICO), we investigate the role of CO in methyl chloride conversion to hydrocarbons (MCTH), a prospective process for methane valorization with a reaction network akin to methanol to hydrocarbons (MTH) but without oxygenate intermediates. Our findings reveal the transformative role of CO in MCTH at the low pressures, inducing ketene formation in MCTH and boosting olefin production, confirming the Koch carbonylation step in the initial stages of C1 coupling. We uncover pressure-dependent product distributions driven by CO-induced ketene formation, and its subsequent desorption from the zeolite surface, which is enhanced at low pressure. Inspired by the above results, extension of the co-feeding approach to CH3OH as another simple oxygenate showcases the additional potential for improved catalyst stability in MCTH at ambient pressure.

High-temperature tensile strength of C/SiC composite under laser-induced high heating flux in an aerobic environment

Based on the advantages of laser high brightness, a high-temperature mechanical property measuring device has been developed, which can measure the high-temperature strength of C/SiC composites under the condition of short-term high-temperature rise rate and solve the problem of over-oxidation of materials in conventional high-temperature mechanical properties experiments. The experimental results show that the maximum temperature rise rate is 260 ℃/s at the initial heating stage, and the test time is controlled within 35 s. The tensile strength of the prepared C/SiC composites decreased first and then increased at high temperatures and laser-induced high temperatures. The experimental results are similar to those in the literature under the inert atmosphere. Oxidation has less of an effect on the mechanical characteristics of materials under conditions of rapid temperature rise. The system can be used to test the mechanical properties of composite materials at high temperatures and as a simulation platform for the thermal response of specific thermal protection systems subjected to a constant heat flux. This study can provide a new idea for testing ultra-high temperature mechanical properties of C/SiC materials and provide key technical support for the engineering application and high-temperature testing of C/SiC materials in high-temperature environments.

Analysis of intervarietal soybean hybrids at the initial breeding stages

The results of the study of recombinant soybean hybrids in terms of the degree of heterosis effect, phenotypic dominance and transgressive variability in economically valuable traits with the subsequent selection of the most promising hybrid combinations are presented. The study was conducted from 2018 to 2022 in the laboratory of soybean breeding in the conditions of the steppe zone of the Primorsky Territory. Of the ten hybrid combinations obtained, the maximum effect of heterosis in the first generation was observed in the combinations Primorskaya 1385 × Kofu, Primorskaya 1385 × Dong nong 690, Hei He 38 × Taifun. Phenotypic overdominance of inheritance of indicators (from 1.6 to 76.7) was recorded in all hybrids. Transgressive variability of intervarietal soybean hybrids in the second and third generations varied by combination and generation. High values of the degree of transgression in the third generation were observed in the combinations Primorskaya 1385 × Kofu and Hei He 38 × Talppod-Fisk, in terms of the number of seeds per plant – Primorskaya 1385 × Taifun and Kofu × Taifun, in terms of seed weight per plant – Dong nong 690 × Taifun and Hei He 38 × Taifun. A decrease in the frequency of transgression of hybrids by the third generation was found. The highest values of the degree and frequency of transgression in plant height were observed in the hybrid combinations Hei He 38 × Taifun and Hei He 38 × Talppod-Fisk. Based on the results of the study of the promising soybean genotypes, recombinant hybrids with high productivity and 1000-seed weight in the combinations Kyoto × Dong nong 690 and Monsoon × Taifun were isolated. The hybrids tested had different ripeness groups. Not always the manifestation of high effect of heterosis and transgressive variability in the first – third generations serves as a guarantee of further obtaining samples with high economically valuable indicators.

Radioatelier: Czech radio space for acoustic art 2003–2022

In 2003, a new radio programme called Radioatelier was launched as part of the Czech Radio 3 – Vltava broadcast, the national public service art channel. It was aimed at presenting experimental radio forms, something completely unprecedented at that time. With 213 new commissions by December 2022, the programme entered its third decade of existence, having won a number of major radio art awards, while facing threats of impending programme cancellation in 2023. The present article is quite personal, offering generational insights of the producer, who was privileged enough to set goals and scope of the programme in its initial stages and who went on to co-exist with it for the following two decades. It also presents the complete list of sound compositions commissioned by Radioatelier between 2003 and 2022.

Psychometric Validation of the Persian Version of Multidimensional Health Locus of Control Scale (MHLC-C) for Menopausal Women

Background. The Health Locus of Control (HLC) serves as a mediator between an individual’s behaviors and health status, influenced by various cultural, environmental, and situational factors. Its measurement reflects health beliefs and attitudes, ultimately leading to healthy behaviors. Menopause is a significant phenomenon in women’s lives, often resulting in a wide range of symptoms and health issues. Therefore, the perception of HLC plays a crucial role in promoting healthy behaviors and managing menopausal symptoms. This study aimed to assess the validity and reliability of the Persian version of the short form Multidimensional Health Locus of Control Scale (MHLC) in Iranian menopausal women and explore its interrelationships. Methods. A cross-sectional study was conducted with 271 menopausal women from September to November 2023. Psychometric properties such as construct validity (confirmed through confirmatory factor analysis), convergent validity (evaluated using average variance extracted), and internal consistency (assessed by Cronbach’s alpha, composite reliability and rho_A factor) were examined. Discriminant validity was determined using the Fornell–Larcker criterion. Reliability was further established through Cronbach’s alpha and McDonald’s Omega coefficients. The predictive relevance of the model and associations between constructs were analyzed using various statistical measures. Data analysis was conducted using SPSS v.27 and Smart PLS 3.0 software. Limitations of this study include that it was conducted in urban health centers, only women with at least primary education were included, and reliance on self-reported data. Results. The initial stage of construct validity involved the Kolmogorov–Smirnov test, with confirmatory factor analysis demonstrating a good model fit. Significant correlations were found between internal health control and factors related to doctors and other people, indicating that internal health control directly influences these factors in managing menopausal symptoms and health problems. Cronbach’s alpha and McDonald’s Omega coefficients for the 13-item MHLC-C scale were satisfactory (0.81 and 0.72, respectively). Conclusions. The Persian version of the 13-item MHLC-C has been validated as a reliable tool for assessing the health locus of control in Iranian menopausal women. Internal health control was found to significantly impact perceptions related to doctors and other people, highlighting its importance in managing menopausal symptoms effectively.

Mechanism of NCNTs Growth on Foamed Nickel and Thus-Prepared PS Hydrogenation High-Performance Carrier NCNTs@FN.

Traditional heterogeneous catalysts are affected in the catalytic hydrogenation of PS by the scale effect, viscosity effect, adhesion effect, and conformational effect, resulting in poor activity and stability. Monolithic Pd-CNTs@FN catalysts could eliminate or weaken the impact of these negative effects. We grew nitrogen-doped carbon nanotubes (NCNTs) on monolithic-foamed nickel (FN) and investigate their growth mechanism. Meanwhile, the feasibility of using the NCNTs@FN carrier for PS hydrogenation reaction was also verified. The growth of NCNTs on FN can be divided into 3 stages: initial growth stage, stable growth stage, and supersaturation stage. Finally, a three-layer structure of NCNT layer, dense carbon layer, and FN skeleton is formed. Two types of structures, nickel-doped carbon nanotubes (NiCNTs) and C-Ni alloy, are formed by combining C and Ni, while four nitrogen-doped structures, NPD, NPR, NG, and NO, are formed by C and N. The prepared carrier exhibited an extremely outstanding specific surface area (2.829 × 106 cm2/g) and strength (no NCNTs falling off after 24 h 500 rpm agitation), as well as high catalytic activity for PS hydrogenation after loaded with Pd (2.13 ± 0.95 nm), with a TOF of up to 27.6 gPS/(gPd•h). After 8 repetitions of the catalyst, there was no significant decrease in activity. This proves the excellent performance of Pd-NCNTs@FN in polymer hydrogenation reactions, laying a solid foundation for further research on the mechanism of NCNTs promoting PS hydrogenation and regulating the growth of NCNTs.

Effects of 60Co γ-irradiation treatment on the diversity of fungal microflora in blueberries during cold storage

In the present study, the effects of 60Co-γ irradiation on the diversity of fungal microflora in blueberries during cold storage have been explored in detail. The effects of irradiation on the fungal microflora in blueberries could be observed at the lowest effective dose of 1.0 kGy. The genome library of fungal microflora in blueberries was evaluated by tusing Shannon, Simpson, Chao1, and ACE indices, presenting good coverage of blueberry samples. Principal coordinate analysis clarified the differences in the evolution and clustering of fungi in blueberries under different irradiation levels. The composition and diversity of fungal microflora in blueberries treated with different doses of radiation exhibited significant differences under cold storage of 4°C. However, most of the fungi belonged to the Ascomycota at the phylum. The fungal microflora was relatively stable at the initial stage of cold storage, however, the diversity of fungal species in irradiated blueberries varied greatly in the middle stage around the 15th day. This comprehensive study provides deeper insight about the effects of irradiation on the evolution of fungal microflora in blueberries during cold storage. The findings of this study lay a good foundation for post-harvest storage and preservation of blueberries.

Deriving learning outcomes for an applied health technology course for PhD students

This study discusses the initial stage of development of a PhD course within the Applied Health Technology (AHT) area, in a multi-professional and transdisciplinary environment. The research aimed to align stakeholders' and PhD graduates' perspectives to create learning outcomes for a proposed AHT course. Semi-structured interviews were conducted with stakeholders and graduates of the program, and the results were analysed using a qualitative content analysis method. The identified themes related to AHT perspectives, issues with working with AHT projects, program goals and course goals. These guided the creation of four strategically aligned learning outcomes for the proposed course.

The Role of [18F]FDG PET/CT in the Characterization of Thymic Epithelial Tumors at Initial Stage.

Purpose: The aim of this study was to evaluate the potential role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUVmax, MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUVmax, TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUVmax, MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. NCT04539964; August 31, 2020.

Repulsive Lateral Interaction of Water Molecules at the Initial Stages of Adsorption in Microporous AlPO4-11 According to 27Al NMR and DFT.

Lateral (adsorbate-adsorbate) interactions between adsorbed molecules affect various physical and chemical properties of microporous adsorbents and catalysts, influencing their functional properties. In this work, we studied the hydration of microporous AlPO4-11 aluminophosphate, which has an unusually ordered structure upon adsorption of water vapor, and according to 27Al NMR data, only tetrahedrally or octahedrally coordinated Al sites are present in the AlPO4-11. These 27Al NMR data are consistent with the results of density functional theory (DFT) calculations of hydrated AlPO4-11, which revealed the presence of a strong repulsive lateral interaction at the initial stage of adsorption, suppressing the adsorption of water on neighboring (separated by one -O-P-O- bridge) Al crystallographic sites. As a result, of all the different aluminum sites, only half of the Al1 sites adsorb two water molecules and acquire octahedral coordination.

A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids.

To investigate the impact of rapamycin on the differentiation of hair cells. Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages. Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2+ progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects. Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2+ progenitors in an in vitro setting.