Deletion or loss-of-function mutation of LKB1, frequently occurring in non-small cell lung cancers (NSCLCs), is a predominant caution of NSCLC initiation and progression. However, the upstream ...signaling pathways governing LKB1 activation are largely unknown. Here, we report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromises the LKB1/AMPK signaling axis, in turn leading to the elevation of NSCLC cell proliferation, invasion and migration. Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis. Clinically, AURKA displays high levels in NSCLC patients, and correlates with poor outcome of patients with lung adenocarcinoma. Pathologically, the amplification or activation of AURKA-induced impairment of the LKB1/AMPK signaling pathway contributes to NSCLC initiation and progression, highlighting AURKA as a potential therapeutic target for combatting hyperactive AURKA-driven NSCLCs.
Aims
This study investigated the dose‐effect of manganese (Mn) addition on wheat straw (WS) decomposition, and explored the potential mechanisms of Mn involved in the acceleration of WS decomposition ...in regards to the soil microbial communities and enzyme activities.
Methods and Results
A 180‐day incubation experiment was performed to examine the decomposition of WS under four Mn levels, that is, 0, 0.25, 1 and 2 mg g−1. The effects of microbial communities and enzyme activities were evaluated using control (0 mg g−1) and Mn (0.25 mg g−1) treatments. Our results revealed that Mn (0.25 mg g−1) addition significantly increased WS decomposition, and enhanced the release of carbon and nitrogen. Optimal Mn addition (0.25 mg g−1) also caused significant increases in the activity of neutral xylanase (NEX), laccase (Lac), manganese peroxidase (MnP) and lignin peroxidase (LiP) within the incubation period. Mn (0.25 mg g−1) addition also enriched some operational taxonomic units (OTUs) that, in turn, had the potential ability to decompose crop straw, such as secreting lignocellulolytic enzymes.
Conclusions
Mn (0.25 mg g−1) could promote WS decomposition through enrichment of the microbial species involved in biomass decomposition, which enhanced the lignocellulose‐degrading enzyme activity.
Significance and Impact of the Study
This study provides evidence for Mn to promote WS biodegradation after Mn application, opening new windows to improve the utilization efficiency of crop residues.
Energy saving and efficient drying model play important role in the extraction of high quality Chinese medicinal materials. In this work, the gastrodia elata was subjected to hot air drying of ...revealing the drying characteristics with the medicinal indicator of gastrodin ingredient. The multiple drying variables of drying temperature, air velocity, slice thickness and relative humidity were taken into account. Based on the experimental results, an optimized multi-variable model was established to predict the characteristics of drying the sliced gastrodia elata with hot air. The experimental results show that the optimal model of the Page model enables to predict the water loss process of the sliced gastrodia elata under multiple drying variables. The optimal drying variables were determined based on the maximum gastrodin content, of which the temperature was 60 °C, air velocity was 3.5 m/s, slice thickness was 0.4 cm and relative humidity was 25 %. Meanwhile, the drying quality was improved efficiently. The effective diffusion coefficient of gastrodia elata in the hot air drying ranged from 2.254 × 10−9 m2/s to 3.241 × 10−8 m2/s, and the dry activation energy was 34.16 kJ/mol.
•A multi-variable model for the drying behavior of the gastrodia elata with hot air was established.•The effects of drying variables on the characteristics of gastrodia elata were tested and analyzed.•The change of the effective medicinal ingredient of gastrodin in the drying process was revealed.•The optimal drying variables were determined to obtain the maximum gastrodin content.
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
Combined crown and post-and-core treatment often requires multiple intermittent appointments and takes a long time. This article describes a novel method for simultaneously fabricating a custom glass ...fiber post-and-core and the corresponding crown. The critical step, defined as a post-and-core virtual try-in, is to construct a virtual crown abutment that mimics the profile of a real one gained after post-cementation and tooth preparation. The fully digital workflow optimizes the treatment and saves time by accomplishing restorations on the first visit.
The greenhouse gases (GHGs) derived from agriculture include carbon dioxide, nitrous oxide, and methane (CH4). Of these GHGs, CH4, in particular, constitutes a major component of the GHG emitted by ...the agricultural sector. Along with environmental concerns, CH4 emission also leads to losses in gross energy intake with economic implications. While ruminants are considered the main source of CH4 from agriculture, nonruminant animals also contribute substantially, and the CH4 emission intensity of nonruminants remains comparable to that of ruminants. Means of mitigating CH4 emissions from enteric fermentation have therefore been sought. Methane is produced by methanogens—archaeal microorganisms that inhabit the digestive tracts of animals and participate in fermentation processes. As the diversity of methanogen communities is thought to be responsible for the differences in CH4 production among nonruminant animals, it is necessary to investigate the archaeal composition of specific animal species. Methanogens play an important role in energy metabolism and adipose tissue deposition in animals. Higher abundances of methanogens, along with their higher diversity, have been reported to contribute to lean phenotype in pigs. In particular, a greater abundance of Methanosphaera spp. and early dominance of Methanobrevibacter smithii have been reported to correlate with lower body fat formation in pigs. Besides the contribution of methanogens to the metabolic phenotype of their hosts, CH4 release reduces the productivity that could be achieved through other hydrogen (H2) disposal pathways. Enhanced participation of acetogenesis in H2 disposal, leading to acetate formation, could be a more favorable direction for animal production and the environment. Better knowledge and understanding of the archaeal communities of the gastrointestinal tract (GIT), including their metabolism and interactions with other microorganisms, would thus allow the development of new strategies for inhibiting methanogens and shifting toward acetogenesis. There are a variety of approaches to inhibiting methanogens and mitigating methanogenesis in ruminants, which can find an application for nonruminants, such as nutritional changes through supplementation with biologically active compounds and management changes. We summarize the available reports and provide a comprehensive review of methanogens living in the GIT of various nonruminants, such as swine, horses, donkeys, rabbits, and poultry. This review will help in a better understanding of the populations and diversity of methanogens and the implications of their presence in nonruminant animals.
Objective: To evaluate the role of ultrasound in the use and maintenance of ECMO for COVID-19 cases.Methods: During the outbreak of COVID-19 in China, three critically ill patients were treated with ...ECMO in our hospital. Bedside ultrasound was used throughout all procedures, including in the delivery and daily monitoring of ECMO.Results: Structural and functional changes of heart, pleural effusion, as well as thrombus formation in one patient’s right atrium were noted with ultrasonography. Using bedside ultrasound as a troubleshooting tool throughout ECMO therapy provided a lot of useful and reliable real-time information to assist clinical decision making.Conclusion: Ultrasound shall play an important role in the use and maintenance of ECMO for COVID-19 cases.
To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications.
A case series study. A retrospective ...analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed.
Among the 101 patients, 53 were males and 48 were females
aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with
Here, we study structural properties of the supercritical carbon dioxide and discover the existence of persistent medium-range order correlations, which make supercritical carbon dioxide nonuniform ...and heterogeneous on an intermediate length scale. We report on the CO2 heterogeneity shell structure where, in the first shell, both carbon and oxygen atoms experience gas-like-type interactions with short-range order correlations while within the second shell, oxygen atoms essentially exhibit a liquid-like type of interactions due to localization of transverse-like phonon packets. Importantly, we highlight a catalytic role of atoms inside of the nearest-neighbor heterogeneity shell in providing a mechanism for diffusion and proving the existence of an additional thermodynamic boundary in the supercritical carbon dioxide on an intermediate length scale. Finally, we discuss important implications for answering the intriguing question whether Venus may have had CO2 oceans and urge for an experimental detection of this persistent local-order heterogeneity.
Nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) is a transcription factor that binds to the antioxidant response element (ARE) in the upstream promoter region of various ...antioxidant-responsive genes. Hence, at least in nonruminants, the NFE2L2-ARE signaling pathway plays an important role in the cellular antioxidant defense system. Whether oxidative stress in bovine mammary epithelial cells alters NFE2L2 or the NFE2L2-ARE pathway is unclear. Therefore, the objective of this study was to examine the response in NFE2L2- and NFE2L2-ARE-related components in bovine mammary epithelial cells (BMEC) under oxidative stress. An in silico analysis to identify potential phosphorylation sites on NFE2L2 and the protein kinases was performed with Netphos 3.1 (http://www.cbs.dtu.dk/services/NetPhos/) and Scansite (http://scansite.mit.edu) software. Isolated BMEC were exposed to H2O2 (600 μM) for 6 h to induce oxidative stress. In silico analysis revealed ataxia telangiectasia-mutated (ATM) serine/threonine kinase as a key kinase responsible for the phosphorylation of NFE2L2. Thus, after the 6 h incubation with H2O2, BMEC were transiently transfected with ATM-small interfering RNA (siRNA) 1, 2, or 3. Compared with the control, transfection with ATM-siRNA3 resulted in proliferation rates that were 60.7 and 36.2% lower with or without H2O2. In addition, production of reactive oxygen species and malondialdehyde increased markedly, but activities of superoxide dismutase, glutathione peroxidase, catalase, and glutathione-S-transferase decreased markedly in transfected cells without or with H2O2 compared with the control. Transfected cells had markedly lower protein and mRNA expression of NFE2L2 without or with H2O2 compared with the control. In addition, fluorescent activity of the ARE in transfected BMEC indicated that NFE2L2-driven transcriptional activation decreased under oxidative stress. Overall, results indicate that ATM is a physiologically relevant NFE2L2 kinase. Furthermore, inhibition of ATM activity can cause marked alterations in oxidative stress leading to cell death as a result of diminished capacity of BMEC to cope with H2O2-induced cytotoxicity. The relevance of this kinase in vivo merits further study.
PDF
