Single isocenter versus dual isocenter treatment using flattening filter-free and jaw-tracking volumetrically modulated arc therapy for boot-shaped lung cancer: Evaluation of dosimetric and feasibility.

BACKGROUND: To determine whether a dual-isocenter volumetrically modulated arc therapy (VMAT) technique results in lower normal pulmonary dosage compared to a traditional single isocenter technique for boot-shaped lung cancer. METHODS: A cohort of 15 patients with advanced peripheral or central lung cancer who had metastases in the mediastinum and supraclavicular lymph nodes was randomly selected for this retrospective study. VMAT plans were generated for each patient using two different beam alignment techniques with the 6-MV flattening filter-free (FFF) photon beam: single-isocenter jaw-tracking VMAT based on the Varian TrueBeam linear accelerator (S-TV), and dual-isocenter VMAT based on both TrueBeam (D-TV) and Halcyon linear accelerator (D-HV). For all 45 treatment plans, planning target volume (PTV) dose coverage, conformity/homogeneity index (CI/HI), mean heart dose (MHD), mean lung dose (MLD) and the total lung tissue receiving 5, 20, 30 Gy (V5, V20, V30) were evaluated. The monitor units (MUs), delivery time, and plan quality assurance (QA) results were recorded. RESULTS: The quality of the objectives of the three plans was comparable to each other. In comparison with S-TV, D-TV and D-HV improved the CI and HI of the PTV (p < 0.05). The MLD was 13.84 ± 1.44 Gy (mean ± SD) for D-TV, 14.22 ± 1.30 Gy and 14.16 ± 1.42 Gy for S-TV and D-HV, respectively. Lungs-V5Gy was 50.78 ± 6.24%, 52.00 ± 7.32% and 53.36 ± 8.48%, Lungs-V20Gy was 23.72 ± 2.27%, 26.18 ± 2.86% and 24.96 ± 3.09%, Lungs-V30Gy was 15.69 ± 1.76%, 17.20 ± 1.72% and 16.52 ± 2.07%. Compared to S-TV, D-TV provided statistically significant better protection for the total lung, with the exception of the lungs-V5. All plans passed QA according the gamma criteria of 3%/3 mm. CONCLUSIONS: Taking into account the dosimetric results and published clinical data on radiation-induced pulmonary injury, dual-isocenter jaw-tracking VMAT may be the optimal choice for treating boot-shaped lung cancer.

Complexity-based graph convolutional neural network for epilepsy diagnosis in normal, acute, and chronic stages.

Introduction: The automatic precision detection technology based on electroencephalography (EEG) is essential in epilepsy studies. It can provide objective proof for epilepsy diagnosis, treatment, and evaluation, thus helping doctors improve treatment efficiency. At present, the normal and acute phases of epilepsy can be well identified through EEG analysis, but distinguishing between the normal and chronic phases is still tricky. Methods: In this paper, five popular complexity indicators of EEG signal, including approximate entropy, sample entropy, permutation entropy, fuzzy entropy and Kolmogorov complexity, are computed from rat hippocampi to characterize the normal, acute, and chronic phases during epileptogenesis. Results of one-way ANOVA and principal component analysis both show that utilizing complexity features, we are able to easily identify differences between normal, acute, and chronic phases. We also propose an innovative framework for epilepsy detection based on graph convolutional neural network (GCNN) using multi-channel EEG complexity as input. Results: Combining information of five complexity measures at eight channels, our GCNN model demonstrate superior ability in recognizing the normal, acute, and chronic phases. Experiments results show that our GCNN model reached the high prediction accuracy above 98% and F1 score above 97% among these three phases for each individual rat. Discussion: Our research practice based on real data shows that EEG complexity characteristics are of great significance for recognizing different stages of epilepsy.

A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS.

Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the Food and Drug Administration-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, a carrier-free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18ß-Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half-life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.

The new smart city programme: Evaluating the effect of the internet of energy on air quality in China.

The internet of energy conforms to the trend of clean, electrified, networked, and intelligent urban energy systems and is a new solution for the green development of smart cities. Using air-quality-index big data from official publications for 2018 to 2019, this study performs a quasi-natural experiment to assess the impact of internet of energy demonstration projects in China. Using a difference-in-difference test, it is found that this initiative improves the air quality of pilot cities. After estimating a spatial panel regression model, we find that the spatial radiation effect of the policy indicates that the air quality around the pilot city is also improved. This study provides empirical evidence for the promotion and application of internet of energy projects.

Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing.

Deposition of amyloid ß (Aß) to form neuritic plaques in the brain is the pathological hallmark of Alzheimer's disease (AD). Aß is generated from sequential cleavages of the ß-amyloid precursor protein (APP) by the ß- and γ-secretases, and ß-site APP-cleaving enzyme 1 (BACE1) is the essential ß-secretase for Aß generation. Vulnerable regions in AD brains show increased BACE1 protein levels. However, the underlying mechanism how BACE1 is regulated remains to be further illustrated. Nuclear Factor of Activated T-cells (NFAT) has been implicated in AD pathogenesis. Despite the increasing appreciation for the importance of NFAT-dependent transcription in the nervous system, the regulation and function of specific NFAT isoforms in neurons is poorly understood. In this report we found that both BACE1 and NFAT3 levels were significantly increased in the brains of APP/PS1 transgenic mice. We found that overexpression of NFAT3 resulted in increase of BACE1 promoter activity and BACE1 transcription, while disruption of NFAT3 expression decreased BACE1 gene transcription and protein expression in SAS1 cells. In a addition, overexpression of NFAT3 leads to increase levels of Aß production. Chromatin immunoprecipitation analysis revealed direct binding of NFAT3 to specific DNA sequences within BACE1 promoter region. Taken together, our results indicate that NFAT is a BACE1 transcription factor. Our study suggests that inhibition of NFAT-mediated BACE1 expression may be a valuable drug target for AD therapy.

Cryptotanshinione upregulates alpha-secretase by activation PI3K pathway in cortical neurons.

The amyloid precursor protein (APP) is cleaved enzymatically by nonamyloidogenic and amyloidogenic pathways. alpha-Secretase cleaves APP within beta amyloid protein (Abeta) sequence, resulting in the release of a secreted fragment of APP (sAPPalpha) and precluding Abeta generation. Cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of Alzheimer's disease (AD). We have shown previously that CTS modulated APP metabolism by elevation alpha-secretase activity. However, the molecular mechanisms involved were unclear. Here we reported that CTS increased alpha-secretase activity and sAPPalpha release. To gain insight into the molecular mechanism whereby CTS modulates alpha-secretase, we evaluated the involvement of three candidate alpha-secretase enzymes, a-disintegrin and metalloprotease (ADAM) 9, 10, or 17, in CTS-induced non-amyloidogenic APP metabolism. Results showed that CTS treatment of cortical neurons overexpressing Swedish mutant human APP695 markedly elevated ADAM10 protein, and the inhibitor of ADAM10 inhibited the CTS-induced increase in alpha-secretase activity, suggesting CTS modulated alpha-secretase activity by upregulation ADAM10 protein. By using several specific protein kinase inhibitors, we showed that phosphatidylinositol 3-kinase (PI3K) mediated the CTS-induced alpha-secretase activation.