Truemarks1095
Hypoxia is a universal feature in the tumor microenvironment (TME). Nonetheless, the heterogeneous hypoxia patterns of TME have still not been elucidated in hepatocellular carcinoma (HCC). Using consensus clustering algorithm and public datasets, we identified heterogeneous hypoxia subtypes. We also revealed the specific biological and clinical characteristics via bioinformatic methods. The principal component analysis algorithm was employed to develop a hypoxia-associated risk score (HARS). We identified the two hypoxia subtypes low hypoxia pattern (C1) and high hypoxia pattern (C2). C1 was less sensitive to immunotherapy compared to C2, consistent with the lack of immune cells and immune checkpoints (ICPs) in C1, whereas C2 was the opposite. C2 displayed worse prognosis and higher sensitivity to obatoclax relative to C1, while C1 was more sensitive to sorafenib. The two subtypes also demonstrated subtype-specific genomic variations including mutation, copy number alteration, and methylation. Moreover, we developed and validated a risk signature HARS, which had excellent performance for predicting prognosis and immunotherapy. We revealed two hypoxia subtypes with distinct biological and clinical characteristics in HCC, which enhanced the understanding of hypoxia pattern. The risk signature was a promising biomarker for predicting prognosis and immunotherapy.Recently, increasing attention has been paid to the correlation between the expression of downstream of kinase 7 (DOK7) and the occurrence and development of various tumors. In this study, we clarified the effects of DOK7 in breast cancer. First, we showed that DOK7 expression was obviously reduced in the breast cancer tissues and lower levels of DOK7 linked to more aggressive behaviors and worse prognosis of patients. Furthermore, DOK7 expression of various breast cancer cell lines was lower than that of human noncancerous MCF-10A cells. Overexpression of DOK7 inhibited proliferation, migration, and invasion, while silencing DOK7 expression promoted the malignancy of breast cancer. In addition, overexpression of DOK7 suppressed tumor proliferation and lung metastasis in animal models. Finally, to investigate the possible signaling mechanism, we first found that the level of p-AKT protein was extremely downregulated and the level of PTEN protein was remarkably upregulated after overexpressing DOK7 in breast cancer cells. Repression of PTEN expression using PTEN siRNA or SF1670 (PTEN inhibitor) rescued the tumor-inhibiting effect induced by DOK7 overexpression, suggesting that DOK7 inhibits proliferation, migration, and invasion of breast cancer cells though the PI3K/PTEN/AKT pathway. this website These results suggest that the downregulation of DOK7 may become a novel breast cancer therapeutic target.
The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [
Y]Y/[
Lu]Lu-DOTATATE.
. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [
Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [
Y]Y/[
Lu]Lu-DOTATATE (1 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria.
The median follow-up was 88 months (the range 42-164). The median cumulative administered activity was 22.2 GBq (the range 17.8-30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3-6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively.
The repeated therapy with [
Y]Y/[
Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.
The repeated therapy with [90Y]Y/[177Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.Mental fatigue is a common psychobiological state elected by prolonged cognitive activities. Although, the performance and the disadvantage of the mental fatigue have been well known, its connectivity among the multiareas of the brain has not been thoroughly studied yet. This is important for the clarification of the mental fatigue mechanism. However, the common method of connectivity analysis based on EEG cannot get rid of the interference from strong noise. In this paper, an adaptive feature extraction model based on stacked denoising autoencoder has been proposed. The signal to noise ratio of the extracted feature has been analyzed. Compared with principal component analysis, the proposed method can significantly improve the signal to noise ratio and suppress the noise interference. The proposed method has been applied on the analysis of mental fatigue connectivity. The causal connectivity among the frontal, motor, parietal, and visual areas under the awake, fatigue, and sleep deprivation conditions has been analyzed, and different patterns of connectivity between conditions have been revealed. The connectivity direction under awake condition and sleep deprivation condition is opposite. Moreover, there is a complex and bidirectional connectivity relationship, from the anterior areas to the posterior areas and from the posterior areas to the anterior areas, under fatigue condition. These results imply that there are different brain patterns on the three conditions. This study provides an effective method for EEG analysis. It may be favorable to disclose the underlying mechanism of mental fatigue by connectivity analysis.Neuropathic pain is a public health problem. Although many pharmaceuticals are used to treat neuropathic pain, effective and safe drugs do not yet exist. In this study, we tested nociceptive responses in CCI rats, and ELISA assay was performed to examine the expression of proinflammatory cytokines. We found that amorfrutins significantly reduce the pain behaviors in CCI rats and suppress the expression of proinflammatory cytokines (TNFα, IL-6, and IL-1β) and chemokines (CCL2/CCR2) in the spinal cord. However, concurrent administration of a PPARγ antagonist, GW9662, reversed the antihyperalgesic effect induced by amorfrutins. The results indicate that amorfrutins inhibit the inflammation and chemokine expression by activating PPARγ, thus relieving neuropathic pain in CCI rats. Therefore, PPARγ-CCL2/CCR2 pathway might represent a new treatment option for neuropathic pain.One of the major shortcomings of Hopfield neural network (HNN) is that the network may not always converge to a fixed point. HNN, predominantly, is limited to local optimization during training to achieve network stability. In this paper, the convergence problem is addressed using two approaches (a) by sequencing the activation of a continuous modified HNN (MHNN) based on the geometric correlation of features within various image hyperplanes via pixel gradient vectors and (b) by regulating geometric pixel gradient vectors. These are achieved by regularizing proposed MHNNs under cohomology, which enables them to act as an unconventional filter for pixel spectral sequences. It shifts the focus to both local and global optimizations in order to strengthen feature correlations within each image subspace. As a result, it enhances edges, information content, contrast, and resolution. The proposed algorithm was tested on fifteen different medical images, where evaluations were made based on entropy, visual information fidelity (VIF), weighted peak signal-to-noise ratio (WPSNR), contrast, and homogeneity. Our results confirmed superiority as compared to four existing benchmark enhancement methods.In this paper, we study the nonnegativity and stability properties of the solutions of a newly proposed extended SEIR epidemic model, the so-called SE(Is)(Ih)AR epidemic model which might be of potential interest in the characterization and control of the COVID-19 pandemic evolution. The proposed model incorporates both asymptomatic infectious and hospitalized infectious subpopulations to the standard infectious subpopulation of the classical SEIR model. In parallel, it also incorporates feedback vaccination and antiviral treatment controls. The exposed subpopulation has three different transitions to the three kinds of infectious subpopulations under eventually different proportionality parameters. The existence of a unique disease-free equilibrium point and a unique endemic one is proved together with the calculation of their explicit components. Their local asymptotic stability properties and the attainability of the endemic equilibrium point are investigated based on the next generation matrix properties, the value of the basic reproduction number, and nonnegativity properties of the solution and its equilibrium states. The reproduction numbers in the presence of one or both controls is linked to the control-free reproduction number to emphasize that such a number decreases with the control gains. We also prove that, depending on the value of the basic reproduction number, only one of them is a global asymptotic attractor and that the solution has no limit cycles.N-containing aromatic compounds (NACs) are an important group of light-absorbing molecules in the atmosphere. They are often observed in combustion emissions, but their chemical formulas and structural characteristics remain uncertain. In this study, red oak wood and charcoal fuels were burned in cookstoves using the standard water boiling test (WBT) procedure. Submicron aerosol particles in the cookstove emissions were collected using quartz (Q f ) and polytetrafluoroethylene (PTFE) filter membranes positioned in parallel. A back-up quartz filter (Q b ) was also installed downstream of the PTFE filter to evaluate the effect of sampling artifact on NACs measurements. Liquid chromatography-mass spectroscopy (LC-MS) techniques identified seventeen NAC chemical formulas in the cookstove emissions. The average concentrations of total NACs in Q b samples (0.37 ± 0.31 - 1.79 ± 0.77 μg m-3) were greater than 50% of those observed in the Q f samples (0.51 ± 0.43 - 3.91 ± 2.06 μg m-3), and the Q b to Q f mass ratios of individual NACs had a range of 0.02 - 2.71, indicating that the identified NACs might have substantial fractions remaining in the gas-phase. In comparison to other sources, cookstove emissions from red oak or charcoal fuels did not exhibit unique NAC structural features, but had distinct NACs composition. However, before identifying NACs sources by combining their structural and compositional information, the gas-particle partitioning behaviors of NACs should be further investigated. The average contributions of total NACs to the light absorption of organic matter at λ = 365 nm (1.10 - 2.57%) in Q f and Q b samples (10.7 - 21.0%) are up to 10 times larger than their mass contributions (Q f 0.31 - 1.01%, Q b 1.08 - 3.31%), so the identified NACs are mostly strong light absorbers. To explain more sample extracts absorption, future research is needed to understand the chemical and optical properties of high molecular weight (e.g., MW > 500 Da) entities in particulate matter.
