Developing liver-targeted naringenin nanoparticles for breast cancer endocrine therapy by promoting estrogen metabolism.

Endocrine therapy is standard for hormone receptor-positive (HR+) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention to estradiol metabolism in the liver and is usually challenged by treatment failure. In a previous study, we demonstrated that the natural compound naringenin (NAR) inhibited HR+ breast cancer growth by activating estrogen sulfotransferase (EST) expression in the liver. Nevertheless, the poor water solubility, low bio-barrier permeability, and non-specific distribution limited its clinical application, particularly for oral administration. Here, a novel nano endocrine drug NAR-cell penetrating peptide-galactose nanoparticles (NCG) is reported. We demonstrated that NCG presented specific liver targeting and increased intestinal barrier permeability in both cell and zebrafish xenotransplantation models. Furthermore, NCG showed liver targeting and enterohepatic circulation in mouse breast cancer xenografts following oral administration. Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR+ breast cancer.

Brain-Targeted Black Phosphorus-Based Nanotherapeutic Platform for Enhanced Hypericin Delivery in Depression.

Depression is a significant global health concern that remains inadequately treated due to the limited effectiveness of conventional drug therapies. One potential therapeutic agent, hypericin (HYP), is identified as an effective natural antidepressant. However, its poor water solubility, low bioavailability, and limited ability to penetrate the brain parenchyma have hindered its clinical application. To address these shortcomings and enhance the therapeutic efficacy of HYP, it is loaded onto black phosphorus nanosheets (BP) modified with the neural cell-targeting peptide RVG29 to synthesize a nanoplatform named BP-RVG29@HYP (BRH). This platform served as a nanocarrier for HYP and integrated the advantages of BP with advanced delivery methods and precise targeting strategies. Under the influence of 808 nm near-infrared irradiation (NIR), BRH effectively traversed an in vitro BBB model. In vivo experiments validated these findings, demonstrating that treatment with BRH significantly alleviated depressive-like behaviors and oxidative stress in mice. Importantly, BRH exhibited an excellent safety profile, causing minimal adverse effects, which highlighted its potential as a promising therapeutic agent. In brief, this novel nanocarrier holds great promise in the development of antidepressant drugs and can create new avenues for the treatment of depression.

Combined Remediation Effects of Sewage Sludge and Phosphate Fertilizer on Pb-Polluted Soil from a Pb-Acid Battery Plant.

Pb soil pollution poses a serious health risk to both the environment and humans. Immobilization is the most common strategy for remediation of heavy metal polluted soil. In this study, municipal sewage sludge was used as an amendment for rehabilitation of Pb-contaminated soils, for agricultural use, near a lead-acid battery factory. The passivation effect was further improved by the addition of phosphate fertilizer. It was found that the leachable Pb content in soils was decreased from 49.6 mg kg-1 to 16.1-36.6 mg kg-1 after remediation of sludge for 45 d at applied dosage of municipal sewage sludge of 4-16 wt%, and further decreased to 14.3-34.3 mg kg-1 upon extension of the remediation period to 180 d. The addition of phosphate fertilizer greatly enhanced the Pb immobilization, with leachable Pb content decreased to 2.0-23.6 mg kg-1 with increasing dosage of phosphate fertilizer in range of 0.8-16 wt% after 180 d remediation. Plant assays showed that the bioavailability of Pb was significantly reduced by the soil remediation, with the content of absorbed Pb in mung bean roots decreased by as much as 87.0%. The decrease in mobility and biotoxicity of the soil Pb is mainly attributed to the speciation transformation of carbonate, Fe-Mn oxides and organic matter bound Pb to residue Pb under the synergism of reduction effect of sludge and acid dissolution and precipitation effect of phosphate fertilizer. This study suggests a new method for remediation of Pb-contaminated soil and utilization of municipal sewage sludge resources.

Polycationic Open-Shell Cyclophanes: Synthesis of Electron-Rich Chiral Macrocycles, and Redox-Dependent Electronic States.

π-Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main-group electron-donating carbazolyl moieties or the π-expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure-of-eight topology as a result of the conjugation patterns of 2,2',7,7'-spirobifluorenyl in 1 and triarylamine-coupled aza[7]helicene-based building blocks in 2. This electronic nature of redox-active, carbazole-rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open-shell cyclophanes. Their redox-dependent electronic states of the resulting multispin polyradicals have been characterized by VT-ESR, UV/Vis-NIR absorption and spectroelectrochemical measurements. The singlet (ΔES-T=-1.29 kcal mol-1) and a nearly degenerate singlet-triplet ground state (ΔES-T(calcd)=-0.15 kcal mol-1 and ΔES-T(exp)=0.01 kcal mol-1) were proved for diradical dications 12+2⋅ and 22+2⋅, respectively. Our work provides an experimental proof for the construction of electron-donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors.

Directly Self-Assembly of Aligned Ag NWs Films at the Air-Water Interface for the Detection of Pathogens in Artificial Breath Aerosols.

Exhaled aerosols from humans, containing various pathogens, are crucial for early disease diagnosis. However, the traditional pathogen detection methods, such as polymerase chain reaction, are often slow and cumbersome due to complex sampling and procedures. This study introduces a novel, direct, and label-free detection method for pathogens in respiratory aerosols, utilizing a highly aligned silver nanowire (Ag NW) film combined with a filter membrane (Ag NWs@filter) as a surface-enhanced Raman spectroscopy-active substrate. A large-scale, ordered silver nanowire film was developed through a simplified self-assembly process. This process eliminates the need for an organic phase and complex surface modifications of Ag NWs, which are common in other preparation methods. Subsequently, the fabricated Ag NWs@filter demonstrated its capability to continuously capture and efficiently preconcentrate pathogens from aerosols, achieving a remarkable detection limit of 3 × 103 CFU/mL, demonstrated using Escherichia coli (E. coli) as a model pathogen. Moreover, the classification between E. coli and Pseudomonas aeruginosa achieved an overall accuracy of 96.5% by the principal component analysis with linear discriminant analysis models. The success of this sensing strategy illustrates its potential in detecting and identifying a variety of biomarkers present in respiratory aerosols, marking a significant step forward in the field of pathogen detection.

Functional brain network alterations in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two highly prevalent and commonly co-occurring neurodevelopmental disorders. The neural mechanisms underpinning the comorbidity of ASD and ADHD (ASD + ADHD) remain unclear. We focused on the topological organization and functional connectivity of brain networks in ASD + ADHD patients versus ASD patients without ADHD (ASD-only). Resting-state functional magnetic resonance imaging (rs-fMRI) data from 114 ASD and 161 typically developing (TD) individuals were obtained from the Autism Brain Imaging Data Exchange II. The ASD patients comprised 40 ASD + ADHD and 74 ASD-only individuals. We constructed functional brain networks for each group and performed graph-theory and network-based statistic (NBS) analyses. Group differences between ASD + ADHD and ASD-only were analyzed at three levels: nodal, global, and connectivity. At the nodal level, ASD + ADHD exhibited topological disorganization in the temporal and occipital regions, compared with ASD-only. At the global level, ASD + ADHD and ASD-only displayed no significant differences. At the connectivity level, the NBS analysis revealed that ASD + ADHD showed enhanced functional connectivity between the prefrontal and frontoparietal regions, as well as between the orbitofrontal and occipital regions, compared with ASD-only. The hippocampus was the shared region in aberrant functional connectivity patterns in ASD + ADHD and ASD-only compared with TD. These findings suggests that ASD + ADHD displays altered topology and functional connectivity in the brain regions that undertake social cognition, language processing, and sensory processing.

Synthesis of π-Conjugated Chiral Aza/Boracyclophanes with a meta and para Substitution.

We herein describe the synthesis of a new class of axially chiral aza/boracyclophanes (BDN1, BXN1, BDB1 and BXB1) using binaphthyls as chiral building blocks and the main-group (B/N) chemistry with tunable electronic effects. All macrocycles substituted with triarylamine donors or triarylborane acceptors are strongly luminescent. These macrocycles showed two distinct meta and para π-conjugation pathways, leading to the formation of quasi figure-of-eight and square-shaped conformations. Interestingly, comparison of such structural models revealed that the former type of macrocycles BXN1 and BXB1 gave higher racemization barriers relative to the other ones. The results reported here may provide a new approach to engineer the optical stability of π-conjugated chiral macrocycles by controlling π-substitution patterns. The ring constraints induced by macrocyclization were also demonstrated to contribute to the configurational persistence as compared with the open-chain analogues p-BTT and m-BTT.

Ecological restoration affects the dynamic response of alkaline minerals dissolution in bauxite residue.

Regulating alkalinity is the key process to eliminating environmental risk and implementing sustainable management of bauxite residue. Nevertheless, continuous release of free alkali from the solid phase (mainly sodalite and cancrinite) is a major challenge for long-term stability of alkalinity in amended bauxite residue. In order to understand the dissolution behavior of sodalite and cancrinite, their dissolution kinetics under simulated pH conditions of 8, 9 and 10 were investigated. Additionally, PHREEQC software and shrinking core model (SCM) were employed to analyze the release pattern of saline ions. The results revealed that the ratio of Na/Si and Na/Al values exhibited greater stability in sodalite than in cancrinite. The dissolution of elemental Na, Si, and Al in sodalite and cancrinite was matched with non-chemometric characteristics. The kinetic calculations by the shrinking core model (SCM) suggested that both sodalite and cancrinite exhibited slow dissolution kinetics, and their dissolution processes belong to internal diffusion control and external diffusion control, respectively. pH controlled the dissolution kinetic rates of sodalite and cancrinite mainly by changing their coupled dissolution-precipitation processes. More importantly, these findings can predict the change of alkaline components accurately, thus facilitating the implementation of efficient alkalinity regulation strategies for the ecological restoration of bauxite residue disposal areas.

Confined-Enhanced Raman Spectroscopy.

In 1997, the discovery of single molecule-surface enhanced Raman spectroscopy (SM-SERS) rekindled broad interests owing to its ultrahigh enhancement factor up to the 1014-1015 level. However, regretfully, the advantage of SM-SERS with an ultralow detection limit has not yet been fully utilized in commercialized applications. Here, we report a strategy, which we name confined-enhanced Raman spectroscopy, in which the overall Raman properties can be remarkably improved with in situ-formed active nanoshell on the surface of silver or gold nanoparticles. The nanoshell can confine and anchor molecules onto the surface of plasmonic nanoparticles and avoid desorption from hot spots so that the "on and off" blinking effect can be eliminated. It is the first time the single-molecule detection of analytes with super sensitivity, high stability, and reproducibility based on gold nanoparticles has been realized. In addition, this strategy is suitable for SERS detection in diverse molecule systems, including biomedical diagnosis, catalytic reaction, etc.

Endocrine-disrupting chemicals and breast cancer: a meta-analysis.

Background: Globally, the burden of breast cancer has increased significantly in recent decades. Emerging evidence suggested that endocrine-disrupting chemicals (EDCs), which have the potential to interfere with the function of normal hormones, may play a crucial role in this trend. However, the potential relationships were inconsistent in various studies. Objective and search methods: In our study, we sought to fully evaluate the currently available epidemiological evidence to ascertain whether certain EDC congeners and their metabolites are related to breast cancer risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of original peer-reviewed publications in three electronic databases: PubMed, Web of Science, and Embase. Publications that covered xenobiotic EDC exposures and breast cancer-confirmed histological results or antecedent medical records or reporting to health registers were taken into consideration. Outcomes: The final result of the literature search was 6,498 references, out which we found 67 publications that matched the requirements for meta-analysis and eight publications for qualitative trend synthesis. In this meta-analysis, statistically significant associations revealed that (i) 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) were somewhat related to a greater risk of breast cancer. However, this relationship only existed in blood serum but not in adipose tissue. (ii) Breast cancer risk was increased by exposure to chlordane and hexachlorocyclohexane. (iii) Five polychlorinated biphenyls (PCB 99, PCB 105, PCB 118, PCB 138, and PCB 183) can increase the risk of breast cancer. (iv) One phthalate congener (BBP) and one per- and polyfluoroalkyl substance congener (PFDoDA) were negatively associated with breast cancer risk. Unfortunately, heterogeneity was not well explained in our review, and a limited number of available prospective studies investigating the associations between EDC exposure and breast cancer were included in our meta-analysis. To elucidate the overall associations, future large, longitudinal epidemiological investigations are needed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42023420927.

Plant-Derived Vesicles: A New Era for Anti-Cancer Drug Delivery and Cancer Treatment.

Lipid-structured vesicles have been applied for drug delivery system for over 50 years. Based on their origin, lipid-structured vesicles are divided into two main categories, namely synthetic lipid vesicles (SLNVEs) and vesicles of mammalian origin (MDVEs). Although SLNVEs can stably transport anti-cancer drugs, their biocompatibility is poor and degradation of exogenous substances is a potential risk. Unlike SLNVEs, MDVEs have excellent biocompatibility but are limited by a lack of stability and a risk of contamination by dangerous pathogens from donor cells. Since the first discovery of plant-derived vesicles (PDVEs) in carrot cell supernatants in 1967, emerging evidence has shown that PDVEs integrate the advantages of both SLNVEs and MDVEs. Notably, 55 years of dedicated research has indicated that PDVEs are an ideal candidate vesicle for drug preparation, transport, and disease treatment. The current review systematically focuses on the role of PDVEs in cancer therapy and in particular compares the properties of PDVEs with those of conventional lipid vesicles, summarizes the preparation methods and quality control of PDVEs, and discusses the application of PDVEs in delivering anti-cancer drugs and their underlying molecular mechanisms for cancer therapy. Finally, the challenges and future perspectives of PDVEs for the development of novel therapeutic strategies against cancer are discussed.

Si-Ni-San alleviates early life stress-induced depression-like behaviors in adolescence via modulating Rac1 activity and associated spine plasticity in the nucleus accumbens.

Background: Early life stress (ELS) is a major risk factor for depression in adolescents. The nucleus accumbens (NAc) is a key center of the reward system, and spine remodeling in the NAc contributes to the development of depression. The Si-Ni-San formula (SNS) is a fundamental prescription for treating depression in traditional Chinese medicine. However, little is known about the effects of SNS on behavioral abnormalities and spine plasticity in the NAc induced by ELS. Purpose: This study aimed to investigate the therapeutic effect and the modulatory mechanism of SNS on abnormal behaviors and spine plasticity in the NAc caused by ELS. Methods: We utilized a model of ELS that involved maternal separation with early weaning to explore the protective effects of SNS on adolescent depression. Depressive-like behaviors were evaluated by the sucrose preference test, the tail suspension test, and the forced swimming test; anxiety-like behaviors were monitored by the open field test and the elevated plus maze. A laser scanning confocal microscope was used to analyze dendritic spine remodeling in the NAc. The activity of Rac1 was detected by pull-down and Western blot tests. Viral-mediated gene transfer of Rac1 was used to investigate its role in ELS-induced depression-like behaviors in adolescence. Results: ELS induced depression-like behaviors but not anxiety-like behaviors in adolescent mice, accompanied by an increase in stubby spine density, a decrease in mushroom spine density, and decreased Rac1 activity in the NAc. Overexpression of constitutively active Rac1 in the NAc reversed depression-related behaviors, leading to a decrease in stubby spine density and an increase in mushroom spine density. Moreover, SNS attenuated depression-like behavior in adolescent mice and counteracted the spine abnormalities in the NAc induced by ELS. Additionally, SNS increased NAc Rac1 activity, and the inhibition of Rac1 activity weakened the antidepressant effect of SNS. Conclusion: These results suggest that SNS may exert its antidepressant effects by modulating Rac1 activity and associated spine plasticity in the NAc.

Assessing the role of central lymph node ratio in predicting recurrence in N1a low-to-intermediate risk papillary thyroid carcinoma.

Introduction: Lymph node metastasis in patients with papillary thyroid carcinoma (PTC) is associated with postoperative recurrence. Recently, most studies have focused on the evaluation of recurrence in patients with late-stage PTC, with limited data on those with early-stage PTC. We aimed to assess the relationship between lymph node ratio (LNR) and recurrence in low-to-intermediate-risk patients and validate its diagnostic efficiency in both structural (STR) and biochemical recurrence (BIR). Methods: Clinical data of patients with PTC diagnosed at the Affiliated Hospital of Jining Medical University were retrospectively collected. The optimal LNR cut-off values for disease-free survival (DFS) were determined using X-tile software. Predictors were validated using univariate and multivariate Cox regression analyses. Results: LNR had a higher diagnostic effectiveness than metastatic lymph nodes in patients with low-to-intermediate recurrence risk N1a PTC. The optimal LNR cutoff values for STR and BIR were 0.75 and 0.80, respectively. Multivariate Cox regression analysis showed that LNR≥0.75 and LNR≥0.80 were independent factors for STR and BIR, respectively. The 5-year DFS was 90.5% in the high LNR (≥0.75) and 96.8% in low LNR (<0.75) groups for STR. Regarding BIR, the 5-year DFS was 75.7% in the high LNR (≥0.80) and 86.9% in low LNR (<0.80) groups. The high and low LNR survival curves exhibited significant differences on the log-rank test. Conclusion: LNR was associated with recurrence in patients with low-to-intermediate recurrence risk N1a PTC. We recommend those with LNR≥0.75 require a comprehensive evaluation of lateral neck lymphadenopathy and consideration for lateral neck dissection and RAI treatment.

Si-Ni-San reverses dietary fat absorption defects in a murine model of depression.

Depression is often associated with fatigue/energy loss. However, we lack a detailed understanding of the factors explaining this association. In this study, we uncovered that depressed mice have a defect in fat absorption, resulting in weight loss and reduced circulating lipid levels. Si-Ni-San (SNS), a basic formula of traditional Chinese medicine (TCM) for the treatment of depression, was found to not only alleviate depression-like behaviors, but also reverse the weight loss and dietary fat absorption of depressed mice. We found that SNS improved body weight and circulating lipid levels of depressed mice by up-regulating proteins [such as FFA uptake protein (CD36), TAG synthesis proteins (GPAT3, MOGAT2, DGAT1 and DGAT2) and chylomicron packaging proteins (MTP and APOB)] in the fat absorption pathway. Furthermore, cell-based results conducted with LPS-stimulated mouse MODE-K and human Caco-2 cells support that SNS, as well as Sinensetin (SIN) and Nobiletin (NOB), the two active components of the formula, have a role in regulating lipid absorption. Mechanistic studies revealed that SNS reverses body weight and fat absorption defects of depressed mice in part through the NR1D1/BMAL1/DGAT2 axis. These findings advance our understanding of the crosstalk between depression and energy loss, highlight the importance of gut function in disease management, and provide a basis for the application of SNS in the clinical treatment of depression and related disorders.

The Effects of Early-Life Stress on Liver Transcriptomics and the Protective Role of EPA in a Mouse Model of Early-Life-Stress-Induced Adolescent Depression.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.

Chiral Luminescent Aza[7]helicenes Functionalized with a Triarylborane Acceptor and Near-Infrared-Emissive Doublet-State Radicals.

This paper presents new chiral luminescent molecules (N7-BMes2 and N7-TTM) using configurationally stable aza[7]helicene (1) as a universal heteroatom-doped chiral scaffold. The respective reactions of electron-donating 1 with a triarylborane acceptor via palladium-catalyzed Buchwald-Hartwig C-N coupling and with the open-shell doublet-state TTM radical via nucleophilic aromatic substitution (SN2Ar) resulted not only in tunable emissions from blue to the NIR domain but also in significantly enhanced emission quantum efficiency up to Φ = 50%.

Transoral and submental endoscopic thyroidectomy (TOaST) for early stage papillary thyroid carcinoma: a real-world data retrospective cohort study.

INTRODUCTION: Although transoral endoscopic thyroidectomy (TOETVA) is widely utilized in clinical practice, some problems and restrictions still remain. Our study compared the perioperative features and early surgical efficacy of TOETVA and a modified transoral and submental endoscopic thyroidectomy (TOaST) in early stage papillary thyroid carcinoma (PTC). METHODS: The clinical data of PTC patients who underwent endoscopic thyroidectomy, including 42 modified TOaST patients and 114 traditional TOETVA patients, were retrospectively collected. Propensity score matching was employed to reduce patient selection bias. The perioperative features and early surgical efficacy data of two groups were compared. RESULTS: The operation time of the TOaST group was significantly shorter than that of the TOETVA group (150.00 ± 35.47 min vs. 168.75 ± 44.49 min; P = 0.030). Furthermore, the TOaST group required shorter days for a normal diet (3.38 ± 0.93 days vs. 4.04 ± 1.03 days; P = 0.000) and a shorter hospital stay than the TOETVA group (5.85 ± 2.17 days vs. 6.12 ± 2.01 days; P = 0.003). There was no statistical difference in complications between the two groups, but the probability of numbness of the lower lip and chin in the TOaST group was lower than that in the TOETVA group(5.12% vs. 13.04%, P = 0.321). The symptoms of mandibular numbness and hoarseness of most patients were relieved in both groups 6 months after surgery, and no abnormalities and recurrence were found in the thyroid ultrasound. All the patients were satisfied with the appearance of their surgical incision. CONCLUSION: In early stage PTC patients, TOaST had the same surgical effectiveness as traditional TOETVA but can minimize the probability of mandibular numbness and improve the perioperative quality of life.

Nomogram to predict the risk of biochemical recurrence and structural recurrence in patients with stage cN1 papillary thyroid carcinoma.

INTRODUCTION: Although papillary thyroid carcinoma (PTC) is thought to be the least aggressive thyroid cancer, it has a significant recurrence rate. Therefore, we aimed to develop a nomogram to estimate the probability of biochemical recurrence (BIR) and structural recurrence (STR) in patients with stage cN1 PTC. METHODS: We studied the relationship between the characteristics of patients with stage N1a PTC and the risk of recurrence by analysing the data of 617 inpatients (training cohort) and 102 outpatients (validation cohort) in our hospital. We used the least absolute shrinkage and selection operator regression model to identify prognostic indicators to construct nomograms to predict the risk of BIR and STR. RESULTS: There were 94 (15.24%) BIR cases in the training cohort and 36 (35.29%) in the validation cohort. There were 31 (5.02%) STR cases in the training cohort and 23 (22.55%) cases in the validation cohort. The variables included in the BIR nomogram were sex, age at diagnosis, tumour size, extrathyroidal infiltration, and lymph node ratio (LNR). While the variables included in the STR nomogram were tumour size, extrathyroidal infiltration, BRAF state, metastatic lymph nodes, and LNR. Both the prediction models demonstrated good discrimination ability. The results showed the calibration curve of the nomogram was near the optimum diagonal line, and the decision curve analysis showed a noticeably better benefit. CONCLUSION: The LNR may be a valid prognostic indicator for patients with stage cN1 PTC. The nomograms could help clinicians identify high-risk patients and choose the best postsurgical therapy and monitoring.