Tau Hyperphosphorylation is Associated with Spatial Learning and Memory After Exposure to Benzo[a]pyrene in SD Rats

As a representative substance of the polycyclic aromatic hydrocarbons, benzo[a]pyrene (B[a]P) is a widely distributed environmental contaminant. Several studies have indicated that B[a]P exposure could impair learning and memory function in human population and animal models. Abnormal hyperphosphorylation and aggregation of microtubule-associated protein tau play a crucial role in neurodegenerative diseases manifesting deficits of learning and memory. In the present study, we investigated the involvement of tau hyperphosphorylation in memory impairment after espousing to B[a]P in SD rats. Male SD rats were randomly divided into five groups: the blank control group received no treatment and the others received intraperitoneal injection of B[a]P (0, 1.0, 2.5, 6.25 mg/kg bw) for 1, 2, and 3 months, respectively. Morris water maze was employed to observe the learning and memory impairment. To find the relationship between cognitive functions and tau protein, we measured the site-specific phosphorylation of tau at Ser199, Ser396, Thr181, and Thr231, which are related with spatial and memory deficits in the brain of rats. The spatial and learning of rats were impaired after exposing to B[a]P for 1 month, so as 2 and 3 months compared to blank control groups, respectively. Rats exposed to 2.5 and 6.25 mg/kg bw B[a]P for either 2 or 3 months had modified behavior compared to control as indicated by the increased latencies, increased the first time arriving at the target space and decreased number crossing the platform and time in target quadrant. B[a]P led to tau hyperphosphorylation at Ser199, Thr181, and Thr231 epitopes. And with time and dose expanded, tau protein, Ser199, Thr181, and Thr231 expression increased. However, the differences in expression of Ser396 at different doses or points were not statistically significant. Moreover, we observed a correlation between memory impairments and tau phosphorylation levels. The present results indicate that Tau hyperphosphorylation is associated with the observed deficits in spatial learning and memory following exposure to B[a]P in SD rats.     

Isolation and Characterization of Two New Deoxynivalenol-Degrading Strains,Bacillus sp. HN117 and Bacillus sp. N22

Deoxynivalenol (DON), produced by Fusarium species, is one of the most common trichothecenes detected in cereals pre- and post-harvest, which poses a great threat to the health of livestock and human beings due to its strong toxicity. In this study, we isolated and characterized two DON-degrading bacterial strains, Bacillus sp. HN117 and Bacillus sp. N22. Both strains could degrade DON efficiently in a wide range of temperatures (from 25 °C to 42 °C) and concentrations (from 10 mg/L to 500 mg/L). After optimization of the degradation conditions, 29.0% DON was eliminated by HN117 in 72 h when it was incubated with 1000 mg/L DON; meanwhile, the DON degradation rate of N22 was boosted notably from 7.41% to 21.21% within 120 h at 500 mg/L DON. Degradation products analysis indicated HN117 was able to transform DON into a new isomer M-DOM, the possible structure of which was deduced based on LC-MS and NMR analysis, and N22 could convert DON into potential low-toxic derivatives norDON E and 9-hydroxymethyl DON lactone. These two strains have the potential to be developed as new biodegrading agents to control DON contamination in food and feed industries.     

Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients

BackgroundThere is accumulating evidence that autophagic activity is crucial to the development of hepatocellular carcinoma (HCC). Thus, we sought to develop a predictive model based on autophagy-related genes (ARGs) to forecast the prognosis of HCC patients.MethodsBased on expression data from The Cancer Genome Atlas (TCGA) and ARGs from Human Autophagy Database (HADb), the differentially expressed ARGs were screened. The prognosis-related ARGs were identified using a univariate Cox regression analysis. Using multivariate Cox regression analysis, a prognostic model was developed. To assess the predictive value of the model, receiver operating characteristic (ROC) curve, Kaplan-Meier curve, and multivariable Cox regression analyses were conducted. A data cohort gathered independently from the International Cancer Genome Consortium (ICGC) database further verified the model’s predictive accuracy. The immune landscape was generated using the TIMER and CIBERSORT algorithms. Finally, the correlation between the prognostic signature and gene mutation status was analyzed by employing “maftools” package.ResultsWe identified a novel prediction model based on the ARGs of PLD1 and SLC36A1 with significant prognostic values for HCC in both univariate and multivariate Cox regression analysis, and patients were classified into high- or low-risk groups based on their risk scores. High-risk patients had significantly shorter overall survival (OS) times than low-risk patients (P=5e-4). According to the ROC curve analysis, the risk score had a higher predictive value than the other clinical characteristics. Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with HCC. Further, an external independent cohort of ICGC patients provided additional confirmation of the predictive efficacy of the model. We subsequently analyzed the differential immune densities of the two groups and discovered that various immune cells, including naïve B cells, resting memory cluster of differentiation (CD)4 T cells, regulatory T cells, M2 macrophages, and neutrophils, had considerably larger infiltrating densities in the high-risk group than the low-risk group.ConclusionsWe established a robust autophagy-related risk model having a certain prediction accuracy for predicting the prognosis of HCC patients. Our findings will contribute to the definition of prognosis and establishment of personalized treatment interventions for HCC patients.     

Investigation on the Fatigue Crack Propagation of Medium-Entropy Alloys with Heterogeneous Microstructures

The behavior and the mechanism of fatigue crack propagation in CrCoNi medium-entropy alloys (MEAs) with heterogeneous microstructures were investigated in this paper. After cold-rolling and recrystallization annealing at different temperatures and times, five sets of heterostructured specimens were acquired with different recrystallization levels. Then, the structure characterizations of these five sets of specimens were carried out by nanoindentation testing and electron back-scatter diffraction (EBSD) mapping. Finally, the fatigue crack propagation tests were conducted on single edge crack specimens of these different heterogeneous microstructures. The experimental results indicate that the crack propagation rates of specimens with partial recrystallization microstructures are higher than those with complete recrystallization microstructures, and the effect on fatigue crack thresholds of these specimens is the opposite. The fatigue cracks grow along the slip planes or twin boundaries in recrystallization grains (RGs), which induced crack deflections and the roughness-induced crack closure effect. For this reason, the area percentage of recrystallization and the grain size of RGs have a great effect on the value of the fatigue crack growth threshold.     

Unveiling the Effect of CaF2 on the Microstructure and Transport Properties of Phosphosilicate Systems

As an effective flux, CaF₂ is beneficial in improving the fluidity of slag in the steel-making process, which is crucial for dephosphorization. To reveal the existence form and functional mechanism of CaF₂ in phosphosilicate systems, the microstructures and transport properties of CaO-SiO₂-CaF₂-P₂O₅ quaternary slag systems are investigated by molecular dynamics simulations (MD) combined with experiments. The results demonstrate that the Si-O coordination number does not vary significantly with the increasing CaF₂ content, but the P-O coordination number dramatically decreases. CaF₂ has a minor effect on the single [SiO₄] but makes the structure of the silicate system simple. On the contrary, F⁻ ions could reduce the stability of P-O bonds and promoted the transformation of [PO₄] to [PO₃F], which is beneficial for making the P element-enriched phosphate network structure more aggregated. However, the introduction of CaF₂ does not alter the tetrahedral character of the original fundamental structural unit. In addition, the results of the investigation of the transport properties show that the self-diffusion coefficients of each ion are positively correlated with CaF₂ content and arranged in the order of F⁻ > Ca²⁺ > O²⁻ ≈ P⁵⁺ > Si⁴⁺. Due to CaF₂ reducing the degree of polymerization of the whole melts, the viscosity decreases from 0.39 to 0.13 Pa·s as the CaF₂ content increases from 0% to 20%. Moreover, the viscosity of the melt shows an excellent linear dependence on the structural parameters.     

SLC18A3 promoted renal cancer development through acetylcholine/cAMP signaling

Renal cancer displays a high metastatic potential and a poor response to chemotherapy. However, the critical contributors to renal cancer development remain elusive. This study focused on acetylcholine (ACh) signaling. We identified the vesicular acetylcholine transporter (SLC18A3) that upregulates in patients with renal cancer. We further discovered that SLC18A3 enhanced the uptake of ACh, a classical neurotransmitter mediating synaptic transmission. The elevated ACh activated the protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, which contributed to renal cancer cell proliferation and invasive migration. Consistently, SLC18A3 overexpression caused sustained tumor growth and increased lung metastases in A489-bearing mice. In summary, our study demonstrated that SLC18A3 contributed to cancer spread in an ACh/PKA/CREB-dependent manner, which may drive the design of efficacious treatment strategies.