Telmisartan, one unique angiotensin II type 1 receptor blocker, has been attracting attention due to its putative peroxisome proliferator-activated receptor (PPAR)-γ or β/δ actions. Recently, ...telmisartan has been reported to exert neuroprotective effects in animal models of Parkinson's disease (PD). However, the underlying mechanisms have not been fully clarified. Recently, accumulating evidence has shown that endoplasmic reticulum (ER) stress plays a crucial role in rotenone-induced neuronal apoptosis. Additionally, studies have revealed that inositol-requiring enzyme/endonuclease 1α (IRE1α) is necessary and sufficient to trigger ER stress. In the present study, we aimed to determine whether ER stress-activated IRE1α-mediated apoptotic pathway is involved in the neuroprotection of telmisartan in the rotenone rats of PD and explore the possible involvement of PPAR-β/δ activation. The catalepsy tests were performed to test the catalepsy symptom. The dopamine content and α-synuclein expression were ascertained through high-performance liquid chromatography and immunohistochemistry, respectively. The expression of IRE1α, TNF receptor associated factor 2 (TRAF2), caspase-12 and PPAR-β/δ was detected by western blot. Neuronal apoptosis was assessed by TUNEL and immunohistochemistry. Our results show that telmisartan ameliorated the catalepsy symptom and attenuated dopamine depletion as well as α-synuclein accumulation. Moreover, telmisartan decreased ER stress-mediated neuronal apoptosis. Furthermore, telmisartan inhibited IRE1α-TRAF2-caspase-12 apoptotic signaling pathway. Additionally, telmisartan activated PPAR β/δ, implying that PPAR-β/δ activation properties of telmisartan are possibly or partially involved in the neuroprotective effects. In conclusion, our findings suggest that suppressing ER stress-activated IRE1α-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rats of PD.
The hospital ward's environment directly impacts the health and well-being of its occupants, especially patients. This study investigated the impacts of environmental factors (thermal, acoustic, ...luminous, and IAQ) and self-described health conditions on subjective environmental perception and satisfaction in hospital wards. A winter field survey of 156 occupants (patients and visitors) was conducted in a large general hospital in Changsha, China, using a combination of environment measurements, questionnaires, and interviews. The results showed comprehensive effects of environmental factors on occupants' perceptions. Lower air temperature improved participants' assessment of the acoustic environment; lower noise environment led to a positive assessment of IAQ perception; lower CO2 concentration improved the assessment of the thermal environment in a hotter environment. Acoustic perception (13.4 %), IAQ perception (10.5 %), and luminous perception (8.2 %) were significantly affected by health conditions. Moreover, the poorer the health condition, the lower the environmental satisfaction rating, and the acceptable environmental thresholds differed for individuals with various health conditions. The "very weak" group scored 1.6 and 1.5 points lower than the "very fit" for each environmental factor and overall satisfaction, respectively. For IEQ control in healthcare facilities, it is necessary to fully consider patients' health conditions during hospitalization and create a better recuperation environment for vulnerable groups.
•The crossed effects of environmental factors on environmental perceptions in hospital wards were demonstrated.•The health condition significantly affected occupants' environmental perception and satisfaction.•Environmental factors that have the greatest impact on overall satisfaction in hospital wards were identified.•The IEQ satisfaction model indicator for hospital wards was established.
The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among ...hyperuricemia, gout, HF, and all-cause mortality.
The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001-2018 and 2007-2018 were included in this study. The binary logistic regression, Kaplan-Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality.
Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality.
Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.
Minicomposite, as the elementary scale of the full-scale ceramic matrix composites (CMCs), has been commonly considered as the appropriate specimen type for basic research on environmental behavior ...of CMCs due to its simple structure, low fabrication cost and mature modeling foundation. However, its size is too small relative to the full-scale CMCs, resulting in the existing environmental performance testing equipment developed for macrocomposites not matching it in all respects. In order to fill this gap, a compact environmental performance testing apparatus, which consists mainly of a two-zone furnace, gas humidifier, control system and a pair of quartz tubes and high temperature specimen grips, has been designed and built here. Creep test of SiC fiber at elevated temperatures from 800 to 1100 °C with water vapor and oxidation test of SiC/SiC minicomposite at 1316 °C in stress-free wet oxygen environment were carried out respectively to verify the accuracy and reliability of the rig. With the apparatus, the environmental degradation mechanism of CMCs can be quantitatively analyzed, which lays a foundation for the service life prediction and environmental performance optimization of CMCs.
The immunoinhibitory effect of glucocorticoid and immunoenhancing attributes of melatonin (MEL) are well known, however, the involvement of glucocorticoid receptor (GR) in melatonin modulation of ...bacterial toxins caused-inflammation has not been studied in colon. Pyocyanin (PCN), a toxin released by Pseudomonas aeruginosa, can destroy cells through generating superoxide products and inflammatory response. Here we report that PCN treatment elevated the generation of reactive oxygen species (ROS), which further lead to mitochondrial swelling and caspase cascades activation both in vivo and in vitro. However, MEL treatment alleviated the oxidative stress caused by PCN on cells through scavenging ROS and restoring the expression of antioxidant enzyme so that to effectively alleviate the apoptosis. Large amounts of ROS can activate the NLRP3 signaling pathway, so MEL inhibited PCN induced NLRP3 inflammasome activation and inflammatory cytokines (IL-1β, IL-8, and TNF-α) secretion. In order to further investigate the molecular mechanism, goblet cells were exposed to MEL and PCN in the presence of luzindole and RU486, inhibitors of MEL receptors and GR respectively. It was found that PCN significantly inhibited the expression level of GR, and MEL effectively alleviated the inhibition phenomenon. Moreover, we found that MEL mainly upregulated the expression of GR to achieve its anti-inflammatory and anti-apoptotic functions rather than through its own receptor (MT2) in colon goblet cells. Therefore, MEL can reverse the inhibitory effects of PCN on GR/p-GR expression to present its anti-oxidative and anti-apoptotic function.
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•Glucocorticoid receptors are the vital targets of bacterial toxins pyocyanin in colon.•Melatonin presented anti-apoptotic effects mainly through glucocorticoid receptors.•Glucocorticoid receptors were involved in melatonin inhibiting the activation of NLRP3 inflammasome induced by pyocyanin.
Electron-transport-layer free perovskite solar cells (ETL-free PSCs) have attracted great attention due to their low cost and simple manufacturing process. However, an additional interface layer has ...to be introduced, and the currently achieved efficiency remains far from full-structure PSCs. Here, we report an in situ interface engineering strategy by the methylammonium acetate (MAAc) ionic liquid perovskite precursor. We found that a dipole layer was in situ constructed through the physical adsorption of the residual MAAc polar molecules on the indium tin oxide electrode, which is significantly different from the treatment by the interface layer in previous reports. This allows a decrease of the effective work function and enables in situ band bending in the perovskite semiconductor. The in situ band bending facilitates charge collection and hinders interfacial charge recombination, leading to ETL-free PSCs with a maximum power conversion efficiency of 21.08%, which is the highest report to date.
Abstract Mitigating pre-harvest sprouting (PHS) and post-harvest food loss (PHFL) is essential for enhancing food securrity. To reduce food loss, the use of plant derived specialized metabolites can ...represent a good approach to develop a more eco-friendly agriculture. Here, we have discovered that soybean seeds hidden underground during winter by Tscherskia triton and Apodemus agrarius during winter possess a higher concentration of volatile organic compounds (VOCs) compared to those remaining exposed in fields. This selection by rodents suggests that among the identified volatiles, 3-FurAldehyde (Fur) and (E)-2-Heptenal (eHep) effectively inhibit the growth of plant pathogens such as Aspergillus flavus, Alternaria alternata, Fusarium solani and Pseudomonas syringae . Additionally, compounds such as Camphene (Cam), 3-FurAldehyde, and (E)-2-Heptenal, suppress the germination of seeds in crops including soybean, rice, maize, and wheat. Importantly, some of these VOCs also prevent rice seeds from pre-harvest sprouting. Consequently, our findings offer straightforward and practical approaches to seed protection and the reduction of PHS and PHFL, indicating potential new pathways for breeding, and reducing both PHS and pesticide usage in agriculture.
We investigated the small fatigue crack behavior of alloy GH4169 by using single-edge-notch tension specimens. Residual stress introduced by machining process was taken into consideration, and two ...stress levels were selected. A comparison was made between the experimental results of specimens with and without machining-induced residual stress. The results indicated that fatigue cracks of the two types of specimens initiated from surface inclusions or grain boundaries. For both types of specimens, small cracks grew very slowly when the crack lengths were less than 500 μm. The small crack growth might decelerate and retard temporarily for the existence of grain boundaries. The residual stress effect on crack growth can be identified at σ
max
= 380 MPa, i.e., compressive residual stress might impede the crack growth. However, this phenomenon was indistinguishable at σ
max
= 410 MPa.
EEG-based emotion classification is a vital aspect of human–machine interfaces. However, inter-subject variability poses a challenge for accurate domain-agnostic EEG emotion recognition, often ...requiring individual model calibration with a robust base model for fine-tuning. To overcome this limitation and develop a generalized model, we propose a Generalized Model based on Mutual Information for EEG Emotion Recognition without Adversarial Training (MI-EEG). The MI-EEG model leverages disentanglement to extract shared features, wherein it separates EEG features into domain-invariant class-relevant features and other features. To avoid adversarial training, mutual information minimization is applied during the decoupling process. Additionally, mutual information maximization is used to enrich the features by strengthening the relationship between domain-invariant class-relevant features and emotion labels. Furthermore, the transformer-based feature extractor, which utilizes a multi-headed attention mechanism and pooling operations, enhances the feature quality in the time dimension. The experimental evaluation on two emotional EEG datasets demonstrates the superior performance of the proposed EEG-MI model compared to existing state-of-the-art methods.
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•Mutual information up bound minimization makes Fre and Fir separated.•Mutual information lower bound maximization makes Fre and Fg more relevant.•The Multi-head attention neural network makes the model more robust.
Recently, an increasing number of studies sequence multiple biopsies of primary tumors, and even paired metastatic tumors to understand heterogeneity and the evolutionary trajectory of cancer ...progression. Although several algorithms are available to infer the phylogeny, most tools rely on accurate measurements of mutation allele frequencies from deep sequencing, which is often hard to achieve for clinical samples (especially FFPE samples). In this study, we present a novel and easy-to-use method, PTI (Phylogenetic Tree Inference), which use an iterative top-down approach to infer the phylogenetic tree structure of multiple tumor biopsies from same patient using just the presence or absence of somatic mutations without their allele frequencies. Therefore PTI can be used in a wide range of cases even when allele frequency data is not available. Comparison with existing state-of-the-art methods, such as LICHeE, Treeomics, and BAMSE, shows that PTI achieves similar or slightly better performance within a short run time. Moreover, this method is generally applicable to infer phylogeny for any other data sets (such as epigenetics) with a similar zero and one feature-by-sample matrix.
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