Comprehensive toxicological, metabolomic, and transcriptomic analysis of the biodegradation and adaptation mechanism by Achromobacter xylosoxidans SL-6 to diuron.

Biodegradation was considered a promising and environmentally friendly method for treating environmental pollution caused by diuron. However, the mechanisms of biodegradation of diuron required further research. In this study, the degradation process of diuron by Achromobacter xylosoxidans SL-6 was systematically investigated. The results suggested that the antioxidant system of strain SL-6 was activated by adding diuron, thereby alleviating their oxidative stress response. In addition, degradation product analysis showed that diuron in strain SL-6 was mainly degraded by urea bridge cleavage, dehalogenation, deamination, and ring opening, and finally cis, cis-muconic acid was generated. The combined analysis of metabolomics and transcriptomics revealed the biodegradation and adaptation mechanism of strain SL-6 to diuron. Metabolomics analysis showed that after the strain SL-6 was exposed to diuron, metabolic pathways such as tricarboxylic acid cycle (cis, cis-muconic acid), glutathione metabolism (oxidized glutathione), and urea cycle (arginine) were reprogrammed in the cells. Furthermore, diuron could induce the production of membrane transport proteins in strain SL-6 cells and overexpress antioxidant enzyme genes, finally ultimately promoting the up-regulation of genes encoding amide hydrolases and dioxygenases, which was revealed by transcriptomics studies. This work enriched the biodegradation mechanism of phenylurea herbicides and provided guidance for the removal of diuron residues in the environment and promoting agriculture sustainable development.

Retrospective study of the influence of hypothyroidism on liver function before radioiodine therapy in China: a comparison analysis based on patients with differentiated thyroid cancer.

PURPOSE: The aim of the present study is to investigate the risk factors for hepatic dysfunction before radioiodine therapy in patients with differentiated thyroid cancer (DTC). METHODS: 996 patients (314 men, 682 women; age of 45.07±12.98 years) with postoperative DTC were recruited and divided into two groups including patients with and without hepatic dysfunction. The changes in baseline data and traced liver function levels, together with other metabolic profiles, were compared between the two groups. RESULT: Overall, 31.6% of patients had hepatic dysfunction. Higher aspartate aminotransferase and/or alanine aminotransferase was the most common abnormality (the prevalence rate was 47.5%). The percentages of mild and moderate hepatic dysfunction were 80.0% and 20.0%, respectively. Univariate analyses demonstrated that the most prominent risk factors for hepatic dysfunction (OR=0.324-3.171, p<0.01) were male sex with levothyroxine discontinuation and free triiodothyronine <2.01 pmol/L, free thyroxine (FT4) <4.78 pmol/L, thyroid-stimulating hormone >78.195 µIU/mL, total cholesterol >5.17 mmol/L, triglycerides (TG) >1.71 mmol/L and more than 21 days of thyroid hormone withdrawal. Multivariate analyses demonstrated that for men, FT4 <3.80 pmol/L and TG ≥1.28 mmol/L were the most prominent risk factors. CONCLUSIONS: Patients with minor hepatic dysfunction and ortholiposis are more likely to recover to normal liver function. Patients with moderate hepatic dysfunction should be treated with hepatoprotective drugs. For men, FT4 and TG levels tended to be associated with hepatic dysfunction, and the prognosis of hepatic dysfunction was closely related to the TG level.

Bone metastases in newly diagnosed patients with thyroid cancer: A large population-based cohort study.

Background: Population-based estimates of the incidence and prognosis of bone metastases (BM) stratified by histologic subtype at diagnosis of thyroid cancer are limited. Methods: Using multivariable logistic and Cox regression analyses, we identified risk factors for BM and investigated the prognostic survival of BM patients between 2010 and 2015 via the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among 64,083 eligible patients, a total of 347 patients with BM at the time of diagnosis were identified, representing 0.5% of the entire cohort but 32.4% of the subset with metastases. BM incidence was highest (11.6%) in anaplastic thyroid cancer (ATC), which, nevertheless, was highest (61.5%) in follicular thyroid cancer (FTC) among the subset with metastases. The median overall survival among BM patients was 40.0 months, and 1-, 3-, and 5-year survival rates were 65.2%, 51.3%, and 38.7%, respectively. Compared with papillary thyroid cancer (PTC), FTC (aOR, 6.33; 95% CI, 4.72-8.48), medullary thyroid cancer (MTC) (aOR, 6.04, 95% CI, 4.09-8.92), and ATC (aOR, 6.21; 95% CI, 4.20-9.18) significantly increased the risk of developing BM. However, only ATC (aHR, 6.07; 95% CI, 3.83-9.60) was independently associated with worse survival in multivariable analysis. Additionally, patients with BM alone (56.5%) displayed the longest median survival (66.0 months), compared with those complicated with one extraskeletal metastatic site (lung, brain, or liver) (35.2%; 14.0 months) and two or three sites (8.3%; 6.0 months). The former 5-year overall survival rate was 52.6%, which, however, drastically declined to 23.0% in patients with one extraskeletal metastatic site and 9.1% with two or three sites. Conclusion: Closer bone surveillance should be required for patients with FTC, MTC, and ATC, and extraskeletal metastases at initial diagnosis frequently predict a poorer prognosis.

Physiological and biochemical effects of Ti3AlC2 nanosheets on rice (Oryza sativa L.).

MAX phase materials are a new type of nanomaterial with wide applications, but the potential effects of MAX phase materials on plants have not been reported. Herein, we selected Ti3AlC2 nanosheets as a typical MAX phase material to investigate its potential impacts on rice (Oryza sativa L.) at 0-1000 µg·mL-1. The foliar application of Ti3AlC2 at 100 and 1000 µg·mL-1 inhibited the growth of rice seedlings by producing excess reactive oxygen species (ROS). Furthermore, foliar spraying of Ti3AlC2 at 100 µg·mL-1 decreased the stomatal aperture (78.6%) and increased the number of trichomes (100%). These responses demonstrated that the application of Ti3AlC2 could interfere with the immune system of plants by changing the structure and function of leaves, disturbing the activities of antioxidant enzymes. According to the above results, we concluded that the toxicity of Ti3AlC2 nanosheets on plants was mainly caused by the release of titanium ions. This study provides a valuable reference for understanding the impact of MAX phase materials on plants.

Multifunctional molybdenum disulfide-copper nanocomposite that enhances the antibacterial activity, promotes rice growth and induces rice resistance.

Molybdenum disulfide sheets loaded with copper nanoparticles (MoS2-CuNPs) was prepared and its antibacterial activity against phytopathogen Xanthomonas oryzae pv. oryzae (Xoo) was investigated in vitro and in vivo for the first time. In a 2 h co-incubation, MoS2-CuNPs exhibited 19.2 times higher antibacterial activity against Xoo cells than a commercial copper bactericide (Kocide 3000). In the detached leaf experiment, the disease severity decreased from 86.25 % to 7.5 % in the MoS2-CuNPs treated rice leaves. The results further demonstrated that foliar application of MoS2-CuNPs could form a protective film and increase the density of trichome on the surface of rice leaves, finally prevent the infection of Xoo cells. This was probably due to the synergistic effect of MoS2-CuNPs. Additionally, foliar application of MoS2-CuNPs (4-32 µg/mL) increased obviously the content of Mo and chlorophyll (up 30.85 %), and then improved the growth of rice seedlings. Furthermore, the obtained MoS2-CuNPs could activate the activities of the antioxidant enzymes in rice, indicating higher resistance of rice under abiotic/biotic stresses. The multifunctional MoS2-CuNPs with superior antibacterial activity provided a promising alternative to the traditional antibacterial agents and had great potential in plant protection.

Downregulation of miR-146b-3p Inhibits Proliferation and Migration and Modulates the Expression and Location of Sodium/Iodide Symporter in Dedifferentiated Thyroid Cancer by Potentially Targeting MUC20.

The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (131I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of 131I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and in vitro functional experiments were conducted. FLG, FRG1, MUC6, MUC20, and PRUNE2 were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of miR-146b-3p target MUC20 was explored. The expression levels of miR-146b-3p and MUC20 were significantly increased, and the inhibition of miR-146b-3p expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, miR-146b-3p potentially targets MUC20 participation in the formation of DTC dedifferentiation, resulting in resistance to 131I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. miR-146b-3p may be a potentially therapeutic target for the reapplication of 131I therapy in dedifferentiated thyroid cancer patients.