Potential analgesic effect of Foshousan oil-loaded chitosan-alginate nanoparticles on the treatment of migraine

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine.Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug.Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group.Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine

New insights into the BiB 3 O 6 melt structure3

The structure of borate melt has long been a fundamental unsolved problem in condensed matter physics, materials chemistry. Here, we use high temperature Raman spectroscopy and first principles calculations to study the structural change before and after the melting of a BiB 3 O 6 crystal to obtain the BiB 3 O 6 melt structure. A transformation of the 4-fold coordinated boron atoms to 3-fold coordinated boron atoms and a destruction of the atomic configuration around the Bi 3+ ions were found when the crystal melted. Considering the growth habit of the BIBO crystal, we proposed a polymer model for the first time to describe the melt structure

Circular RNAs in extracellular vesicles: Promising candidate biomarkers for schizophrenia

As one of common and severe mental illnesses, schizophrenia is difficult to be diagnosed exactly. Both its pathogenesis and the causes of its development are still uncertain because of its etiology complexity. At present, the diagnosis of schizophrenia is mainly based on the patient’s symptoms and signs, lacking reliable biomarkers that can be used for diagnosis. Circular RNAs in extracellular vesicles (EV circRNAs) can be used as promising candidate biomarkers for schizophrenia and other diseases, for they are not only high stability and disease specificity, but also are rich in contents and easy to be detected. The review is to focus on the research progress of the correlation between circRNAs and schizophrenia, and then to explores the possibility of EV circRNAs as new biomarkers for the schizophrenia diagnosis

Elevated atmospheric CO2 concentration triggers redistribution of nitrogen to promote tillering in rice

Elevated atmospheric CO2 concentration (eCO2) often reduces nitrogen (N) content in rice plants and stimulates tillering. However, there is a general consensus that reduced N would constrain rice tillering. To resolve this contradiction, we investigated N distribution and transcriptomic changes in different rice plant organs after subjecting them to eCO2 and different N application rates. Our results showed that eCO2 significantly promoted rice tillers (by 0.6, 1.1, 1.7, and 2.1 tillers/plant at 0, 75, 150, and 225 kg N ha−1 N application rates, respectively) and more tillers were produced under higher N application rates, confirming that N availability constrained tillering in the early stages of growth. Although N content declined in the leaves (−11.0 to −20.7 mg g−1) and sheaths (−9.8 to −28.8 mg g−1) of rice plants exposed to eCO2, the N content of newly emerged tillers on plants exposed to eCO2 equaled or exceeded the N content of tillers produced under ambient CO2 conditions. Apparently, the redistribution of N within the plant per se was a critical adaptation strategy to the eCO2 condition. Transcriptomic analysis revealed that eCO2 induced less extensive alteration of gene expression than did N application. Most importantly, the expression levels of multiple N-related transporters and receptors such as nitrate transporter NRT2.3a/b and NRT1.1a/b were differentially regulated in leaf and shoot apical meristem, suggesting that multiple genes were involved in sensing the N signal and transporting N metabolites to adapt to eCO2. The redistribution of N in different organs could be a universal adaptation strategy of terrestrial plants to eCO2

NF-κB Induced the Donor Liver Cold Preservation Related Acute Lung Injury in Rat Liver Transplantation Model

We have observed at our clinical work that acute lung injury (ALI) often occurs in patients transplanted with donor livers persevered for long time. So, we conducted this study to investigate the influence of cold preservation time (CPT) of donor liver on ALI induced by liver transplantation (LT), and further study the role of nuclear factor-κB (NF-κB) in the process.Wistar rats were used as donors and recipients to establish orthotopic rat liver transplantation models. Donor livers were preserved at 4°C for different lengths of time. The effect of NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC), on ALI was detected. All samples were harvested after 3 h reperfusion. The severity of liver injury was evaluated first. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue and liver outflow serum were measured respectively. The severity indexes of ALI, the activity of NF-κB and inhibitor-κBα (I-κBα) in lung/liver were measured accordingly.With the prolonged liver CPT, the liver damage associated indexes and ALI-related indexes all increased significantly. TNF-α and IL-1β in liver outflow serum increased accordingly, and the activity of NF-κB in liver/lung increased correspondingly. All these ALI-associated indexes could be partially reversed by the use of PDTC.Extended CPT aggravates the damage of donor liver and induces the expressions of TNF-α and IL-1β in liver. These inflammatory factors migrate to lung via liver outflow blood and activate NF-κB in lung, inducing ALI finally. NF-κB may play a critical role in LT-related ALI. Patients with or at risk of ALI may benefit from acute anti-inflammatory treatment with PDTC

Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy

BackgroundNon-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge.MethodsWe performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas® EGFR Mutation Test v2 (Cobas) examinations.ResultsOf the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment.ConclusionOur results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib

Pleiotropic effects of the wheat domestication gene Q on yield and grain morphology

Transformation from q to Q during wheat domestication functioned outside the boundary of threshability to increase yield, grains m−2, grain weight and roundness, but to reduce grains per spike/spikelet. Mutation of the Q gene, well-known affecting wheat spike structure, represents a key domestication step in the formation of today’s free-threshing, economically important wheats. In a previous study, multiple yield components and spike characteristics were associated with the Q gene interval in the bread wheat ‘Forno’ × European spelt ‘Oberkulmer’ recombinant inbred line population. Here, we reported that this interval was also associated with grain yield, grains m−2, grain morphology, and spike dry weight at anthesis. To clarify the roles of Q in agronomic trait performance, a functional marker for the Q gene was developed. Analysis of allelic effects showed that the bread wheat Q allele conferred free-threshing habit, soft glumes, and short and compact spikes compared with q. In addition, the Q allele contributed to higher grain yield, more grains m−2, and higher thousand grain weight, whereas q contributed to more grains per spike/spikelet likely resulting from increased preanthesis spike growth. For grain morphology, the Q allele was associated with reduced ratio of grain length to height, indicating a rounder grain. These results are supported by analysis of four Q mutant lines in the Chinese Spring background. Therefore, the transition from q to Q during wheat domestication had profound effects on grain yield and grain shape evolution as well, being a consequence of pleiotropy

Modeling, Simulation and Analysis of Intermediate Fixed Piezoelectric Energy Harvester

To address the problem that piezoelectric energy harvesters are difficult to apply in certain environments, this paper establishes the theoretical study of the intermediate fixed disc piezoelectric energy harvester (IFDPEH) based on the unimorph under concentrated force. The reliability of the model was indirectly verified by numerical simulation and Computer-Aided Engineering (CAE) simulation. The effects of load, radius ratio (piezoelectric layer/intermediate support), thickness ratio (piezoelectric layer/total thickness), and elastic modulus ratio (substrate/piezoelectric layer) on electrical energy were studied. The results indicate that the radius/thickness ratios of the IFDPEH based on aluminum and beryllium bronze are 0.05/0.31 and 0.05/0.48, respectively. In addition, through parameter comparison, it is found that the most important parameters affecting IFDPEH power are radius ratio and large load. The results are demonstrated to be meaningful for broadening the application of piezoelectric energy harvesters by the derived closed-form equations for the electrical energy along the diameters of the piezoelectric discs in the z-direction