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Abstract Pomacea canaliculata is one of the most successful invader in worldwide, adversely affecting native ecosystem through direct predation or indirect competition, while the mechanism of indirect effects on native species remain poorly understood. To clarify the effects of P. canaliculata on the native near-niche species, Bellamya purificata, a widespread freshwater gastropod in China, was selected as the research subject. The changes of mortality, histology, antioxidant system as well as the intestinal flora diversity of B. purificata were explored in present study. The results showed that the median lethal dose of P. canaliculata culture solution for B. purificata was 23.76 ind/L and a concentration-dependent damage of both the gonad and hepatopancreas were observed, the gonadal villi were dissolved and the hepatopancreas cells were broken at 20 ind/L. Furthermore, different concentrations of P. canaliculata culture solution leading to the antioxidant damage on the enzyme or non-enzyme systems of B. purificata at various degrees. Additionally, a decrease in the diversity of the intestinal flora was observed, accompanied by an increase in the abundance of pathogenic bacteria such as Pseudomonas and Aeromonas after the exposure of the culture solution of P. canaliculata. Last, after being recovered in freshwater for 24 h, the antioxidant damage of B. purificata and the disturbance of intestinal flora diversity were still not recovered especially in the high concentration group. The indirect competitive mechanism of P. canaliculata culture solution on B. purificata were explored from the aspects of tissue, biochemical level and intestinal flora, which enriched the research of P. canaliculata invasion on native snails in China, and provided new insights for the study of the invasion strategy of P. canaliculata.

The cuticular wax, acting as the ultimate defense barrier, is essential for the normal morphogenesis of plant organs. Despite this importance, the connection between wax composition and leaf development has not been thoroughly explored. In this study, we characterized a new maize mutant, ragged leaf4 (rgd4), which exhibits crinkled and ragged leaves starting from the sixth leaf stage. The phenotype of rgd4 is conferred by ZmCER1, which encoding an aldehyde decarbonylase involved in wax biosynthesis. ZmCER1 function deficient mutant displayed reduced cuticular wax density and disordered bulliform cells (BCs), while ZmCER1 overexpressing plants exhibited the opposite effects, indicating that ZmCER1 regulates cuticular wax biosynthesis and BCs development. Additionally, as the density of cuticular wax increased, the water loss rate of detached leaf decreases, suggesting that ZmCER1 is positively correlated with plant drought tolerance.

Abstract Pomacea canaliculata is one of the most notorious invasive aquatic snail, capable of influencing various aquatic organisms through their secretions. Limnodrilus hoffmeisteri and Propsilocerus akamusi are the most prevalent and powerful bioturbators in aquatic ecosystems. However, the mechanism of P. canaliculata's secretions affecting bioturbators remains unknown. This study aimed to investigate the effects of P. canaliculata's secretion on L. hoffmeisteri and P. akamusi. L. hoffmeisteri and P. akamusi were treated for 24 h with P. canaliculata and the native species Bellamya aeruginosa secretions at different densities (1 or 20). The migration numbers and aggregation rate of L. hoffmeisteri indicated that P. canaliculata secretion caused L. hoffmeisteri to become alert and migrate away from the nucleus community, resulting in poor population identification, especially at high concentrations. Moreover, the antioxidant enzymatic activity, lipid peroxidation, intestinal microbial diversity, and composition of the two bioturbators were analyzed. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were elevated following P. canaliculata secretion treatment, indicating oxidative damage. Furthermore, the composition and diversity of intestinal microbiota of L. hoffmeisteri and P. akamusi were changed. The abundance of functional microbiota decreased, and pathogenic bacteria such as Aeromonas became dominant in the intestines of both bioturbators. The current research evaluates the effects of P. canaliculata secretion on the behavior, oxidative stress, and intestinal microbial composition and diversity of two bioturbators, providing new insights into the assessment of post‐invaded ecosystems.

Abstract The persistent cereal endosperm constitutes the majority of the grain volume. Dissecting the gene regulatory network underlying cereal endosperm development will facilitate yield and quality improvement of cereal crops. Here, we use single-cell transcriptomics to analyze the developing maize (Zea mays) endosperm during cell differentiation. After obtaining transcriptomic data from 17,022 single cells, we identify 12 cell clusters corresponding to five endosperm cell types and revealing complex transcriptional heterogeneity. We delineate the temporal gene-expression pattern from 6 to 7 days after pollination. We profile the genomic DNA-binding sites of 161 transcription factors differentially expressed between cell clusters and constructed a gene regulatory network by combining the single-cell transcriptomic data with the direct DNA-binding profiles, identifying 181 regulons containing genes encoding transcription factors along with their high-confidence targets, Furthermore, we map the regulons to endosperm cell clusters, identify cell-cluster-specific essential regulators, and experimentally validated three predicted key regulators. This study provides a framework for understanding cereal endosperm development and function at single-cell resolution.

PurposeTo develop and validate a deep learning radiomics (DLR) model that uses X-ray images to predict the classification of osteoporotic vertebral fractures (OVFs).Material and methodsThe study encompassed a cohort of 942 patients, involving examinations of 1076 vertebrae through X-ray, CT, and MRI across three distinct hospitals. The OVFs were categorized as class 0, 1, or 2 based on the Assessment System of Thoracolumbar Osteoporotic Fracture. The dataset was divided randomly into four distinct subsets: a training set comprising 712 samples, an internal validation set with 178 samples, an external validation set containing 111 samples, and a prospective validation set consisting of 75 samples. The ResNet-50 architectural model was used to implement deep transfer learning (DTL), undergoing -pre-training separately on the RadImageNet and ImageNet datasets. Features from DTL and radiomics were extracted and integrated using X-ray images. The optimal fusion feature model was identified through least absolute shrinkage and selection operator logistic regression. Evaluation of the predictive capabilities for OVFs classification involved eight machine learning models, assessed through receiver operating characteristic curves employing the “One-vs-Rest” strategy. The Delong test was applied to compare the predictive performance of the superior RadImageNet model against the ImageNet model.ResultsFollowing pre-training separately on RadImageNet and ImageNet datasets, feature selection and fusion yielded 17 and 12 fusion features, respectively. Logistic regression emerged as the optimal machine learning algorithm for both DLR models. Across the training set, internal validation set, external validation set, and prospective validation set, the macro-average Area Under the Curve (AUC) based on the RadImageNet dataset surpassed those based on the ImageNet dataset, with statistically significant differences observed (P

Abstract Background Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. Methods The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. Results We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. Conclusions Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases. Graphical Abstract

Abstract Background We evaluated the diagnostic efficacy of deep learning radiomics (DLR) and hand-crafted radiomics (HCR) features in differentiating acute and chronic vertebral compression fractures (VCFs). Methods A total of 365 patients with VCFs were retrospectively analysed based on their computed tomography (CT) scan data. All patients completed MRI examination within 2 weeks. There were 315 acute VCFs and 205 chronic VCFs. Deep transfer learning (DTL) features and HCR features were extracted from CT images of patients with VCFs using DLR and traditional radiomics, respectively, and feature fusion was performed to establish the least absolute shrinkage and selection operator. The MRI display of vertebral bone marrow oedema was used as the gold standard for acute VCF, and the model performance was evaluated using the receiver operating characteristic (ROC).To separately evaluate the effectiveness of DLR, traditional radiomics and feature fusion in the differential diagnosis of acute and chronic VCFs, we constructed a nomogram based on the clinical baseline data to visualize the classification evaluation. The predictive power of each model was compared using the Delong test, and the clinical value of the nomogram was evaluated using decision curve analysis (DCA). Results Fifty DTL features were obtained from DLR, 41 HCR features were obtained from traditional radiomics, and 77 features fusion were obtained after feature screening and fusion of the two. The area under the curve (AUC) of the DLR model in the training cohort and test cohort were 0.992 (95% confidence interval (CI), 0.983-0.999) and 0.871 (95% CI, 0.805-0.938), respectively. While the AUCs of the conventional radiomics model in the training cohort and test cohort were 0.973 (95% CI, 0.955-0.990) and 0.854 (95% CI, 0.773-0.934), respectively. The AUCs of the features fusion model in the training cohort and test cohort were 0.997 (95% CI, 0.994-0.999) and 0.915 (95% CI, 0.855-0.974), respectively. The AUCs of nomogram constructed by the features fusion in combination with clinical baseline data were 0.998 (95% CI, 0.996–0.999) and 0.946 (95% CI, 0.906–0.987) in the training cohort and test cohort, respectively. The Delong test showed that the differences between the features fusion model and the nomogram in the training cohort and the test cohort were not statistically significant (P values were 0.794 and 0.668, respectively), and the differences in the other prediction models in the training cohort and the test cohort were statistically significant (P

BackgroundThe role of age in metastatic disease, including breast cancer, remains obscure. This study was conducted to determine the role of age in patients with de novo metastatic breast cancer.MethodsBreast cancer patients diagnosed with distant metastases between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results database. Comparisons were performed between young (aged ≤ 40 years), middle-aged (41–60 years), older (61–80 years), and the oldest old (> 80 years) patients. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazard models. Survival analysis was performed by the Kaplan–Meier method.ResultsThis study included 24155 (4.4% of all patients) de novo metastatic breast cancer patients. The number of young, middle-aged, older, and the oldest old patients were 195 (8.3%), 9397 (38.9%), 10224 (42.3%), and 2539 (10.5%), respectively. The 5-year OS rate was highest in the young (42.1%), followed by middle-aged (34.8%), older (28.3%), and the oldest old patients (11.8%). Multivariable Cox regression analysis showed that middle-aged (aHR, 1.18; 95% CI, 1.10–1.27), older (aHR, 1.42; 95% CI, 1.32–1.52), and the oldest old patients (aHR, 2.15; 95% CI, 1.98–2.33) had worse OS than young patients. Consistently, middle-aged (aHR, 1.16; 95% CI, 1.08–1.25), older (aHR, 1.32; 95% CI, 1.23–1.43), and the oldest old patients (aHR, 1.86; 95% CI, 1.71–2.03) had worse BCSS than young patients.ConclusionThis study provided clear evidence that de novo metastatic breast cancer had an age-specific pattern. Age was an independent risk factor for mortality in patients with de novo metastatic breast cancer.

Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world's swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan dose-dependently inhibited a PEDV infection at 24 h post-infection (EC50 value = 0.67 μM). We found that Fan mainly affected the PEDV replication phase but also inhibited PEDV at the attachment and internalization stages of the viral life cycle. Mechanistically, Fan blocked the autophagic flux in PEDV-infected cells by regulating the expression of autophagy-related proteins and changing PEDV virus particles. In summary, Fan inhibits PEDV infection by blocking the autophagic flux in cells. Our findings will help develop new strategies to prevent and treat PEDV infection.

The delta-1-pyrroline-5-carboxylate synthetase (P5CS) gene exercises a protective function in stressed plants. However, the relationship between proline accumulation caused by P5CS and abiotic stress tolerance in plants is not always clear, as P5CS overexpression has been reported to repress plant growth under normal conditions in several reports. We re-evaluated the role of P5CS in drought-tolerant rice breeding by expressing the AtP5CS1 and feedback-inhibition-removed AtP5CS1 (AtP5CS1F128A) genes under the regulation of an ABA-inducible promoter to avoid the potential side effects of P5CS overexpression under normal conditions. ABA-inducible AtP5CS1 and AtP5CS1F128A increased seedling growth in a nutrient solution (under osmotic stress) and grain yield in pot plants. However, the evidently deleterious effects of AtP5CS1 on grain quality, tiller number, and grain yield in the field indicated the unsuitability of P5CS for drought-tolerance breeding.

Abstract Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

Ultraviolet disinfection is an important method for controlling the large-scale outbreaks of diseases in aquaculture. As a novel and promising light source, ultraviolet light-emitting diode (UV-LED) has the advantages of safety, high efficiency and no environmental pollution risks. However, it remains unclear whether UV-LEDs can replace traditional UV light sources for aquaculture water treatment processes. Present study aimed to investigate the efficacy of UVC-LEDs (265 nm) on pathogenic bacteria, specifically Aeromonas salmonicida and Escherichia coli. The effects of UVC-LED dose, light conditions, and temperature on bacterial reactivation were also investigated. The results showed that exposure to UVC-LED effectively inactivated both types of bacteria. To achieve 4.5-log inactivation of A. salmonicida and E. coli, 24 mJ/cm2 and 28 mJ/cm2 UVC-LED irradiation were required, and the inactivation rate increased with increasing UVC-LED fluence. Both A. salmonicida and E. coli were revived after UVC-LED disinfection, and photoreactivation was significantly higher than dark reactivation. Bacterial reactivation rate due to high-dose UVC-LED treatment was significantly lower than that of low-dose. After 72 h of reactivation, photoreactivation and dark reactivation rates were 1 ± 0.4% and 2.2 ± 0.2%for A. salmonicida, and 0.02% and 0% for E. coli, respectively. Besides, the photoreactivation rates for the two bacteria exhibited different correlations with temperature. The highest photoreactivation rate for A. salmonicida was 68.7 ± 4% at 20°C, while the highest photoreactivation rate for E. coli was 53.98 ± 2.9% at 15°C for 48 h. This study reveals the rapid and efficient inactivation of bacteria by UVC-LED, and elucidates the mechanism and influencing factors for inactivation and reactivation by UVC-LED. The study also highlights that adequate UVC-LED irradiation and avoidance of visible light after UVC-LED disinfection can effectively inhibit bacterial reactivation. Our findings form a reference for the design and operation of UV disinfection in aquaculture.

Porcine epidemic diarrhea virus (PEDV) is a deadly pathogen infecting pig herds, and has caused significant economic losses around the world. Vaccination remains the most effective way of keeping the PEDV epidemic under control. Previous studies have shown that the host metabolism has a significant impact on viral replication. In this study, we have demonstrated that two substrates of metabolic pathway, glucose and glutamine, play a key role in PEDV replication. Interestingly, the boosting effect of these compounds toward viral replication appeared to be dose-independent. Furthermore, we found that lactate, which is a downstream metabolite, promotes PEDV replication, even when added in excess to the cell culture medium. Moreover, the role of lactate in promoting PEDV was independent of the genotype of PEDV and the multiplicity of infection (MOI). Our findings suggest that lactate is a promising candidate for use as a cell culture additive for promoting PEDV replication. It could improve the efficiency of vaccine production and provide the basis for designing novel antiviral strategies.

Abstract Background Maize rough dwarf disease (MRDD), a widespread disease caused by four pathogenic viruses, severely reduces maize yield and grain quality. Resistance against MRDD is a complex trait that controlled by many quantitative trait loci (QTL) and easily influenced by environmental conditions. So far, many studies have reported numbers of resistant QTL, however, only one QTL have been cloned, so it is especially important to map and clone more genes that confer resistance to MRDD. Results In the study, a major quantitative trait locus (QTL) qMrdd2, which confers resistance to MRDD, was identified and fine mapped. qMrdd2, located on chromosome 2, was consistently identified in a 15-Mb interval between the simple sequence repeat (SSR) markers D184 and D1600 by using a recombinant inbred line (RIL) population derived from a cross between resistant (“80007”) and susceptible (“80044”) inbred lines. Using a recombinant-derived progeny test strategy, qMrdd2 was delineated to an interval of 577 kb flanked by markers N31 and N42. We further demonstrated that qMrdd2 is an incompletely dominant resistance locus for MRDD that reduced the disease severity index by 20.4%. Conclusions A major resistance QTL (qMrdd2) have been identified and successfully refined into 577 kb region. This locus will be valuable for improving maize variety resistance to MRDD via marker-assisted selection (MAS).

Salmonella Typhimurium is an important food-borne pathogen. In this paper, multicellular behavior and associated characteristics of S. Typhimurium isolated from human and animal source food were studied. All the S. Typhimurium strains exhibiting multicellular behavior (100%) belonged to the ST34 type. In addition, most of the ST34-type multicellular behavior S. Typhimurium strains had a human origin (69.11%) and 98% of the ST34-type multicellular behavior strains exhibited strong biofilm formation capacity, which was much higher than that of non-multicellular behavior strains (7%, P

Drought stress is known to significantly limit crop growth and productivity. Lateral organ boundary domain (LBD) transcription factors—particularly class-I members—play essential roles in plant development and biotic stress. However, little information is available on class-II LBD genes related to abiotic stress in maize. Here, we cloned a maize class-II LBD transcription factor, ZmLBD5, and identified its function in drought stress. Transient expression, transactivation, and dimerization assays demonstrated that ZmLBD5 was localized in the nucleus, without transactivation, and could form a homodimer or heterodimer. Promoter analysis demonstrated that multiple drought-stress-related and ABA response cis-acting elements are present in the promoter region of ZmLBD5. Overexpression of ZmLBD5 in Arabidopsis promotes plant growth under normal conditions, and suppresses drought tolerance under drought conditions. Furthermore, the overexpression of ZmLBD5 increased the water loss rate, stomatal number, and stomatal apertures. DAB and NBT staining demonstrated that the reactive oxygen species (ROS) decreased in ZmLBD5-overexpressed Arabidopsis. A physiological index assay also revealed that SOD and POD activities in ZmLBD5-overexpressed Arabidopsis were higher than those in wild-type Arabidopsis. These results revealed the role of ZmLBD5 in drought stress by regulating ROS levels.

Supramolecular gels containing porphyrins and phthalocyanines motifs are attracting increased interests in a wide range of research areas. Based on the supramolecular gels systems, porphyrin or phthalocyanines can form assemblies with plentiful nanostructures, dynamic, and stimuli-responsive properties. And these π-conjugated molecular building blocks also afford supramolecular gels with many new features, depending on their photochemical and electrochemical characteristics. As one of the most characteristic models, the supramolecular chirality of these soft matters was investigated. Notably, the application of supramolecular gels containing porphyrins and phthalocyanines has been developed in the field of catalysis, molecular sensing, biological imaging, drug delivery and photodynamic therapy. And some photoelectric devices were also fabricated depending on the gelation of porphyrins or phthalocyanines. This paper presents an overview of the progress achieved in this issue along with some perspectives for further advances.

This study is to evaluate the efficacy of erythropoietin in treating sepsis-associated acute respiratory distress syndrome (ARDS). One hundred patients with sepsis-related ARDS were randomized into the placebo group and Erythropoietin (EPO) group. Patients in the placebo group received saline as placebo on the standard therapy, while the EPO group received recombinant human erythropoietin injections on the standard therapy. It was found that the heart rate and mean arterial pressure did not differ significantly between days 7 and 14 after treatment initiation (p > 0.05). The partial pressure of oxygen (PaO2) and oxygenation index levels measured on days 7 and 14 were significantly higher than the placebo group and partial pressure of carbon dioxide (PaCO2) was significantly lower than the placebo group (p < 0.05). Lung capacity and functional residual capacity (and FRC) increased significantly in tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and C-reactive protein (CRP) concentrations (p < 0.05). In the EPO group, the duration of mechanical ventilation was significantly shorter and the mortality rate was significantly reduced (Log-Rank test, χ² = 4.651, p = 0.031). The results confirm that EPO significantly improves lung function and blood gas parameters, reduces serum levels of inflammatory markers, and reduces the risk of death in sepsis-induced ARDS patients, highlighting the potential therapeutic role of EPO in the management of this disease. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the molecular markers indicative of early-stage hypothyroidism induced by treatment with iodine-131, in order to assist in further investigations of radio iodine-induced hypothyroidism. A total of 59 patients diagnosed with hyperthyroidism (male/female, 16/43; median age, 46.4 years) and 27 healthy subjects (male/female, 7/21; median age, 44.6 years) were included in the present study. All patients were treated with appropriate doses of iodine-131 and, three months following treatment, the patients were subdivided into two groups: A group with early-stage hypothyroidism symptoms, and a group with non-early-stage hypothyroidism, including euthyroid patients and patients remaining with hyperthyroidism. Tissue samples from the patients and healthy subjects were collected by fine needle biopsies, and the mRNA expression levels of B-cell lymphoma 2 (Bcl-2), nuclear factor (NF)-κB, Ku70, epidermal growth factor receptor (EGFR), early growth response 1 (Egr-1), TP53 and ataxia telangiectasia mutated were analyzed using reverse transcription-quantitative polymerase chain reaction prior to iodine-131 treatment. The association of the variation of target genes with susceptibility to early-stage hypothyroidism was analyzed. Compared with normal subjects, the mRNA expression levels of Ku70 (0.768, vs. 3.304, respectively; P<0.001) and EGFR (0.859, vs. 1.752, respectively; P<0.05) were significantly higher, whereas those of NF-κB (0.884, vs. 0.578, respectively; P<0.05) and Bcl-2 (1.235, vs. 0.834, respectively; P<0.05) were lower in the hyperthyroid patients. Following treatment with iodine-131, 30 of the 59 (50.8%) patients with hyperthyroidism were diagnosed with early-stage hypothyroidism, and in the early-stage hypothyroidism group, the mRNA expression levels of Bcl-2 were significantly decreased (P<0.05), whereas those of Egr-1 (P<0.05) were significantly increased, compared with the non-early-stage hypothyroidism group. The association between the changes in the expression levles of Bcl-2 and Egr-1 and susceptibility to early-stage hypothyroidism was supported by multivariate regression analysis. No significant changes in the expression levels of the other target genes were detected. The opposing changes in the mRNA expression levels of Bcl-2 and Egr-1 in patients with early-stage hypothyroidism indicates their potential as prognostic markers of early-stage hypothyroidism induced by iodine-131 treatment. [ABSTRACT FROM AUTHOR]

Iodine-131 is known to destroy residual thyroid tissue following surgical resection of differentiated thyroid carcinoma and is widely used to treat hyperthyroidism. However, the mechanism by which iodine-131 induces apoptosis and cell cycle arrest in the human thyrocyte cell line, Htori-3, remains to be elucidated. In the present study, the cytotoxic effect of iodine-131 on the HTori-3 cell line and the underlying mechanism of iodine-131-induced cell apoptosis were investigated. Cell viability was analyzed using an MTT assay, while cell apoptosis and cell cycle arrest were determined using flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to determine the changes in the expression levels of p53, B-cell lymphoma 2 (Bcl-2), Fas and growth arrest and DNA damage-inducible 45 (GADD45), following iodine-131 treatment. The results demonstrated that iodine-131 may inhibit HTori-3 cell growth via cell apoptosis and G2/M phase arrest in a time- and dose-dependent manner. The iodine-131 dose required for 50% growth inhibition of HTori-3 cell viability 48 h after treatment was 27.75±2.22 MBq/ml. Upregulation of Fas and downregulation of Bcl-2 expression levels were observed following iodine-131 treatment. The results of RT-qPCR revealed an increase in the GADD45 mRNA expression following HTori-3 cell exposure to iodine-131. Notably, the mRNA and protein expression levels of p53 were not altered following iodine-131 treatment. In conclusion, iodine-131 may induce apoptosis in HTori-3 cells by downregulating the expression of Bcl-2 and upregulating the expression of Fas. In addition, iodine-131 may upregulate GADD45 mRNA expression in HTori-3 cells, resulting in G2/M phase arrest in a p53-independent pathway. [ABSTRACT FROM AUTHOR]