For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD‐like syndromes. However, the mechanisms of ...Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose‐ and time‐dependently blocks the protein translation of amyloid precursor protein (APP) and heavy‐chain Ferritin (H‐Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H‐Ferritin are post‐transcriptionally regulated by iron responsive proteins, which bind to homologous iron responsive elements (IREs) located in the 5′‐untranslated regions (5′‐UTRs) within their mRNA transcripts. Using reporter assays, we demonstrate that Mn exposure repressed the 5′‐UTR‐activity of APP and H‐Ferritin, presumably via increased iron responsive proteins‐iron responsive elements binding, ultimately blocking their protein translation. Using two specific Fe2+‐specific probes (RhoNox‐1 and IP‐1) and ion chromatography inductively coupled plasma mass spectrometry (IC‐ICP‐MS), we show that loss of the protective axis of APP and H‐Ferritin resulted in unchecked accumulation of redox‐active ferrous iron (Fe2+) fueling neurotoxic oxidative stress. Enforced APP expression partially attenuated Mn‐induced generation of cellular and lipid reactive oxygen species and neurotoxicity. Lastly, we could validate the Mn‐mediated suppression of APP and H‐Ferritin in two rodent in vivo models (C57BL6/N mice and RjHan:SD rats) mimicking acute and chronic Mn exposure. Together, these results suggest that Mn‐induced neurotoxicity is partly attributable to the translational inhibition of APP and H‐Ferritin resulting in impaired iron metabolism and exacerbated neurotoxic oxidative stress.
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For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD‐like syndromes. Here, we demonstrate that Mn exposure results in suppression of amyloid precursor protein (APP) and H‐Ferritin in vitro and in vivo. On the molecular level, it could be shown that Mn inhibits the protein translation via repressing the 5’‐UTR activity of both proteins. Mn‐mediated suppression of both iron‐regulating proteins results in an accumulation of redox‐active iron (Fe2+) that fuels neurotoxic cellular oxidative stress and lipidperoxidation. APP overexpression significantly attenuate Mn‐induced oxidative stress and neurotoxicity. The implications that Mn exposure results in a translational suppression of APP and H‐Ferritin links a disturbed iron homeostasis with Mn‐induced oxidative neurotoxicity.
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Abstract
Artificial chiral materials and nanostructures with strong and tuneable chiroptical activities, including sign, magnitude, and wavelength distribution, are useful owing to their potential ...applications in chiral sensing, enantioselective catalysis, and chiroptical devices. Thus, the inverse design and customized manufacturing of these materials is highly desirable. Here, we use an artificial intelligence (AI) guided robotic chemist to accurately predict chiroptical activities from the experimental absorption spectra and structure/process parameters, and generate chiral films with targeted chiroptical activities across the full visible spectrum. The robotic AI-chemist carries out the entire process, including chiral film construction, characterization, and testing. A machine learned reverse design model using spectrum embedded descriptors is developed to predict optimal structure/process parameters for any targeted chiroptical property. A series of chiral films with a dissymmetry factor as high as 1.9 (
g
abs
~ 1.9) are identified out of more than 100 million possible structures, and their feasible application in circular polarization-selective color filters for multiplex laser display and switchable circularly polarized (CP) luminescence is demonstrated. Our findings not only provide chiral films with the highest reported chiroptical activity, but also have great fundamental value for the inverse design of chiroptical materials.
Sensitivity experiments were conducted on Typhoon Mujigae, which occurred in 2015, wherein the Weather Research and Forecasting Advanced Research (WRF-ARW) model was used to select two local and two ...nonlocal planetary boundary layer (PBL) parameterization schemes: the quasi-normal scale elimination (QNSE) and Mellor–Yamada–Janjic (MYJ) schemes, and the Yonsei University (YSU) and medium-range forecast (MRF) schemes, respectively. The differences in rainfall response in the typhoon’s inner core and outer region were evaluated by comparing the anomaly rainfall distribution, heat transmission, and mixing processes in the boundary layer among the PBL schemes. The results show that the simulated rainfall in typhoon Mujigae has large uncertainty among the PBL schemes and a significant difference between the inner and outer regions. Compared with the observation, the simulated rainfall was significantly higher in the inner core and slightly lower in the outer region. All PBL schemes accurately identified the rainfall location, although the amounts differed between the schemes. The rainfall levels in the MRF scheme were closest to the observation, followed by those in the YSU and MYJ schemes; the QNSE scheme showed the largest deviation. In general, rainfall simulation using a nonlocal boundary layer scheme such as MRF had the best results for both the inner core and the outer region.
Background
This study aimed to examine attentional bias (AB) for sad and social rejection words in Chinese left‐behind children (LBC) with depression.
Method
We investigated both stimulus specificity ...and components of AB in different groups using a cross‐sectional design. Data were drawn from a school assessment of depression and anxiety, from which we selected LBC with depression (n = 40), LBC without depression (n = 33), a control group with depression (n = 31), and a control group without depression (n = 37). AB was measured with a dot‐probe task covering two stimulus types (sad and rejection).
Results
The analysis of AB scores revealed a significant three‐way interaction (LBC × depression × word type), F(1, 137) = 4.00, p = 0.047, η2 = 0.028, with depressed non‐LBC exhibiting a significant depression × word type interaction, F(1, 66) = 4.67, p = 0.034, η2 = 0.066, while the depression × word type interaction was not significant in LBC, F(1, 71) = 0.18, p = 0.675, η2 = 0.002. Depressed children living with their parents showed AB towards sad words but not rejection words, while depressed LBC showed greater AB towards both rejection and sad words.
Conclusions
The findings provide evidence that an AB towards sad information is critically involved in the depressed LBC. Compared with non‐LBC depressed individuals, an AB for rejection may be involved as a risk factor in the LBC. It sheds light on the effective intervention programmes for LBC's depression and have important practical significance for reducing depression and improving the mental health of LBC.
Label-free data mining can efficiently feed large amounts of data from the vast scientific literature into artificial intelligence (AI) processing systems. Here, we demonstrate an unsupervised ...syntactic distance analysis (SDA) approach that is capable of mining chemical substances, functions, properties, and operations without annotation. This SDA approach was evaluated in several areas of research from the physical sciences and achieved performance in information mining comparable to that of supervised learning, as shown by its satisfactory scores of 0.62–0.72, 0.60–0.82, and 0.86–0.95 in precision, recall, and accuracy, respectively. We also showcase how our approach can assist robotic chemists programmed to perform research focused on double-perovskite colloidal nanocrystals, gold colloidal nanocrystals, oxygen evolution reaction catalysts, and enzyme-like catalysts by designing materials, formulations, and synthesis parameters based on data mined from 1.1 million literature references.
Human hepatoma (HCC) has been reported to be strongly resistant to Fas-mediated apoptosis. However, the underlying mechanisms are poorly understood. In this study the function of oxysterol-binding ...protein-related protein 8 (ORP8) in human hepatoma cells apoptosis was assessed. We found that ORP8 is down-regulated, whereas miR-143, which controls ORP8 expression, is up-regulated in clinical HCC tissues as compared with liver tissue from healthy subjects. ORP8 overexpression triggered apoptosis in primary HCC cells and cell lines, which coincided with a relocation of cytoplasmic Fas to the cell plasma membrane and FasL up-regulation. Co-culture of HepG2 cells or primary HCC cells with Jurkat T-cells or T-cells, respectively, provided further evidence that ORP8 increases HCC cell sensitivity to Fas-mediated apoptosis. ORP8-induced Fas translocation is p53-dependent, and FasL was induced upon ORP8 overexpression via the endoplasmic reticulum stress response. Moreover, ORP8 overexpression and miR-143 inhibition markedly inhibited tumor growth in a HepG2 cell xenograft model. These results indicate that ORP8 induces HCC cell apoptosis through the Fas/FasL pathway. The role of ORP8 in Fas translocation to the plasma membrane and its down-regulation by miR-143 offer a putative mechanistic explanation for HCC resistance to apoptosis. ORP8 may be a potential target for HCC therapy.
Background: The mechanism of HCC resistant to Fas-mediated apoptosis is not clearly understood.
Results: ORP8 triggered HCC cell apoptosis via relocation of cytoplasmic Fas to the cell plasma membrane and FasL up-regulation.
Conclusion: ORP8 increases sensitivity of HCC cells to Fas-mediated apoptosis.
Significance: New insights reveal that ORP8 may serve as a potential target for HCC therapy.
Rationale: The most common complications of vacuum-assisted removal (VAR) for benign breast masses are hematoma, infection, and occasionally pseudoaneurysms. To the best of our knowledge, this is the ...first report of a true aneurysm following VAR for breast fibroadenomas. Case Presentation: A 50-year-old woman underwent VAR of bilateral benign breast masses under ultrasonic guidance. Routine breast ultrasound examination was performed 3 months later, and no discomfort was observed during follow-up. Diagnoses and Interventions: Physical examination revealed a slightly palpable, arterial like pulsation in the lateral part of the right breast. The two-dimensional ultrasound showed that there was a well-defined anechoic nodule in the right breast at the 9 o'clock position 3 cm from the nipple, measuring 6 mm * 4 mm. Color Doppler sonography demonstrated that it was a localized dilated intramammary arteriole within the colorful flow. Spectral Doppler illustrated a high-velocity turbulent arterial flow component inside. Based on these findings, the patient was diagnosed with an iatrogenic true aneurysm of the breast. Given her overall good condition, conservative treatment with regular imaging surveillance was adopted. Outcomes: Up to now, the patient remains asymptomatic, and the size of the aneurysm has not changed. Lessons: With the increasing use of interventional diagnosis and treatment techniques, iatrogenic vascular complications are likely to occur more frequently. Careful duplex ultrasound examination prior to or following the procedure is strongly recommended. In the absence of risk factors, we recommend a conservative approach to small, stable aneurysms. Keywords: ultrasound, breast, true aneurysm, conservative treatment
Purpose: This study investigated the effectiveness and feasibility of shear wave elastography ((sound touch elastography) STE and (shear wave elastography) SWE) and visual transient elastography ...(ViTE) in the noninvasive quantitative diagnosis of liver fibrosis in chronic liver disease (CLD). Patients and Methods: A total of 106 patients with CLD underwent STE, SWE and ViTE elastography evaluation. The Young's modulus of the three elastography was valuated and the diagnostic performances of the three techniques for liver fibrosis staging were compared. The area under the receiver operating curve (ROC) for the diagnosis of liver fibrosis was compared. The final diagnosis was based on the histological findings on the liver biopsy. Results: 1) The correlation between ViTE and SWE, ViTE and STE, SWE and STE stiffiness values were 0.72, 0.75, 0.75 (P<0.001). 2) The relationship between the results of each elastography technique and the stage of pathological liver fibrosis showed that the more severe the liver fibrosis was, the higher the stiffiness value was (all P <0.001). 3) When the three elastography techniques were used to detect the degree of liver fibrosis in different pathological stages, there was no statistical difference in the stabilities of the boxplots. 4) The ROCs of the three elastography techniques (ViTE, SWE and STE) were 0.88, 0.91, 0.92, F0 vs F1-3; 0.84, 0.84, 0.84, F0-1 vs F2-4; 0.80, 0.79, 0.77, F0-2 vs F3-4; 0.80, 0.76, 0.71, F0-3 vs 4; the AUC of ViTE was higher than the AUC of STE in the identification of F4, but there were no statistical differences in the AUCs of other groups. Conclusion: ViTE has good stability for the liver stiffiness measurement (LSM) and a high consistency with shear-wave elastography (SWE and STE). It is an effective tool for evaluating CLD, and its performance is comparable to SWE and STE. The combination of ViTE and STE can improve the specificity of disease diagnosis and do not add extra cost and may improve cost performance. Keywords: chronic liver disease, liver fibrosis, shear wave elastography, visual transient elastography, liver stiffiness measurement
The realization of automated chemical experiments by robots unveiled the prelude to an artificial intelligence (AI) laboratory. Several AI-based systems or robots with specific chemical skills have ...been demonstrated, but conducting all-round scientific research remains challenging. Here, we present an all-round AI-Chemist equipped with scientific data intelligence that is capable of performing basic tasks generally required in chemical research. Based on a service platform, the AI-Chemist is able to automatically read the literatures from a cloud database and propose experimental plans accordingly. It can control a mobile robot in-house or online to automatically execute the complete experimental process on 14 workstations, including synthesis, characterization and performance tests. The experimental data can be simultaneously analysed by the computational brain of the AI-Chemist through machine learning and Bayesian optimization, allowing a new hypothesis for the next iteration to be proposed. The competence of the AI-Chemist has been scrutinized by three different chemical tasks. In the future, the more advanced all-round AI-Chemists equipped with scientific data intelligence may cause changes to the landscape of the chemical laboratory.
The most common complications of vacuum-assisted removal (VAR) for benign breast masses are hematoma, infection, and occasionally pseudoaneurysms. To the best of our knowledge, this is the first ...report of a true aneurysm following VAR for breast fibroadenomas.
A 50-year-old woman underwent VAR of bilateral benign breast masses under ultrasonic guidance. Routine breast ultrasound examination was performed 3 months later, and no discomfort was observed during follow-up.
Physical examination revealed a slightly palpable, arterial-like pulsation in the lateral part of the right breast. The two-dimensional ultrasound showed that there was a well-defined anechoic nodule in the right breast at the 9 o'clock position 3 cm from the nipple, measuring 6 mm × 4 mm. Color Doppler sonography demonstrated that it was a localized dilated intramammary arteriole within the colorful flow. Spectral Doppler illustrated a high-velocity turbulent arterial flow component inside. Based on these findings, the patient was diagnosed with an iatrogenic true aneurysm of the breast. Given her overall good condition, conservative treatment with regular imaging surveillance was adopted.
Up to now, the patient remains asymptomatic, and the size of the aneurysm has not changed.
With the increasing use of interventional diagnosis and treatment techniques, iatrogenic vascular complications are likely to occur more frequently. Careful duplex ultrasound examination prior to or following the procedure is strongly recommended. In the absence of risk factors, we recommend a conservative approach to small, stable aneurysms.
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