A novel fluorescent probe for viscosity and polarity detection in real tobacco root cells and biological imaging.

The disruption of lipid droplet function is associated with the pathogenesis of various diseases. Clarifying the response behavior of lipid droplets to the microenvironment at the cellular level is of great significance. Plant lipids not only exist in phospholipids in cell membranes, but also in aromatic essential oils. Monitoring the level of lipid droplets in plant cells using fluorescent probes provides a simple method for screening lipid-rich varieties. We synthesized a polarity-viscosity responsive coumarin fluorescent probe, Cou-CN, which achieved sensitive detection of polarity and viscosity in dilute solution environments by constructing this simple probe with ICT and TICT properties and verifying it using Gaussian computational simulation. Cou-CN exhibited good lipid droplet illumination effects in HepG2 cells with a correlation coefficient of 0.92 compared to the commercial lipid droplet dye BODIPY. Additionally, co-staining the probe with the lipophilic commercial dye Nile Red in tobacco root stem seedling cells resulted in a high correlation coefficient of 0.9.

Advanced nano delivery system for stem cell therapy for Alzheimer's disease.

Alzheimer's Disease (AD) represents one of the most significant neurodegenerative challenges of our time, with its increasing prevalence and the lack of curative treatments underscoring an urgent need for innovative therapeutic strategies. Stem cells (SCs) therapy emerges as a promising frontier, offering potential mechanisms for neuroregeneration, neuroprotection, and disease modification in AD. This article provides a comprehensive overview of the current landscape and future directions of stem cell therapy in AD treatment, addressing key aspects such as stem cell migration, differentiation, paracrine effects, and mitochondrial translocation. Despite the promising therapeutic mechanisms of SCs, translating these findings into clinical applications faces substantial hurdles, including production scalability, quality control, ethical concerns, immunogenicity, and regulatory challenges. Furthermore, we delve into emerging trends in stem cell modification and application, highlighting the roles of genetic engineering, biomaterials, and advanced delivery systems. Potential solutions to overcome translational barriers are discussed, emphasizing the importance of interdisciplinary collaboration, regulatory harmonization, and adaptive clinical trial designs. The article concludes with reflections on the future of stem cell therapy in AD, balancing optimism with a pragmatic recognition of the challenges ahead. As we navigate these complexities, the ultimate goal remains to translate stem cell research into safe, effective, and accessible treatments for AD, heralding a new era in the fight against this devastating disease.

Transformation of dissolved organic matter leached from biodegradable and conventional microplastics under UV/chlorine treatment and the subsequent effect on contaminant removal.

The ultraviolet (UV)/chlorine process has been widely applied for water treatment. However, the transformation of microplastic-leached dissolved organic matter (MP-DOM) in advanced treatment of real wastewater remains unclear. Here, we investigated alterations in the photoproperties of MP-DOM leached from biodegradable and conventional microplastics (MPs) and their subsequent effects on the degradation of sulfamethazine (SMT) by the UV/chlorine process. Spectroscopy was used to assess photophysical properties, focusing on changes in light absorption capacity, functional groups, and fluorescence components, while photochemical properties were determined by calculating the apparent quantum yields of reactive intermediates (ΦRIs). For photophysical properties, our findings revealed that the degree of molecular structure modification, functional group changes, and fluorescence characteristics during UV/chlorine treatment are closely linked to the type of MPs. For photochemical properties, the ΦRIs increased with higher chlorine dosages due to the formation of new functionalities. Both singlet oxygen (1O2) and hydroxyl radicals (•OH) formation were strongly correlated with excited triplet state of DOM (3DOM*) in the UV/chlorine treatment. Additionally, we found that the four types of MP-DOM inhibit the degradation of SMT and elucidated the mechanisms behind this inhibition. We also proposed degradation pathways for SMT and assessed the ecotoxicity of the resulting intermediates. This study provides important insights into how the characteristics and transformation of MP-DOM affect contaminant degradation, which is critical for evaluating the practical application of UV-based advanced oxidation processes (UV-AOPs).

LightGBM integration with modified data balancing and whale optimization algorithm for rock mass classification.

The accurate prediction of uneven rock mass classes is crucial for intelligent operation in tunnel-boring machine (TBM) tunneling. However, the classification of rock masses presents significant challenges due to the variability and complexity of geological conditions. To address these challenges, this study introduces an innovative predictive model combining the improved EWOA (IEWOA) and the light gradient boosting machine (LightGBM). The proposed IEWOA algorithm incorporates a novel parameter l for more effective position updates during the exploration stage and utilizes sine functions during the exploitation stage to optimize the search process. Additionally, the model integrates a minority class technique enhanced with a random walk strategy (MCT-RW) to extend the boundaries of minority classes, such as Classes II, IV, and V. This approach significantly improves the recall and F1-score for these rock mass classes. The proposed methodology was rigorously evaluated against other predictive algorithms, demonstrating superior performance with an accuracy of 94.74%. This innovative model not only enhances the accuracy of rock mass classification but also contributes significantly to the intelligent and efficient construction of TBM tunnels, providing a robust solution to one of the key challenges in underground engineering.

The role of S-palmitoylation of C4BPA in regulating murine sperm motility and complement resistance.

The epididymis and epididymosomes are crucial for regulating sperm motility, a key factor in male fertility. Palmitoylation, a lipid modification involving the attachment of palmitic acid to cysteine residues, is essential for protein function and localization. Additionally, this modification plays a vital role in the sorting of proteins into exosomes. This study investigates the role of S-palmitoylation at the Cys15 residue of the C4b binding protein alpha chain (C4BPA) in murine sperm motility. Our findings revealed high expression of C4BPA mRNA in the caput epididymis, with the protein present across all regions of the epididymis. Palmitoylation of C4BPA in epididymal epithelial cells was essential for its enrichment in epididymosomes and on sperm, thereby maintaining sperm motility. Inhibition of palmitoylation significantly reduced sperm motility and the localization of C4BPA on sperm. Additionally, palmitoylated C4BPA in exosomes resisted complement C4 attacks, preserving motility, unlike mutated C4BPA (C15S). These results highlight the critical role of palmitoylated C4BPA in protecting sperm from complement attacks and maintaining motility, suggesting that reversible palmitoylation of epididymal proteins could be explored as a therapeutic strategy for male contraception. Our study underscores the importance of post-translational modifications in sperm function and presents new insights into potential male contraceptive methods.

A polar viscosity-sensitive fluorescent probe with large Stokes shifts for simultaneous imaging of lipid droplets and lysosomes in tobacco leaf vein cells and biological systems.

Lipid droplets (LDs) and lysosomes were dynamic organelles present in most eukaryotic cells that were interconnected and worked closely together to ensure the smooth physiological activities of organisms. The interaction between lipid droplets and lysosomes was thought to play a role in the development of certain diseases. In this paper we designed and synthesised a lipid droplet lysosomal probe. The Nap-Lyso-Ph-OH probe was constructed according to the ICT mechanism and exhibited sensitivity to both polarity and viscosity. The probe exhibited low cytotoxicity, a large Stokes shift, excellent selectivity and photostability. The probe was successfully used for labelling and imaging of lipid droplets and lysosomes in cells and zebrafish. Interestingly, we used tobacco seedling cells to explore the ability of Nap-Lyso-Ph-OH for imaging lipid droplet labelling in plant cells.

Long-term exposure to environmental concentration of dinotefuran disrupts ecdysis and sex ratio by dysregulating related gene expressions in Chironomus kiinensis.

Introduction: Currently, although there have been a few reports on the endocrine-disrupting effects of neonicotinoids, the effect on Chironomidae during long-term exposure remains unknown. Methods: Ecdysis and sex ratio, along with ecdysone-relevant gene expressions of representative neonicotinoid dinotefuran on Chironomus kiinensis were investigated at different environmental concentrations by long-term exposure. Results: A low dose of dinotefuran delayed pupation and emergence via inhibiting ecdysis. Sex ratios of adults shifted toward male-dominated populations with the concentration of dinotefuran increasing. The corresponding transcriptions of ecdysis genes ecr, usp, E74, and hsp70 were significantly downregulated in the midge. For estrogen effects, the vtg gene expression was upregulated, but there was no significant change for the err gene. Discussion: These results would improve our understanding of the endocrine-disrupting mechanisms of neonicotinoid insecticides to Chironomidae and provide data support for assessing their potential environmental risks.

To explore the postoperative nutritional status and factors influencing prognosis in patients with chronic constipation complicated by malnutrition.

Background: Many patients with constipation also suffer from varying degrees of malnutrition, and the relationship between the two conditions is a vicious cycle. Surgery is the final step in the treatment of constipation, with a success rate of up to 95%. This study aims to investigate the effects of surgical treatment on the nutritional status of patients with chronic constipation and malnutrition. Methods: A total of 60 patients with chronic constipation and various degrees of malnutrition who underwent surgery in our department from January 2020 to March 2023 were included in this study. Biochemical tests including BMI, albumin, total protein, hemoglobin, cholesterol and lymphocyte count were conducted, as well as measurements of inflammatory markers such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and C-reactive protein (CRP). Additionally, multiple nutritional risk screening scales (NRS2002, MUST, NRI, and MNA) and the prognostic nutritional index (PNI) were used to assess the nutritional status of patients before surgery, as well as at 1 month, 3 months, and 6 months post-surgery. Finally, we analyzed the factors influencing postoperative recovery outcomes in patients. Results: Compared to pre-operation, the BMI of patients significantly increased at 1 month, 3 months, and 6 months after the operation, with statistically significant differences (p < 0.001). Multiple nutritional risk assessment tools (NRS2002, MUST, NRI, and MNA), as well as the prognostic nutritional index (NPI), indicated a reduction in nutritional risk and improvement in nutritional status at 1, 3, and 6 months post-surgery, compared to pre-surgery levels (p < 0.001). The levels of albumin, total protein, and hemoglobin in patients at 1, 3, and 6 months after the surgery were significantly higher than those before the surgery (p < 0.001). However, there was no significant change in the number of lymphocytes. Inflammatory markers such as IL-6, IL-8, and CRP exhibited a significant decrease after the surgery, reaching normal levels at 6 months post-surgery (p < 0.001). Low BMI, low PNI, and low cholesterol levels are independent risk factors for patient prognosis (p < 0.05). Conclusion: Surgical treatment can enhance the nutritional status of constipation patients with malnutrition, which in turn promotes the restoration of intestinal motility. The patient's nutritional status will impact the postoperative recovery outcomes.

Network pharmacology screening, in vitro and in vivo evaluation of antianxiety and antidepressant drug-food analogue.

BACKGROUND: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties. PURPOSE: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs. STUDY DESIGN: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments. METHODS: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations. RESULTS: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes. CONCLUSION: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.

Synergistic Elimination of Chlorophenols Using a Single-Atom Nickel with Single-Walled Carbon Nanotubes: The Roles of Adsorption, Hydrodechlorination, and the Electro-Fenton Process.

Electrocatalytic degradation enables the efficient treatment of chlorinated pollutants (COPs); however, its application has been significantly hindered by the large amounts of unsafe intermediate products. In this study, we present a single-atom nickel with single-walled carbon nanotubes (SWCNTs) as an electrochemical reactor for the complete elimination of chlorophenols. Distinct products and reductive mechanisms were observed for Ni-N-C compared to Cu-N-C. Ni-N-C incorporation has a novel degradation pathway for efficient chlorophenol degradation involving hydrodechlorination and the electro-Fenton process. Most importantly, the weak adsorption between the chlorophenols and the SWCNTs promoted their dechlorination by the attached active atomic hydrogen (H*) formed on the Ni-N-C. Meanwhile, the SWCNTs improved the reduction of O2 to H2O2, which was subsequently decomposed by Ni-N-C to form hydroxyl radicals (·OH) for phenol oxidation. As a result, the degradation rate of 4-chlorophenol was increased by 5 and 10 times compared with those of the Ni-N-C and SWCNTs alone, respectively. The first-order reaction rate constant was 2.7 h-1, and the metal mass kinetics constant was 1956.5 min-1g-1. Aromatic COPs containing benzene rings could be degraded, but chloroacetic acids could not. This study demonstrates a new design for multifunctional electrochemical degradation that functions via dechlorination and the ·OH activation mechanism.

Synergistic interaction between brassinosteroid and jasmonate pathways in rice response to cadmium toxicity.

Brassinosteroids (BRs) and jasmonic acid (JA) are known to be involved in regulating plant responses to cadmium (Cd) stress. However, their specific roles and interaction in this process remain unclear. In this study, we discovered that exogenous BR alleviated Cd-mediated growth inhibition of rice seedlings. Enhanced Cd tolerance was also observed in m107, a BR-overproduction mutant. Phenotypic analysis of genetic materials involved in BR signaling confirmed the positive role of BR in regulating rice response to Cd toxicity. OsDLT, a key component in the BR signaling pathway, was found to be crucial for BR-mediated Cd tolerance. Further analysis demonstrated that activation of the BR pathway reduced the accumulation of Cd and reactive oxygen species (ROS) by modulating the expression of genes associated with Cd transport and ROS scavenging. Interestingly, transcriptome analysis indicated that the JA pathway was enriched in OsDLT-regulated differently expressed genes (DEGs). Gene expression and hormone assays showed that BR promoted the expression of JA pathway genes and JA levels in plants. Moreover, BR-induced tolerance was compromised in the JA signaling-deficient mutant osmyc2, suggesting that BR-mediated Cd resistance depends on the activation of the JA signaling pathway. Overall, our study revealed the synergistic interaction between BR and JA pathways in rice response to Cd stress, providing insights into the complex hormonal interplay in plant tolerance to heavy metals.

Spatiotemporal drivers of agricultural non-point source pollution: A case study of the Huang-Huai-Hai Plain, China.

Agricultural non-point source pollution (ANPSP) poses a severe threat to ecological environments, especially in China's major grain-producing regions. Despite the increasing attention, existing studies often overlook the spatial heterogeneity and driving mechanisms of ANPSP within different functional regions. This study addresses this research gap by constructing a bottom-up regional inventory of ANPSP for the Huang-Huai-Hai Plain (HHHP) and applying the Logarithmic Mean Divisia Index (LMDI) decomposition method to analyse the spatio-temporal patterns of ANPSP from 2000 to 2020. Spatial econometric models were further applied to examine the spatial spillover effects of driving factors from the perspective of Major Function-oriented Zoning (MFZ). The results show that while ANPSP emissions in the HHHP have generally increased over the past two decades, a slight decrease has been observed since 2015. Grain yield capacity and cropping intensity were identified as the primary drivers of ANPSP growth, particularly in urbanised zones (UZs) and main agricultural production zones (MAPZs). The study also highlights significant spatial heterogeneity in the impact of driving factors on ANPSP across different MFZs, with marked differences in both the direct and spatial spillover effects of these factors. This underlines the need for differentiated environmental protection policies tailored to the functions and characteristics of each region. By integrating the LMDI decomposition method with spatial econometric models, this study offers a new framework for understanding the ANPSP dynamics within the context of MFZs, providing policymakers with valuable insights for designing effective, regionally coordinated governance strategies.

Single-incision Retroperitoneal Laparoscopic Resection of Adrenal Tumors in Children.

BACKGROUND: We describe our experience with single-incision retroperitoneal laparoscopic (SIRL) for resection of adrenal tumors in pediatric patients and discuss the technique's clinical value. METHODS: We retrospectively analyzed clinical data of 27 pediatric patients who underwent SIRL between January 2020 and September 2023. Patients with tumors >5 cm in size and those requiring vascular skeletonization surgery or extensive lymph node dissection were excluded. Demographic, perioperative, and prognostic data were collected, and computed tomography (CT) and magnetic resonance imaging were used for preoperative tumor assessment. RESULTS: Of 27 patients, 16 were male and 11 were female; mean age 54 ± 45 months and mean body mass index 17.2 ± 3.6 kg/m2. Mean tumor length, width, and height were 4.1 ± 1.8 cm, 3.3 ± 2.1 cm, and 2.9 ± 1.7 cm, respectively. One patient experienced a diaphragmatic tear, three patients incurred peritoneal damage, and one patient developed postoperative renal artery injury, leading to thrombosis and renal atrophy. No surgery was converted to open surgery, and no intraoperative or postoperative blood transfusions were required. Operative time, blood loss, and postoperative dietary recovery time were satisfactory. No local recurrence or distant metastases were detected during the 6-48 months of follow-up involving outpatient and telephone assessments. CONCLUSIONS: Application of SIRL in pediatric patients with adrenal tumors achieved favorable clinical outcomes with an effective, minimally invasive surgical option for treating children with adrenal tumors. This technique demands a high level of surgical expertise, specialized instruments and experienced surgeons. Our findings indicate that SIRL is safe and provides significant postoperative benefits in pediatric patients. LEVEL OF EVIDENCE: Level IV.

Candidaemia: A 9-Year Retrospective Analysis of Epidemiology and Antimicrobial Susceptibility in Tertiary Care Hospitals in Western China.

Purpose: This investigation endeavors to scrutinize the resistance profiles to antifungal agents, alongside the clinical distribution of Candida isolates that yielded positive results in blood cultures at Suining Central Hospital spanning the years 2015 to 2023. The objective is to provide crucial epidemiological insights that may aid in early clinical intervention and judicious deployment of antifungal therapies. Methods: This retrospective analysis analyses data on 182 different Candida strains with positive clinical blood cultures obtained from the Microbiology Laboratory of Suining Central Hospital over a period of nine consecutive years. The study involved identification of Candida species and assessment of resistance patterns to fungal drugs. Results: Our analysis revealed that the median age of patients diagnosed with Candidaemia from the 182 strains was 62 years, with a distribution of 63.7% females and 36.3% males. Within the cohort of 182 Candida strains, Candida albicans constituted 32.4%, while non-albicans Candida species comprised 67.6% of the cases. Specifically, Candida tropicalis represented 37.4%, Candida glabrata 12.1%, Candida parapsilosis 11.0%,Candida guilliermondii 3.8%, and both Candida krusei and Candida Dublin accounted for 1.6% each. These Candida species were predominantly identified in intensive care units (ICU), hematology, gastroenterology, neurology centers, and endocrine metabolism units. Conclusion: The findings of this investigation suggest a shift in the prevalence of non-Candida albicans species, notably C. tropicalis, as the predominant cause of Candidaemia at Suining Central Hospital, surpassing C. albicans. Although instances of antifungal resistance are infrequent, there has been a notable rise in resistance to azoles. This study provides important insights into the local epidemiology, which will be essential for informing the selection of empirical antifungal therapy and contributing to the global surveillance of antifungal resistance.

Effect of excitation voltage in a magnetically induced electric field on the physicochemical, structural and functional properties of citrus pectin.

Treatment with a magnetic induced electric field (MIEF) under acidic conditions has proven to be an effective method for modifying pectin, enhancing its functional attributes. In this study, the effects of varying excitation voltages of MIEF under acidic conditions on the physicochemical, structural, and functional properties of citrus pectin (CP) were explored. The results demonstrated that compared to CP without MIEF treatment, MIEF-treated CP exhibited enhanced thermal stability, rheological behavior, emulsifying and gel-forming abilities, and antioxidant capacity. These improvements were attributed to higher degrees of esterification, reduced molecular weights, and increased levels of galacturonic acid and homogalacturonan in the structural backbone of the treated CP. Additionally, MIEF treatment under acidic conditions altered the surface morphology and crystalline structure of CP. Therefore, our findings suggest that applying moderate excitation voltages (150-200 V) during MIEF treatment can enhance the functional properties of CP, leading to the production of high-quality modified pectin.

Anti-bacterial effects, and metabolites derived from bifidobacterial fermentation of an exopolysaccharide of Cs-HK1 medicinal fungus.

This study was to investigate the antibacterial effects and metabolites derived from bifidobacterial fermentation of an exopolysaccharide EPS-LM produced by a medicinal fungus Cordyceps sinensis, Cs-HK1. EPS-LM was a partially purified polysaccharide fraction which was mainly composed of Man, Glc and Gal at 7.31:12.95:1.00 mol ratio with a maximum molecular weight of 360 kDa. After fermentation of EPS-LM in two bifidobacterial cultures, B. breve and B. longum, the culture digesta showed significant antibacterial activities, inhibiting the proliferation and biofilm formation of Escherichia coli. Based on untargeted metabolomic profiling of the digesta, the levels of short chain fatty acids, carboxylic acids, benzenoids and their derivatives were all increased significantly (p < 0.01), which probably contributed to the enhanced antibacterial activity by EPS-LM. Since EPS-LM was only slightly consumed for the bifidobacterial growth, it mainly stimulated the biosynthesis of bioactive metabolites in the bifidobacterial cells. The results also suggested that EPS-LM polysaccharide may have a regulatory function on the bifidobacterial metabolism leading to production of antibacterial metabolites, which may be of significance for further exploration.

Study on unseating prevention for multi-union long simply supported girder bridges under near-fault ground motions.

Girder shifting is a common form of seismic damage for girder bridges. Unseating could occur when the displacement of the girder is too large, especially for bridges near faults, because the velocity impulse effect leads to greater displacement responses of structures. Setting metal dampers between girders and piers is a useful way to control the seismic behavior and reduce the risk of unseating. Since metal dampers are inevitably exposed to the erosive service environments, their mechanical properties may degrade due to corrosion. In this paper, a U-shaped metal damper made of stainless steel instead of mild steel (i.e., U-shaped stainless steel damper, which could be named simply as USSSD) is proposed and applied to the seismic reduction design of girder bridges. First, the finite element model (FEM) of the USSSD is built by the ABAQUS, and its force-displacement relationship is obtained based on the skeleton curve, which is fitted by the trilinear kinematic strengthening model. Then, a multi-union long simply supported girder bridge is taken as an example. The FEM of the adopted bridge is established via the Midas Civil to verify the seismic mitigation effect of the proposed USSSD excited by near-fault ground motions. The numerical analyses demonstrate that the unseating may occur without the use of the USSSDs. The relative displacement between the girder and pier is effectively controlled by the USSSDs, and the reduction is more than 50 %. When the bridge is equipped with the USSSDs, both the curvature ductility coefficient of the pier bottom and the maximum drift of the pier tip increase by a limited amplitude, which do not cause additional damage to the piers.

Hsa_circ_0087784 enhances non-small cell lung cancer progression via the miR-576-5p/CDCA4 axis.

BACKGROUND: Circular RNAs (circRNAs) belong to a family of covalently closed single-stranded RNAs that have been implicated in cancer progression. Previous studies have reported that hsa_circ_0087784 was abnormally expressed in breast cancer. However, the role of hsa_circ_0087784 in non-small cell lung cancer (NSCLC) is unknown. METHODS: Here, we used RT-qPCR and FISH to examine hsa_circ_0087784 expression in NSCLC cells and tissue samples. The dual-luciferase reporter assay was used to identify downstream targets of hsa_circ_0087784. Transwell migration, 5-ethynyl-2´-deoxyuridine, and CCK-8 assays were used to examine migration and proliferation. Tumorigenesis and metastasis assays were used to determine the role of hsa_circ_0087784 in NSCLC progression in a mouse tumor xenograft model in vivo. RESULTS: We found that hsa_circ_0087784 was expressed at significantly high levels in NSCLC tissue samples and cell lines. Downregulation of hsa_circ_0087784 suppressed NSCLC cellular proliferation, as well as migration. Our dual-luciferase reporter assay revealed that miR-576-5p and CDCA4 were downstream targets of hsa_circ_0087784. CDCA4 overexpression or miR-576-5p suppression reversed the effects of hsa_circ_0087784 silencing on NSCLC cell migration, and EMT-related protein expression levels. CONCLUSION: Our findings suggested that downregulation of hsa_circ_0087784 inhibited NSCLC metastasis and progression through the regulation of CDCA4 expression and miR-576-5psponging.

Development and validation of machine-learning models of diet management for hyperphenylalaninemia: a multicenter retrospective study.

BACKGROUND: Assessing dietary phenylalanine (Phe) tolerance is crucial for managing hyperphenylalaninemia (HPA) in children. However, traditionally, adjusting the diet requires significant time from clinicians and parents. This study aims to investigate the development of a machine-learning model that predicts a range of dietary Phe intake tolerance for children with HPA over 10 years following diagnosis. METHODS: In this multicenter retrospective observational study, we collected the genotypes of phenylalanine hydroxylase (PAH), metabolic profiles at screening and diagnosis, and blood Phe concentrations corresponding to dietary Phe intake from over 10 years of follow-up data for 204 children with HPA. To incorporate genetic information, allelic phenotype value (APV) was input for 2965 missense variants in the PAH gene using a predicted APV (pAPV) model. This model was trained on known pheno-genotype relationships from the BioPKU database, utilizing 31 features. Subsequently, a multiclass classification model was constructed and trained on a dataset featuring metabolic data, genetic data, and follow-up data from 3177 events. The final model was fine-tuned using tenfold validation and validated against three independent datasets. RESULTS: The pAPV model achieved a good predictive performance with root mean squared error (RMSE) of 1.53 and 2.38 on the training and test datasets, respectively. The variants that cause amino acid changes in the region of 200-300 of PAH tend to exhibit lower pAPV. The final model achieved a sensitivity range of 0.77 to 0.91 and a specificity range of 0.8 to 1 across all validation datasets. Additional assessment metrics including positive predictive value (0.68-1), negative predictive values (0.8-0.98), F1 score (0.71-0.92), and balanced accuracy (0.8-0.92) demonstrated the robust performance of our model. CONCLUSIONS: Our model integrates metabolic and genetic information to accurately predict age-specific Phe tolerance, aiding in the precision management of patients with HPA. This study provides a potential framework that could be applied to other inborn errors of metabolism.