Systematic impacts of fluoride exposure on the metabolomics of rats.

Fluoride is widely present in the environment. Excessive fluoride exposure leads to fluorosis, which has become a global public health problem and will cause damage to various organs and tissues. Only a few studies focus on serum metabolomics, and there is still a lack of systematic metabolomics associated with fluorosis within the main organs. Therefore, in the current study, a non-targeted metabolomics method using gas chromatography-mass spectrometry (GC-MS) was used to research the effects of fluoride exposure on metabolites in different organs, to uncover potential biomarkers and study whether the affected metabolic pathways are related to the mechanism of fluorosis. Male Sprague-Dawley rats were randomly divided into two groups: a control group and a fluoride exposure group. GC-MS technology was used to identify metabolites. Multivariate statistical analysis identified 16, 24, 20, 20, 24, 13, 7, and 13 differential metabolites in the serum, liver, kidney, heart, hippocampus, cortex, kidney fat, and brown fat, respectively, in the two groups of rats. Fifteen metabolic pathways were affected, involving toxic mechanisms such as oxidative stress, mitochondrial damage, inflammation, and fatty acid, amino acid and energy metabolism disorders. This study provides a new perspective on the understanding of the mechanism of toxicity associated with sodium fluoride, contributing to the prevention and treatment of fluorosis.

A China-Based Cost-Effectiveness Analysis of Novel Oral Anticoagulants versus Warfarin in Patients with Left Ventricular Thrombosis.

Purpose: This study aims to conduct a comprehensive cost-effectiveness comparison between novel oral anticoagulants (NOACs) and warfarin in Chinese patients with left ventricular thrombosis (LVT). By incorporating the impact of volume-based procurement (VBP) policy for pharmaceuticals in China, this analysis intends to provide crucial insights for informed healthcare decision-making. Patients and Methods: A Markov model was employed to simulate the disease progression of LVT over a 54-week time horizon, using weekly cycles and six mutually exclusive health states. The model incorporated transition probabilities between health states calculated based on clinical trial data and literature sources. Various cost and utility parameters were also included. Additionally, a series of sensitivity analyses were conducted to address parameter variations and associated uncertainties. Results: The study finding suggest that from the perspective of Chinese healthcare, the majority of brand-name drug (BND) NOACs generally lack cost-effectiveness when compared to warfarin. However, when considered the VBP policy, NOACs, particularly rivaroxaban, prove to be more cost-effective than warfarin. Rivaroxaban provided an additional 0.0304 quality-adjusted life years (QALYs) per patient and reduced overall medical costs by 9095.73 CNY, resulting in an incremental cost-effectiveness ratio (ICER) of -298,786.20 CNY/QALY. Sensitivity analysis indicated a 78.4% probability of any NOACs being more cost-effective compared to warfarin. However, specifically considering NOACs under the VBP policy, the likelihood of them being more cost-effective approached 90%. Conclusion: Taking into account Chinese pharmaceutical procurement policies, the findings highlight the superior efficacy of NOACs, especially rivaroxaban, in enhancing both the quality of life and economic benefits for Chinese LVT patients. NOACs present a more cost-effective treatment option, improving patient quality of life and healthcare cost efficiency compared to warfarin.

Machine Learning Predicts the Oxidative Stress Subtypes Provide an Innovative Insight into Colorectal Cancer.

So far, it has been reached the academic consensus that the molecular subtypes are via genomic heterogeneity and immune infiltration patterns. Considering that oxidative stress (OS) is involved in tumorigenesis and prognosis prediction, we propose an innovative classification of colorectal cancer- (CRC-) OS subtypes. We obtain three datasets from The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) online databases. 1399 OS-related genes were selected from the GeneCards database. We remove the batch effect before conducting differentially expressed genes (DEGs) analyses between normal and tumor samples. Nonnegative matrix factorization (NMF) was used to perform an unsupervised cluster. Lasso regression and Cox regression were used to construct the signature model. DEGs, robust rank aggregation, and protein-protein interaction networks were used to select hub genes, and then use hub genes to predict OS subtypes by random forest algorithms. NMF identifies two OS-related subtypes of CRC patients. Eight OS-related gene signatures were built to predict the outcome of patients, based on the DEGs between two subtypes. A total of 61 DEGs overlap each dataset, and the RRA analysis shows that 17 genes are important in these three datasets, and 15 genes are shared genes between the two methods. PPI network suggests that five hub genes are confirmed, they are SPP1, SERPINE1, CAV1, PDGFRB, and PLAU. These five hub genes could predict the OS-related subtype of CRC accurately with AUC equal to 0.771. In our study, we identify two OS-related subtypes, which will provide an innovative insight into colorectal cancer.

Involvement of LARP7 in Activation of SIRT1 to Inhibit NF-κB Signaling Protects Microglia from Acrylamide-Induced Neuroinflammation.

Acrylamide (AM) is a potent neurotoxin and carcinogen that is mainly formed by the Maillard reaction of asparagine with starch at high temperatures. However, the toxicity mechanism underlying AM has not been investigated from a proteomic perspective, and the regulation of protein expression by AM remains poorly understood. This research was the first to utilize proteomics to explore the mechanism of AM exposure-induced neuroinflammation. Target proteins were obtained by differential protein analysis, functional annotation, and enrichment analysis of proteomics. Then, molecular biology methods, including Western blot, qPCR, and immunofluorescence, were used to verify the results and explore possible mechanisms. We identified 100 key differential metabolites by proteomic analysis, which was involved in the occurrence of various biological functions. Among them, the KEGG pathway enrichment analysis showed that the differential proteins were enriched in the P53 pathway, sulfur metabolism pathway, and ferroptosis. Finally, the differential target protein we locked was LARP7. Molecular biological verification found that AM exposure inhibited the expression of LARP7 and induced the burst of inflammation, while SRT1720 agonist treatment showed no effect on LARP7, but significant changes in inflammatory factors and NF-κB. Taken together, these findings suggested that AM may activate NF-κB to induce neuroinflammation by inhibiting the LARP7-SIRT1 pathway. And our study provided a direction for AM-induced neurotoxicity through proteomics and multiple biological analysis methods.

Effect of Organic Substances on Nutrients Recovery by Struvite Electrochemical Precipitation from Synthetic Anaerobically Treated Swine Wastewater.

Anaerobically treated swine wastewater contains large amounts of orthophosphate phosphorus, ammonium nitrogen and organic substances with potential nutrients recovery via struvite electrochemical precipitation post-treatment. Lab-scale batch experiments were systematically conducted in this study to investigate the effects of initial pH, current density, organic substances upon nutrients removal, and precipitates quality (characterized by X-ray diffraction, scanning electron microscopy and element analysis via acid dissolution method) during the struvite electrochemical precipitation process. The optimal conditions for the initial pH of 7.0 and current density of 4 mA/cm2 favoured nutrients removal and precipitates quality (struvite purity of up to 94.2%) in the absence of organic substances. By contrast, a more adverse effect on nutrients removal, morphology and purity of precipitates was found by humic acid than by sodium alginate and bovine albumin in the individual presence of organic substances. Low concentration combination of bovine albumin, sodium alginate, and humic acid showed antagonistic inhibition effects, whereas a high concentration combination showed the accelerating inhibition effects. Initial pH adjustment from 7 to 8 could effectively mitigate the adverse effects on struvite electrochemical precipitation under high concentration combined with organic substances (500 mg/L bovine albumin, 500 mg/L sodium alginate, and 1500 mg/L humic acid); this may help improve struvite electrochemical precipitation technology in practical application for nutrients recovery from anaerobically treated swine wastewater.

Comprehensive analysis of metabolic changes in rats exposed to acrylamide.

Acrylamide (ACR) is a widely used environmentally hazardous compound that is known to be neurotoxic, genotoxic, carcinogenic, and reproductive toxicity. It is widely present in soil, water, agents used in chemical industries, and food. It can be distributed to all organs and tissues, and can cause damage to various human systems and those of other animals. Previous metabolomics studies have mainly focused on metabolites in serum and urine, but have lacked comprehensive analysis of major organs and tissues. In the current study, a gas chromatography-massspectrometry method was used to investigate mechanisms underlying organ toxicity, in an effort to identify potentially sensitive biomarkers in the main target tissues of rats after ACR exposure. Male Sprague-Dawley rats were assigned to two groups; a control group and a group treated with 20 mg kg-1 ACR intragastrically for 6 weeks. Metabolite changes in the two groups were statistically analyzed. The respective numbers of altered metabolites in the hippocampus, cortex, kidney, serum, heart, liver, and kidney fat were 21, 21, 17, 5, 15, 14, and 6. There were 14 metabolic pathways related to amino acid, fatty acid, purine, and energy metabolism, revealing that the toxic mechanism of ACR may involve oxidative stress, inflammation, and amino acid metabolism and energy disorders.

Development and Validation of a Preoperative Magnetic Resonance Imaging Radiomics-Based Signature to Predict Axillary Lymph Node Metastasis and Disease-Free Survival in Patients With Early-Stage Breast Cancer.

Importance: Axillary lymph node metastasis (ALNM) status, typically estimated using an invasive procedure with a high false-negative rate, strongly affects the prognosis of recurrence in breast cancer. However, preoperative noninvasive tools to accurately predict ALNM status and disease-free survival (DFS) are lacking. Objective: To develop and validate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of ALNM and to assess individual DFS in patients with early-stage breast cancer. Design, Setting, and Participants: This retrospective prognostic study included patients with histologically confirmed early-stage breast cancer diagnosed at 4 hospitals in China from July 3, 2007, to September 21, 2019, randomly divided (7:3) into development and vaidation cohorts. All patients underwent preoperative MRI scans, were treated with surgery and sentinel lymph node biopsy or ALN dissection, and were pathologically examined to determine the ALNM status. Data analysis was conducted from February 15, 2019, to March 20, 2020. Exposure: Clinical and DCE-MRI radiomic signatures. Main Outcomes and Measures: The primary end points were ALNM and DFS. Results: This study included 1214 women (median [IQR] age, 47 [42-55] years), split into development (849 [69.9%]) and validation (365 [30.1%]) cohorts. The radiomic signature identified ALNM in the development and validation cohorts with areas under the curve (AUCs) of 0.88 and 0.85, respectively, and the clinical-radiomic nomogram accurately predicted ALNM in the development and validation cohorts (AUC, 0.92 and 0.90, respectively) based on a least absolute shrinkage and selection operator (LASSO)-logistic regression model. The radiomic signature predicted 3-year DFS in the development and validation cohorts (AUC, 0.81 and 0.73, respectively), and the clinical-radiomic nomogram could discriminate high-risk from low-risk patients in the development cohort (hazard ratio [HR], 0.04; 95% CI, 0.01-0.11; P < .001) and the validation cohort (HR, 0.04; 95% CI, 0.004-0.32; P < .001) based on a random forest-Cox regression model. The clinical-radiomic nomogram was associated with 3-year DFS in the development and validation cohorts (AUC, 0.89 and 0.90, respectively). The decision curve analysis demonstrated that the clinical-radiomic nomogram displayed better clinical predictive usefulness than the clinical or radiomic signature alone. Conclusions and Relevance: This study described the application of MRI-based machine learning in patients with breast cancer, presenting novel individualized clinical decision nomograms that could be used to predict ALNM status and DFS. The clinical-radiomic nomograms were useful in clinical decision-making associated with personalized selection of surgical interventions and therapeutic regimens for patients with early-stage breast cancer.

[Difference of P content in different area substrate of constructed wetland].

Adsorption of substrate is the main removal mechanisms of phosphorus in constructed wetland. It is easily impacted by various environmental factors existing in the wetland bed. The contents of substrate TP and the main inorganic P in different areas of both horizontal sub-surface flow constructed wetland with plant and one without plant were measured after treating wastewater five months. Different areas of the wetland with plant differed greatly in the substrate TP. Rhizosphere substrate in front area had the highest TP content and achieved 0.75 g x kg(-1), and the TP content of non-rhizosphere substrate in back area was only 0.21 g x kg(-1). The TP content of substrate in different areas of the wetland without plant had a little variety and ranged only between 0.21 and 0.27 g x kg(-1). Averagely, the substrate TP content in the wetland with plant was higher than the one in the wetland without plant. The phosphorous with Fe-bound (Fe-P), Al-bound (Al-P), and Ca-bound (Ca-P) were main inorganic phosphorous existing in the substrate in both wetlands, their contents in different areas substrate all increased, compared with the one before experiment. Fe-P and Al-P in different substrates in both wetlands had a similar variety. Their content between rhizosphere and intermediate substrate of front area in the wetland with plant and other area substrate in both wetlands differed greatly because the former increased greatly. Compared with Fe-P and Al-P, the variety of Ca-P in different substrates in both wetlands was low. But the content of Ca-P in rhizosphere substrate in wetland with plant was higher than other two parts respectively in front and back areas. Obviously, the plant root had an impact on the phosphorous content of substrate in constructed wetland. For TP, Fe-P, Al-P, Ca-P and loosely sorbed phosphorous in substrate, it increased with distance of the root.

[Characterization of Cr (VI) removal and total Cr equilibrium adsorption by sulfate reducing granular sludge in stimulant wastewater].

Sulfate reducing granular sludge (SRGS) cultivated in small scale EGSB reactor was used for Cr (VI) removing. Characterization of Cr (VI) removal and total Cr equilibrium adsorption was studied, and the adsorption isotherm was fitted. Results showed that removal of Cr (VI) was in connection with the structure and chemical composition of SRGS and several environmental factors. The Cr (VI) removal rate increased with the dosage of granular sludge; the increasing of oscillation speed and temperature could enhance Cr (VI) removal and total Cr adsorption, but while the oscillation speed reached 150 r x min(-1) or the temperature came to 40 degrees C, the physical structure of granular sludge would be affected and the granular sludge discrete, and total Cr equilibrium adsorption decreased; lower pH value caused higher Cr (VI) removal rate, however the sulfate on the surface of granular sludge was affected by lower pH value easily and would translate into H2S, then total Cr adsorption rate decreased. Cr (VI) removal would be influenced by physical, chemical and biological factors, and the process included reduction and adsorption mainly. The maximum adsorption of total Cr by granular sludge was 6.84 mg x g(-1), and the total Cr adsorbing process fitted in with Langmuir adsorption isotherm.