Impacts of complex electromagnetic radiation and low-frequency noise exposure conditions on the cognitive function of operators.

Background: Both electromagnetic radiation (EMR) and low-frequency noise (LFN) are widespread and influential environmental factors, and operators are inevitably exposed to both EMR and LFN within a complex exposure environment. The potential adverse effects of such exposure on human health must be considered seriously. This study aimed to investigate the effects of EMR and LFN on cognitive function as well as their interaction effect, which remain unclear. Methods: Sixty young male college students were randomly grouped and experiments were conducted with a 2 × 2 factorial design in a shielded chamber. Mental workload (MWL) levels of the study subjects were measured and assessed using the NASA-task load index (TLX) subjective scale, an n-back task paradigm, and the functional near-infrared spectroscopy (fNIRS) imaging technique. Results: For the 3-back task, the NASA-TLX subjective scale revealed a statistically significant main effect of LFN intensity, which enhanced the subjects' MWL level (F = 8.716, p < 0.01). Behavioral performance revealed that EMR intensity (430.1357 MHz, 10.75 W/m2) and LFN intensity (0-200 Hz, 72.9 dB) had a synergistic interaction effect, and the correct response time was statistically significantly prolonged by the combined exposure (F = 4.343, p < 0.05). The fNIRS imaging technique revealed a synergistic interaction effect between operational EMR intensity and operational LFN intensity, with statistically significant effects on the activation levels in the left and right dorsolateral prefrontal cortex (DLPFC). The mean ß values of DLPFC were significantly increased (L-DLPFC F = 5.391, p < 0.05, R-DLPFC F = 4.222, p < 0.05), and the relative concentrations of oxyhemoglobin in the DLPFC were also significantly increased (L-DLPFC F = 4.925, p < 0.05, R-DLPFC F = 9.715, p < 0.01). Conclusion: We found a statistically significant interaction effect between EMR (430.1357 MHz, 10.75 W/m2) and LFN (0-200 Hz, 72.9 dB) when simultaneously exposing subjects to both for 30 min. We conclude that exposure to this complex environment can cause a statistically significant increase in the MWL level of operators, and even alterations in their cognitive function.

SLC1A5 enhances malignant phenotypes through modulating ferroptosis status and immune microenvironment in glioma.

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune status prediction. Besides, SLC1A5 in the model could regulate the proliferation, invasion, ferroptosis and immune state in glioma, and be applied as a prognostic biomarker and potential therapeutic target for glioma.

Construction of an enzyme-free biosensor utilizing CuO nanoparticles enriched in DNA polymer to catalyze a click chemistry reaction for SERS detection of the p53 gene.

The p53 gene is a known cancer marker. We report a novel protocol for the SERS tandem strategy to detect the p53 gene with high sensitivity. Herein, the click reaction between azide and alkyne was catalyzed by utilizing copper oxide nanoparticles (CuONPs), which were enriched by a T-DNA-triggered hybridization chain reaction (HCR). The T-DNA signal was amplified by establishing the correlation between the T-DNA signal and the concentration of CuONPs in a nonenzymatic isothermal environment. In contrast to other Raman reporters, we used alkynyl compounds as Raman reporters, which showed excellent characteristics in the Raman-silent region (1800-2800 cm-1). Therefore, the highly sensitive and highly selective SERS signals could be obtained in complex biological matrices. Due to utilizing multistep amplification strategies, including the nanoparticle-modified HCR polymer and "click" reaction, the limit of detection (LOD) and the limit of quantification (LOQ) of this sensor could be as low as 0.0174 pM and 0.0583 pM, respectively. The accuracy of the strategy expressed as the RSD was in the range of 3.14%-6.21%. The results indicated that the constructed sensor has excellent performance for the detection of the p53 gene in serum samples in a low concentration range, which suggests that the proposed enzyme-free SERS analytical sensor has good clinical application prospects.

Fruitflow inhibits platelet function by suppressing Akt/GSK3ß, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets.

BACKGROUND: Platelets play an important role in the progression of atherosclerosis and cardiovascular events. The inhibition of platelet function is a main strategy to reduce risk of cardiovascular events. Some studies have shown that tomato extracts inhibit platelet function, but the molecular mechanisms remain unclear. Fruitflow is a water-solute tomato extract and the main ingredients including flavonoids, adenosine, chlorogenic acid, phytosterols, naringenin, and carotenoids. The present study investigated the effects of fruitflow on adenosine diphosphate (ADP)- and collagen- stimulated platelet aggregation, platelet adhesion, and levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (PGF1α), and platelet factor 4 (PF4) and explored the underlying molecular mechanisms. METHODS: Platelet-rich plasma (PRP) was used for measurement of platelet aggregation, TXB2, 6-keto- PGF1α, and PF4 levels. Platelet aggregation was analyzed using a Chrono-Log aggregometer. TXB2, 6-keto- PGF1α, and PF4 levels were determined using enzyme-linked immunosorbent assay kits. Immunoblotting was used to detect protein expression and phosphorylation on washed platelets. Platelet adhesion and spreading were determined by immunofluorescence. RESULTS: Fruitflow (1, 3, 10 and 100 µg/ml) dose-dependently inhibited platelet aggregation that was induced by ADP and collagen. Fruitflow (100 µg/ml) treatment completely suppressed ADP- and collagen-stimulated platelet aggregation. Fruitflow (100 µg/ml) significantly decreased TXB2 and 6-keto-PGF1α generation and PF4 release in ADP- and collagen-stimulated platelets. Treatment with fruitflow effectively blocked collagen-induced platelet spreading. To determine the potential molecule mechanism of action of fruitflow, we investigated the protein expression and phosphorylation of several signaling molecules in collagen-activated platelets. Fruitflow dose-dependently suppressed Akt, Glycogen synthase kinase-3ß (GSK-3ß), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) and p38 MAPK phosphorylation that was induced by collagen. CONCLUSION: Fruitflow inhibited platelet aggregation and reduced TXB2, 6-keto-PGF1α, and PF4 levels in ADP- and collagen-stimulated platelets. The mechanism of action of fruitflow may be associated with the suppression of Akt/GSK3ß, Syk/PLCγ2, and p38 MAPK phosphorylation in collagen-activated platelets. Fruitflow is a natural product derived from tomato and can be used as a health food for decreasing platelet activity.

Water-Soluble Tomato Extract Fruitflow Alters the Phosphoproteomic Profile of Collagen-Stimulated Platelets.

Platelet hyperactivity is a risk factor for cardiovascular disease and thrombosis. Recent studies reported that the tomato extract Fruitflow inhibited platelet function, but the molecular mechanism is still unclear. The present study used proteomics to quantitatively analyze the effect of fruitflow on the inhibition of collagen-stimulated platelets and validated the involvement of several signaling molecules. Fruitflow significantly inhibited human platelet aggregation and P-selectin expression that were induced by collagen. Proteomics analysis revealed that compared fruitflow-treated collagen-stimulated platelets with only collagen-stimulated platelets, 60 proteins were upregulated and 10 proteins were downregulated. Additionally, 66 phosphorylated peptides were upregulated, whereas 37 phosphorylated peptides were downregulated. Gene Ontology analysis indicated that fruitflow treatment downregulated phosphoinositide 3-kinase (PI3K)/protein kinase B and guanosine triphosphatase-mediated signal transduction in collagen-activated platelets. Biological validation indicated that fruitflow decreased Akt, glycogen synthase kinase 3ß, p38 mitogen-activated protein kinase (MAPK), and heat shock protein (Hsp27) phosphorylation in collagen-stimulated platelets. Fruitflow recovered cyclic adenosine monophosphate levels in collagen-activated platelets and reduced protein kinase A substrate phosphorylation that was induced by collagen. These findings suggest that fruitflow is a functional food that can inhibit platelet function, conferring beneficial effects for people who are at risk for platelet hyperactivity-associated thrombosis.

Resveratrol Confers Vascular Protection by Suppressing TLR4/Syk/NLRP3 Signaling in Oxidized Low-Density Lipoprotein-Activated Platelets.

This study investigated the effect of resveratrol on Toll-like receptor 4- (TLR4-) mediated matrix metalloproteinase 3 (MMP3) and MMP9 expression in oxidized low-density lipoprotein- (ox-LDL-) activated platelets and the potential molecule mechanism. Human platelets were used in the present study. The results showed that resveratrol suppressed TLR4, MMP3, and MMP9 expression in ox-LDL-activated platelets. The TLR4 inhibitor CLI-095 also inhibited MMP3 and MMP9 expression and secretion in ox-LDL- and lipopolysaccharide- (LPS-) activated platelets. The combination of resveratrol and CLI-095 synergistically suppressed MMP3 and MMP9 expression in ox-LDL- and LPS-activated platelets. These findings suggest that the resveratrol-induced inhibition of MMP3 and MMP9 expression is linked to the suppression of TLR4 activation. Resveratrol also suppressed spleen tyrosine kinase (Syk) phosphorylation and nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) expression and IL-1ß secretion in ox-LDL- and LPS-treated platelets. The coimmunoprecipitation results showed that resveratrol inhibited the binding of Syk and NLRP3. Finally, resveratrol reduced vascular senescence cells and the expression of TLR4, MMP3, and MMP9 and prevented alterations of vascular structure in 52-week-old mice. Our findings demonstrated that resveratrol decreased inflammatory protein expression and improved vascular structure in aged mice. Resveratrol inhibited the expression of TLR4 and secretion of MMP3, MMP9, and IL-1ß. The mechanism of action of resveratrol appears to be associated with the inhibition of TLR4/Syk/NLRP3 activation in ox-LDL-activated platelets.

Neprilysin gene transfer: A promising therapeutic approach for Alzheimer's disease.

Alzheimer's disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-ß (Aß) in the neuropil and around blood vessels, and formation of neurofibrillary tangles. Aß accumulation is considered the major pathological change in AD progression. In recent years, several therapeutic strategies for treating AD have focused on reducing the Aß burden in the brain. Among these approaches, the expression of Aß-degrading enzymes in the brain has been effective but, so far, impractical for treating patients. Neprilysin (NEP), the most prominent of the Aß-degrading enzymes in vivo, has been successfully delivered intracranially by viral vectors and is a promising therapeutic approach for reducing Aß accumulation and treating AD. However, some challenges are associated with the use of viral and nonviral vectors, including secondary toxicity, activation of the immune response, and low efficiency. Therefore, safe and efficient NEP delivery systems that could avoid the viral problems with minor injury and high transfection efficiency are required to deliver AD medical applications. This Mini-Review summarizes NEP gene transfer technologies that use viral and nonviral vectors and discusses the rationale and benefits of these delivery systems for AD treatment trials, providing a reference for basic and clinical studies on AD.