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Thyroid hormones are produced by the thyroid gland and are essential for regulating metabolism, growth and development. Maintenance of circulating thyroid hormone levels within an appropriate range is thus a prerequisite for health. In vivo, this objective is, at least in part, facilitated through an extracellular storage depot of thyroglobulin, the glycoprotein precursor for thyroid hormones, in the thyroid follicular lumen. The molecular basis for how soluble thyroglobulin molecules form such dense depot assemblies remains elusive. Here, we describe in vitro biophysical analysis of thyroglobulin phase behaviour, suggesting that thyroglobulin is prone to undergoing ionic strength-dependent phase separation, leading to the formation of liquid-like condensates. Fluorescence photobleaching measurements further show that these condensates age as a function of time to form reversible gel-like high density storage depots of thyroglobulin. IF experiments on mouse and human thyroid follicles ex vivo reveal that spherical globules of Tg protein dense phase are present in the follicular lumen, consistent with the idea that Tg undergoes phase separation. These findings reveal a molecular mechanism for the last-come-first-served process of thyroglobulin storage and release, suggesting a role for extracellular phase separation in thyroid hormone homeostasis by providing organizational and architectural specificity without requiring membrane-mediated confinement. A biophysical study on phase separation behaviour of thyroglobulin (Tg) in vitro, combined with ex vivo immunofluorescence experiments, suggests that extracellular phase separation mediates storage and release of Tg in the thyroid follicular lumen.

Thyroid hormones are produced by the thyroid gland and are essential for regulating metabolism, growth and development. Maintenance of circulating thyroid hormone levels within an appropriate range is thus a prerequisite for health. In vivo, this objective is, at least in part, facilitated through an extracellular storage depot of thyroglobulin, the glycoprotein precursor for thyroid hormones, in the thyroid follicular lumen. The molecular basis for how soluble thyroglobulin molecules form such dense depot assemblies remains elusive. Here, we describe in vitro biophysical analysis of thyroglobulin phase behaviour, suggesting that thyroglobulin is prone to undergoing ionic strength-dependent phase separation, leading to the formation of liquid-like condensates. Fluorescence photobleaching measurements further show that these condensates age as a function of time to form reversible gel-like high density storage depots of thyroglobulin. Immunofluorescence experiments on mouse and human thyroid follicles ex vivo reveal that spherical globules of Tg protein dense phase are present in the follicular lumen, consistent with the idea that Tg undergoes phase separation. These findings reveal a molecular mechanism for the last-come-first-served process of thyroglobulin storage and release, suggesting a role for extracellular phase separation in thyroid hormone homeostasis by providing organizational and architectural specificity without requiring membrane-mediated confinement.

Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, l-aspartic acid, l-ornithine, Ethanolamine, l-Serine, l-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.

Background The triglyceride-glucose (TyG) index and related parameters, as well as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), have been developed as insulin resistance markers to identify individuals at risk for non-alcoholic fatty liver disease (NAFLD). However, its use for predicting NAFLD in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this study, we aimed to observe the performance of insulin resistance indices in diagnosing NAFLD combined with T2DM and to compare their diagnostic values in clinical practice. Patients and methods Overall, 268 patients with T2DM from the Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine were enrolled in this study and divided into two groups: an NAFLD group (T2DM with NAFLD) and a T2DM group (T2DM without NAFLD). General information and blood indicators of the participants were collected, and insulin resistance indices were calculated based on these data. Receiver operating characteristic (ROC) analysis was conducted to calculate the area under the curve (AUC) for insulin resistance-related indices, aiming to assess their ability to discriminate between T2DM patients with and without NAFLD. Results ROC analysis revealed that among the five insulin resistance-related indices, four parameters (TyG, TyG-body mass index [BMI], TyG-waist circumference [WC], and TyG- (waist–hip ratio [WHR]) exhibited high predictive performance for identifying NAFLD, except for HOMA-IR (AUCs:0.710,0.738,0.737 and 0.730, respectivly). TyG-BMI demonstrated superior predictive value, especially in males. For males, the AUC for TyG-BMI was 0.764 (95% confidence interval [CI] 0.691–0.827). The sensitivity and specificity for male NAFLD were 90.32% and 47.89%, respectively. Moreover, in the Generalized linear regression models, there were positive associations of TyG, TyG-BMI, TyG-WC, TyG-WHR, and HOMA-IR with controlled attenuation parameter (CAP), with β values of 21.30, 0.745, 0.247, and 2.549 (all P  < 0.001), respectively. Conclusion TyG-BMI is a promising predictor of NAFLD combined with T2DM, particularly in lean male patients.

Background The aim of this study was to identify the clinical factors associated with serum trough concentrations of vancomycin crystalline degradation product (CDP-1) and to determine the impact of CDP-1 on chemiluminescence microparticle immunoassay (CMIA) results among patients with chronic kidney disease (CKD). Methods In this retrospective observational study, patients with CKD who were receiving vancomycin intravenously were included if steady-state serum trough levels of vancomycin were available. Patients were allocated to three groups on the basis of their estimated creatinine clearance (eCrCl) on the day of trough level monitoring: G1 (60 < eCrCl ≤ 90 mL/min), G2 (30 < eCrCl ≤ 60 mL/min), and G3 (eCrCl ≤ 30 mL/min). CDP-1 serum concentrations were determined via ultra-high performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS/MS). Vancomycin serum concentrations measured via CMIA were compared with those measured via UPLC‒MS/MS. Multiple linear regression analyses were performed to identify factors associated with the CDP-1 concentration and the ratio of vancomycin concentration determined via CMIA to vancomycin concentration via UPLC‒MS/MS (V CMIA /V UPLC-MS/MS ). Results Among the 167 patients included, 49 (29.34%), 69 (41.32%), and 49 (29.34%) were allocated to G1, G2, and G3, respectively. There were significant differences in the CDP-1 trough concentrations and V CMIA/ V UPLC-MS/MS ratios between the three groups. In the multivariate analysis, eCrCl levels (P < 0.001), the time interval from the initial dose to the trough level (P < 0.001), and vancomycin dose (P < 0.001) were associated with CDP-1 trough concentrations. The CDP-1 trough concentration was positively associated with the V CMIA /V UPLC-MS/MS ratio (P = 0.002). Conclusions Delayed timing of trough level sampling could contribute to increased CDP-1 levels and the overestimation of vancomycin levels, especially in patients with severe deterioration in renal function. It may be necessary to increase the frequency of TDM and select quantitative methods to measure vancomycin serum levels without interfering with CDP-1.

Medulloblastoma is a malignancy of the central nervous system that occurs most frequently in childhood and is often difficult to diagnose due to its similarities to conventional imaging findings for other pediatric intracranial tumors such as astrocytomas and ependymomas. The purpose of this study was to identify new metabolites and differential metabolic pathways by analyzing the significantly different metabolites present in the plasma of children with medulloblastoma in comparison with those with other intracranial tumors. Plasma was collected from 37 children with medulloblastoma and 34 children with other intracranial tumors. Targeted and non-targeted metabolomics based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analyses were performed to determine metabolic changes in pediatric medulloblastomas versus other intracranial tumors. Based on multivariate statistical analysis and regression models, we identified differential metabolites in the plasma and investigated different metabolic pathways. A total of 61 differential metabolites in the plasma of children with medulloblastoma were identified by non-targeted metabolomics analysis. In addition, targeted metabolomics analysis identified four differential amino acids, thus allowing us to establish a diagnostic model for children with medulloblastoma. Metabolic pathway analysis showed that there were significant differences in patients with medulloblastoma in terms of glycerophospholipid and α-linolenic acid metabolism pathways as well as several amino acid metabolism pathways (phenylalanine, tyrosine, and tryptophan biosynthesis). We identified differential profiles of key plasma metabolites between children with medulloblastoma and other forms of intracranial tumor, thus providing a basis for identifying early diagnostic markers of medulloblastoma and new therapeutic targets and strategies. Graphical Abstract

Transparent metafilms with spectrally selective properties have shown great potential in energy-efficient window systems. Most previous studies focused on optimizing materials and thicknesses to enhance visible transmittance and near-infrared (NIR) reflectance. However, few have considered how the position of the metafilms on the glass affects overall optical and thermal performance, especially in the mid-infrared (MIR) range critical for radiative cooling. In this work, we propose and analyze a five-layer TiO /Ag/TiO /Ag/TiO structure and systematically evaluate its performance under two typical installation scenarios. Numerical simulations based on the transfer matrix method show that both configurations maintain a high visible transmittance (∼0.88) and an effective NIR reflectance (∼0.98). Notably, a substantial difference is observed within the atmospheric transparency window 8–14 μm, where the interior-coated configuration possesses a high emissivity of 0.8. This value significantly exceeds the average emissivity of 0.01 found for the exterior-coated configuration, thereby resulting in superior passive radiative cooling capability. Moreover, we also compared the net radiative cooling power under the two configurations. These findings reveal that the position of the transparent metafilms critically influences MIR radiation. Coating placement on the interior surface not only maintains favorable solar modulation but also markedly enhances the thermal dissipation. This study offers theoretical guidance and practical insight into the design and implementation of metafilms in energy saving window systems aimed at reducing energy consumption, especially in regions with hot climates.

Silicon dioxide nanoparticles (SiO2 NPs) are widely utilized in biomedicine due to their controllable size and biocompatibility. While previous studies have demonstrated that prenatal exposure to SiO2 NPs can traverse the placental barrier and induce neurotoxicity in offspring. However, their reproductive toxicity remains unclear. Here, it is found that prenatal SiO2 NPs exposure led to subfertility in female offspring, evidenced by decreased ovulation potential, ovarian reserve, and litter size. In contrast, male offspring maintained normal sperm production and fertility. Mechanistic analyses revealed that prenatal SiO2 NPs exposure disrupted meiotic recombination and increased oocyte apoptosis, resulting in reduced postnatal primordial follicle formation in females. Conversely, meiotic recombination occurring postnatally in male offspring remained unaffected. Notably, treatment with carboxylate (COOH)‐functionalized SiO2 nanoparticles (SiO2‐COOH NPs) has a minimal impact on fertility in female offspring. Further research, including clinical studies, is needed to confirm these findings in humans. These findings demonstrated gender‐specific reproductive toxicity induced by prenatal SiO2 NPs exposure and highlighted the importance of considering nanoparticle safety in prenatal contexts. Prenatal exposure to silicon dioxide nanoparticles (SiO2 NPs) caused subfertility in female offspring, reducing ovulation, ovarian reserve, and litter size, while male offspring remained unaffected. Mechanistic analysis revealed disrupted meiotic recombination and increased oocyte apoptosis in females. COOH‐functionalized SiO2 NPs showed minimal impact on fertility.

Different types of drivers usually take on different driving tendency on urban road, based on the diversity of driving tendency, a new two-lane cellular automaton model was proposed under condition of periodical boundary. The mean speed, flow volume and lane-changing frequency under different lane-changing and deceleration rules were simulated. In the process of computational simulation, the fundamental diagrams of traffic flow under different rules were obtained by changing traffic flow density. Simulation results show that the proposed new rules can improve traffic flow volume and suppress traffic jam to a certain degree. Finally, the critical points were discussed to show the impact of lane-changing on traffic flow.

The Rate of Penetration (ROP) during drilling is nonstationary and exhibits coupled local fluctuations, which makes it challenging to model for accurate prediction. To address the challenge of modeling multi-scale temporal dependencies in drilling, this study introduces a hybrid TCN–Informer framework. It integrates the causal dilated Temporal Convolutional Network (TCN) for capturing short-term patterns with the Informer’s ProbSparse attention mechanism for modeling long-range dependencies. A comprehensive methodology is adopted, which includes a four-stage data preprocessing pipeline featuring per-well z-score standardization and label concatenation, a sliding-window training scheme to address cold-start issues, and an Optuna-based Bayesian search for hyperparameter optimization. The prediction performance of the models was evaluated across various input sequence lengths using the Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Coefficient of Determination (R2). The results show that the proposed TCN–Informer demonstrates superior performance compared to Informer, Long Short-Term Memory (LSTM), Gated Recurrent Unit (GRU), and Transformer. Furthermore, the predictions of the TCN–Informer respond more rapidly to abrupt changes in the ROP and yield smoother, more stable results during intervals of stable ROP, validating its effectiveness in capturing both local and global temporal patterns.