Progressive Research in the Molecular Mechanisms of Chronic Fluorosis

Long-term excessive intake of fluoride (F) leads to chronic fluorosis, resulting in dental fluorosis and skeletal fluorosis. Chronic exposure to high doses of fluoride can also cause damage to soft tissues, especially when it passes through the blood-brain, blood-testis, and blood-placenta barrier, causing damage to the corresponding tissues. Fluorosis has become a public health problem in some countries or regions around the world. Understanding the pathogenesis of fluorosis is very important. Although the exact mechanism of fluorosis has not been fully elucidated, various mechanisms of fluoride-induced toxicity have been proposed. In this chapter, we will introduce the research progress of the mechanism of fluorosis, focusing on dental fluorosis, skeletal fluorosis, nervous and reproductive system toxicity, and influential factors related to fluoride toxicity (i.e., genetic background, co-exposure with other element). In addition, the application of proteomics and metabolomics in the study of the pathogenesis of fluorosis is also introduced. Currently, there is still no specific treatment for fluorosis. However, since fluorosis is caused by excessive intake of fluoride, avoiding excessive fluoride intake is the critical measure to prevent the disease. In endemic regions, health education and supplement diet with vitamins C, D and E, and calcium and antioxidant compounds are important

Proteomics Study of Peripheral Blood Mononuclear Cells (PBMCs) in Autistic Children

Autism is one of the most common neurological developmental disorder associated with social isolation and restricted interests in children. The etiology of this disorder is still unknown. There is neither any confirmed laboratory test nor any effective therapeutic strategy to diagnose or cure it. To search for biomarkers for early detection and exploration of the disease mechanisms, here, we investigated the protein expression signatures of peripheral blood mononuclear cells (PBMCs) in autistic children compared with healthy controls by using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach. The results showed a total of 41 proteins as differentially expressed in autistic group as compared to control. These proteins are found associated with metabolic pathways, endoplasmic reticulum (ER) stress and protein folding, endocytosis, immune and inflammatory response, plasma lipoprotein particle organization, and cell adhesion. Among these, 17 proteins (13 up-regulated and four down-regulated) are found to be linked with mitochondria. Eight proteins including three already reported proteins in our previous studies were selected to be verified. Five already reported autism associated pro-inflammatory cytokines [interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α)] were detected in plasma by enzyme-linked immunosorbent assay (ELISA) analysis. The results were consistent with proteomic results and reports from previous literature. These results proposed that PBMCs from autistic children might be activated, and ER stress, unfolded protein response (UPR), acute-phase response (APR), inflammatory response, and endocytosis may be involved in autism occurrence. These reported proteins may serve as potential biomarkers for early diagnosis of autism. More specifically, simultaneous detection of three proteins [complement C3 (C3), calreticulin (CALR), and SERPINA1] in the plasma and PBMCs could increase the authenticity of detection

Proteomics insights into the basis of interspecific facilitation for maize (Zea mays) in faba bean (Vicia faba)/maize intercropping

Faba bean/maize intercropping significantly promotes maize productivity in phosphorus-deficient soils. This has been attributed to the below-ground interactions including rhizosphere effects and spatial effects. Nevertheless, the molecular mechanisms underlying these interactions have been scarcely investigated. Here, three types of pots were used to distinguish the influences of rhizosphere effects vs. spatial effects. Phosphorus and nitrogen uptake of shoots, biomass, total root length, and root classification were evaluated between the three treatments. Quantitative RT-PCR and proteomics analyses were conducted to investigate the putative components in the molecular basis of these interactions. Quantitative RT-PCR results indicated that rhizosphere effects promoted maize phosphorus status at molecular levels. 66 differentially accumulated protein spots were successfully identified through proteomics analyses. Most of the protein species were found to be involved in phosphorus, nitrogen, and allelochemical metabolism, signal transduction, or stress resistance. The results suggest that rhizosphere effects promoted phosphorus and nitrogen assimilation in maize roots and thus enhanced maize growth and nutrient uptake. The reprogramming of proteome profiles suggests that rhizosphere effects can also enhance maize tolerance through regulating the metabolism of allelochemicals and eliciting systemic acquired resistance via the stimulation of a mitogen-activated protein kinase signal pathway. Biological significance The results obtained contribute to a comprehensive understanding of the response of maize to the changes of rhizosphere condition influenced by the below-ground interactions in faba bean/maize intercropping at molecular levels. The identified protein species involved in nutrient metabolisms and stress resistance reveal the molecular basis underlying the major advantages of effective nutrient utilization and higher stress tolerance in legume/cereal intercropping systems. This work provides essential new insights into the putative components in the molecular basis of interspecific facilitation for maize in faba bean/maize intercropping. (C) 2014 Elsevier B.V. All rights reserved

Self-supervised molecular pretraining strategy for low-resource reaction prediction scenarios

In the face of low-resource reaction training samples, we construct a chemical platform for addressing small-scale reaction prediction problem. By using a self-supervised pretraining strategy called MASS, the transformer model can absorb the chemical information about 1 billion molecules and then finetunes on small-scale reaction prediction, which is different from previous works that only rely on reaction samples. To demonstrate the broad applicability of our approach, we adopt three dif-ferent name reactions in our work. In the Baeyer-Villiger, Heck and Sharpless asymmetric epoxidation reaction prediction tasks, the average accuracies increase by 5.7%, 10.8%, 4.8% respectively, marking an important step to low-resource reaction prediction

Characterization of Porous Titanium-Hydroxyapatite Composite Biological Coating on Polyetheretherketone (PEEK) by Vacuum Plasma Spraying

Titanium powders and hydroxyapatite powders were used to fabricate the titanium and hydroxyapatite composite coating (Ti/Ti/HA) on the Polyetheretherketone (PEEK) by vacuum plasma spraying (VPS). The phase composition and morphology of the Ti/Ti/HA coating were analyzed by XRD, SEM, industrial CT, and three-dimensional contour profiler (DEKTAK XT). The results showed that the phase composition of the Ti/Ti/HA coating was dominated by the HA phase and a small amount of the Ti phase. The Ti/Ti/HA composite coating presented an obvious three-layer structure with different roughness and porosity. The bottom was Ti coating with a porosity less than 10%; the middle was porous Ti coating with a porosity of 35% ± 10%; the surface coating was HA coating with the crystallinity near 95%, a porosity of 32% ± 10%, a roughness Ra = 30 ± 10 μm. Moreover, the TG-DSC and ATR-FTIR results showed that VPS coating has no effect on thermochemical properties of PEEK material. The average bond strength of the composite coating was achieved 32 MPa

Depicting the Profile of METTL3-Mediated lncRNA m6A Modification Variants and Identified SNHG7 as a Prognostic Indicator of MNNG-Induced Gastric Cancer

As a representative example of an environmental chemical carcinogen, MNNG exposure is closely associated with the onset of gastric cancer (GC) where N6-methyladenosine (m6A) RNA methylation tends to be the critical epigenetic event. However, the effect of m6A modification on long non-coding RNAs (lncRNAs) in MNNG-induced GC onset is still unclear. To address the above issue, based on the Methylated RNA immunoprecipitation sequencing (MeRIP-seq) data of MNNG-induced malignant cells (MCs) and GC cells, we comprehensively analyzed the MNNG exposure-associated vital lncRNAs. MeRIP-seq analysis identified 1432 lncRNA transcripts in the MC cell, and 3520 lncRNA transcripts were found to be m6A modified in the GC cell, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that MNNG exposure could spark cellular localization change, which might be the critical cellular note variation for malignant transformation. We demonstrated that METTL3 is responsible for N6 methylation of lncRNAs and identified SNHG7 as a downstream target of METTL3. More importantly, we observed that SNHG7 was progressively up-regulated during gastric carcinogenesis by MNNG exposure. Finally, we investigated SNHG7 expression in different stages of GC malignancies and found that elevated SNHG7 expression correlated with advanced clinical features and poor prognosis in GC. In conclusion, our study found for the first time that METTL3 regulates the m6A methylation level of lncRNA SNHG7 and its expression in MNNG exposure-induced GC, suggesting that SNHG7 as a predictive biomarker or therapeutic target for GC

Promoter polymorphism in the serotonin transporter (5-HTT) gene is significantly associated with leukocyte telomere length in Han Chinese.

The serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR) plays an important role in modulating mood and behavior by regulating 5-HTT expression and thereby controlling the concentration of serotonin (5-HT) in brain synapses: The homozygous shorter allele (S/S) in 5-HTTLPR results in lower 5-HTT expression coupled with stronger psycho-pathological reactions to stressful experiences compared to the homozygous long (L/L) and heterozygous (S/L) alleles. Psychological insults and mood disorders have been shown to cause accelerated telomere shortening, a marker of biological aging, however, it is currently unclear whether the allelic variants of 5-HTTLPR affect telomere length (TL) in the healthy population without mood disorders. In the present study, we determined the relationship between TL and the 5-HTTLPR variants in healthy Han Chinese. The 5-HTTLPR genotyping and leukocyte TL analysis of 280 young female Han Chinese freshmen showed a significantly shorter TL in 149 of them carrying the 5-HTTLPR S/S version compared to those (131) with the L/S or L/S plus L/L genotypes (mean ± SD, 0.533±0.241 for S/S vs 0.607±0.312 for L/S, P  =  0.034; or vs 0.604±0.313 for L/S plus L/L, P  =  0.038). Similar results were achieved in the other cohort including 220 adult healthy individuals of different age, gender and profession (0.691±0.168 for S/S vs 0.729±0.211 for L/S, P  =  0.046, or vs 0.725±0.213 for L/S plus L/L, P  =  0.039). Taken together, shorter leukocyte TL is significantly associated with the 5-HTTLPR S/S allelic variant, which may be implicated in psychological stress-related health problems