Nachweis von Arsen in der Asche feuerbestatteter Leichen

Ohne ZusammenfassungMitteilung aus dem Laboratorium für angewandte Chemie der K. Universität München.     

Olfactory Stimulation Successfully Modulates the Neurochemical,Biochemical and Behavioral Phenotypes of the Visceral Pain

Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency.     

Identification of Antiviral Compounds against Monkeypox Virus Profilin-like Protein A42R from Plantago lanceolata

Infections caused by the monkeypox virus (MPXV) have continued to be transmitted significantly in recent years. However, understanding the transmission mechanism, risk factors, and consequences of infection are still limited. Structure-based drug design for MPXV is at an early stage due to the availability of protein structures that have been determined experimentally. However, the structure of the A42R profilin-like protein of MPXV has been solved and submitted to the structure database. This study illustrated an in silico structure-based approach to identify the potential hit compound against A42R of MPXV. Here, 65 Plantago lanceolata compounds were computationally screened against A42R of MPXV. Virtual screening identified top five hits (i) Luteolin 7,3′-Diglucuronide (PubChem ID: 44258091), (ii) Luteolin 7-Glucuronide-3′-Glucoside (PubChem ID: 44258090), (iii) Plantagoside (PubChem ID: 174157), (iv) Narcissoside (PubChem ID: 5481663), and (v) (AlphaE,8S,9R)-N-(3,4-Dihydroxyphenethyl)-8-[(3,4-Dihydroxyphenethyl)Carbamoyl]-9-(1,3-Benzodioxole-5-Yl)-3aalpha,7aalpha-Ethano-1,3-Benzodioxole-5-Acrylamide (PubChem ID: 101131595), with binding energy <−9.0 kcal/mol that was further validated by re-docking and molecular dynamic (MD) simulation. Interaction analysis of re-docked poses confirmed the binding of these top hits to the A42R protein as reported in the reference compound, including active residues ARG114, ARG115, and ARG119. Further, MD simulation and post-simulation analysis support Plantagoside and Narcissoside for substantial stability in the binding pocket of viral protein contributed by hydrogen and hydrophobic interactions. The compounds can be considered for further optimisation and in vitro experimental validation for anti-monkeypox drug development.     

含有杯芳烃的树枝状分子

杯芳烃与树枝状大分子是超分子化学中两类极为重要的主体分子,将这两种主体分子结合在一起所得到的基于杯芳烃的树枝状大分子,不仅仅能够将两者的优点集中到一个分子之中,同时还有可能产生一些新颖的性能,成为新型的智能材料、分子器件或是纳米材料。本文按照杯芳烃的类型,在树枝状大分子中的位置,综述了到目前为止有关这一新型主体分子的研究成果,展望了它在将来的发展。     

Multi-Stream Convolution-Recurrent Neural Networks Based on Attention Mechanism Fusion for Speech Emotion Recognition

The quality of feature extraction plays a significant role in the performance of speech emotion recognition. In order to extract discriminative, affect-salient features from speech signals and then improve the performance of speech emotion recognition, in this paper, a multi-stream convolution-recurrent neural network based on attention mechanism (MSCRNN-A) is proposed. Firstly, a multi-stream sub-branches full convolution network (MSFCN) based on AlexNet is presented to limit the loss of emotional information. In MSFCN, sub-branches are added behind each pooling layer to retain the features of different resolutions, different features from which are fused by adding. Secondly, the MSFCN and Bi-LSTM network are combined to form a hybrid network to extract speech emotion features for the purpose of supplying the temporal structure information of emotional features. Finally, a feature fusion model based on a multi-head attention mechanism is developed to achieve the best fusion features. The proposed method uses an attention mechanism to calculate the contribution degree of different network features, and thereafter realizes the adaptive fusion of different network features by weighting different network features. Aiming to restrain the gradient divergence of the network, different network features and fusion features are connected through shortcut connection to obtain fusion features for recognition. The experimental results on three conventional SER corpora, CASIA, EMODB, and SAVEE, show that our proposed method significantly improves the network recognition performance, with a recognition rate superior to most of the existing state-of-the-art methods.     

A Quassinoid Diterpenoid Eurycomanone from Eurycoma longifolia Jack Exerts Anti-Cancer Effect through Autophagy Inhibition

Eurycomanone (EN) is one of the representative quassinoid diterpenoids from roots of Eurycoma longifolia Jack, a natural medicine that is widely distributed in Southeast Asia. Previous studies showed that EN induces cancer cell apoptosis and exhibits anti-cancer activity, but the molecular mechanism of EN against cancer has still not been elucidated. In this study, we examined the regulatory effect of EN on autophagy to reveal the mechanism of EN-mediated colon cancer growth inhibition. First, we found that EN is able to inhibit colon cancer cell proliferation and colony formation. The angiogenesis level in cancer cells was inhibited as well. Next, the treatment of EN led to the suppression of autophagy, which was characterized by the downregulation of the LC3-II level and the formation of GFP-LC3 puncta under EN treatment in colon cancer. Moreover, we revealed that the mTOR signaling pathway was activated by EN in a time- and concentration-dependent manner. Finally, autophagy induction protected colon cancer cells from EN treatment, suggesting that autophagy improves cell survival. Taken together, our findings revealed the mechanism of EN against colon cancer through inhibiting autophagy and angiogenesis in colon cancer, supporting that the autophagy inhibitor EN could be developed to be a novel anti-cancer agent.     

Dystrophin Protein Quantification as a Duchenne Muscular Dystrophy Diagnostic Biomarker in Dried Blood Spots Using Multiple Reaction Monitoring Tandem Mass Spectrometry: A Preliminary Study

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle loss, leading to difficulties in movement. Mutations in the DMD gene that code for the protein dystrophin are responsible for the development of DMD disorder, where the synthesis of this protein is completely halted. Therefore, circulating dystrophin protein could be a promising biomarker of DMD disease. Current methods for diagnosing DMD have sensitivity, specificity, and reproducibility limitations. Herein, a quantitative liquid chromatography–tandem spectrometry (LC–MS/MS) technique in multiple reaction monitoring (MRM) mode was designed and validated for accurate dystrophin protein measurement in a dried blood spot (DBS). The method was successfully validated on the basis of international guidelines regarding calibration curves, precision, and accuracy. In addition, patients and healthy controls were used to test the amount of dystrophin protein circulating in DBS samples as a potential biomarker for DMD disorders. DMD patients were found to have considerably lower levels than controls. To the best of our knowledge, this is the first study to report dystrophin levels in DBS through LC–MS/MS as a diagnostic marker for DMD to the proposed MRM method, providing a highly specific and sensitive approach to dystrophin quantification in a DBS that can be applied in DMD screening.     

Biomimetic surface preparation of inert polymer films via grafting long monoalkyl chain phosphatidylcholine

To explore construction of novel mimicking biomembrane on biomaterials surfaces,a new polymerizable phosphatidylcholine containing a long monoalkyl chain ended with acryl group(AASOPC) was designed and synthesized, which was easily derived from the terminal amino group of 9-(2-amino-ethylcarbamoyl)-nonyl-1-phosphatidyl-choline (ASOPC) reacting with acryloyl chloride.The obtained AASOPC was grafted on poly(ethylene terephthalate)(PET) via surface-initiated atom-transfer radical polymerization(SI-ATRP) to form mimicking biomembrane.These modified surface structures of PET were investigated using water contact angle(WAC),X-ray photoelectron spectroscopy(XPS) and atomic force microscopy(AFM).The results indicated that the new mimicking phosphatidylcholine biomembrane could be prepared on inert polymer surfaces by using the acryloyl phosphatidylcholine(AASOPC) via surface-initiated atom transfer radical polymerization(SI-ATRP).