Segawa syndrome caused by TH gene mutation and its mechanism

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (TH) gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. To explore the clinical manifestations and possible pathogenesis of the disease, we analyzed the clinical data of seven patients. Next-generation sequencing showed that the TH gene mutation in three children was a reported homozygous mutation (c.698G>A). At the same time, two new mutations of the TH gene were found in other children: c.316_317insCGT, and c.832G>A (p.Ala278Thr). We collected venous blood from four patients with Segawa syndrome and their parents for real-time quantitative polymerase chain reaction analysis of TH gene expression. We predicted the structure and function of proteins on the missense mutation iterative thread assembly refinement (I-TASSER) server and studied the conservation of protein mutation sites. Combined with molecular biology experiments and related literature analysis, the qPCR results of two patients showed that the expression of the TH gene was lower than that in 10 normal controls, and the expression of the TH gene of one mother was lower than the average expression level. We speculated that mutation in the TH gene may clinically manifest by affecting the production of dopamine and catecholamine downstream, which enriches the gene pool of Segawa syndrome. At the same time, the application of levodopa is helpful to the study, diagnosis and treatment of Segawa syndrome

Research on Management Conflict Matrix of Cross-border E-commerce Logistics Based on TRIZ Model

Cross-border E-commerce and international logistics are national key projects. International logistics is more important as Cross-border E-commerce becomes the main form of international trade. Based on the features of Cross-border E-commerce logistics, this paper selects Guangdong, where developing factors of Cross-border E-commerce industry and international logistics industry are relatively complete, as the representative research site. Questionnaires are distributed to 503 researchers from Cross-border E-commerce companies and universities in Guangdong province. Researchers use SPSS to analyze the reliability and validity of the data, and adopt the TRIZ theory to construct a logistics conflict matrix. The positive factor is inversely proportional to the negative factor variable. On the one hand, the ideal state of logistics weakens as the negative factor of logistics increases; on the other hand, the ideal state of logistics strengthens as the positive factor of logistics increases

Characterizing Post-Fire Forest Structure Recovery in the Great Xing’an Mountain Using GEDI and Time Series Landsat Data

Understanding post-fire forest recovery is critical to the study of forest carbon dynamics. Many previous studies have used multispectral imagery to estimate post-fire recovery, yet post-fire forest structural development has rarely been evaluated in the Great Xing’an Mountain. In this study, we extracted the historical fire events from 1987 to 2019 based on a classification of Landsat imagery and assessed post-fire forest structure for these burned patches using Global Ecosystem Dynamics Investigation (GEDI)-derived metrics from 2019 to 2021. Two drivers were assessed for the influence on post-fire structure recovery, these being pre-fire canopy cover (i.e., dense forest and open forest) and burn severity levels (i.e., low, moderate, and high). We used these burnt patches to establish a 25-year chronosequence of forest structural succession by a space-for-time substitution method. Our result showed that the structural indices suggested delayed recovery following the fire, indicating a successional process from the decomposition of residual structures to the regeneration of new tree species in the post-fire forest. Across the past 25-years, the dense forest tends toward greater recovery than open forest, and the recovery rate was faster for low severity, followed by moderate severity and high severity. Specifically, in the recovery trajectory, the recovery indices were 21.7% and 17.4% for dense forest and open forest, and were 27.1%, 25.8%, and 25.4% for low, moderate, and high burn severity, respectively. Additionally, a different response to the fire was found in the canopy structure and height structure since total canopy cover (TCC) and plant area index (PAI) recovered faster than relative height (i.e., RH75 and RH95). Our results provide valuable information on forest structural restoration status, that can be used to support the formulation of post-fire forest management strategies in Great Xing’an Mountain

Antitumor activity of isosteroidal alkaloids from the plants in the genus Veratrum and Fritillaria

Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of isosteroidal alkaloids include antihypertensive, antitussive, anti-inflammatory, antithrombosis, among others. Recently, some studies show that this kind of alkaloids exhibited significant antitumor activity. To the best of our knowledge, there is no review focusing on their antitumor activity and mechanism of their antitumor activity. To fill the gap, in this review, we summarized antitumor effects of the isosteroidal alkaloids from genus Veratrum and Fritillaria on different tumors and the mechanisms of their antitumor activity. In conclusion, this kind of alkaloids has extensive antitumor activity, and there are several main mechanisms of their antitumor activity, including the Hedgehog signaling pathway, caspase-3 dependent apoptosis, cell cycle, and autophagy

Translation and validation of chinese version of MDASI immunotherapy for early-phase trials module: a cross-sectional study

Abstract Background During immunotherapy treatment and survival, identifying symptoms requires a standardized and validated assessment tool. The aim of this study was to translate, validate and use the Chinese version of the Immunotherapy of the M.D. Anderson Symptom Inventory for Early-Phase Trials module (MDASI-Immunotherapy EPT) to assess the symptom burden of cancer patients receiving immunotherapy in China. Methods The MDASI-Immunotherapy EPT was translated into Chinese using Brislin’s translation model and the back-translation method. In total, 312 Chinese-speaking colorectal cancer patients receiving immunotherapy were enrolled in the trial from August 2021 to July 2022 after receiving definitive diagnoses in our cancer center. The reliability and validity of the translated version was evaluated. Results Cronbach’s α values were 0.964 and 0.935 for the symptom severity and interference scales, respectively. Significant correlations were found between the MDASI-Immunotherapy EPT-C and FACT-G scores (-0.617–0.732, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by ECOG PS (all P < 0.01). The overall mean subscale scores for the core and interference subscales were 1.92 ± 1.75 and 1.46 ± 1.87, respectively. Fatigue, numbness/tingling, and disturbed sleep had the highest scores for the most serious symptoms. Conclusion The MDASI-Immunotherapy EPT-C showed adequate reliability and validity for measuring symptoms among Chinese-speaking colorectal cancer patients receiving immunotherapy. The tool could be used in clinical practice and clinical trials to gather patients’ health and quality of life data and manage their symptoms in a timely manner in the future

Optimization of Extraction and Enrichment of Steroidal Alkaloids from Bulbs of Cultivated Fritillaria cirrhosa

The bulbs of cultivated Fritillaria cirrhosa (BCFC) are used in China both for food and folk medicine due to its powerful biological activities. The aim of this study is to optimize the extraction and enrichment conditions of alkaloids from BCFC. Firstly, the orthogonal experimental design was used to optimize and evaluate four variables (ethanol concentration, solid-liquid ratio, extraction time, and temperature). Thereafter, resin adsorption was as a means to enrich alkaloids. Among 16 tested resins, H-103 resin presented higher adsorption capacity and desorption ratio. The equilibrium experimental data of the adsorption of total alkaloids, imperialine, and peimisine were well-fitted to the pseudo-first-order kinetics model, Langmuir and Freundlich isotherms models. Finally, in order to optimize the parameters for purifying alkaloids, dynamic adsorption and desorption tests were carried out. After one run treatment with H-103 resin, the contents of total alkaloids, imperialine, and peimisine in the product were 21.40-, 18.31-, and 22.88-fold increased with recovery yields of 94.43%, 90.57%, and 96.16%, respectively

End-to-End Optimization for a Compact Optical Neural Network Based on Nanostructured 2 &#x00D7; 2 Optical Processors

Recent research in silicon photonic chips has made huge progress in optical computing owing to their high speed, small footprint, and low energy consumption. Here, we employ nanostructured 2 &#x00D7; 2 optical processors in an optical neural network for implementing a binary classification task efficiently. The proposed optical neural network is composed of five linear layers including ten optical processors in each layer, and nonlinear activation functions. 2 &#x00D7; 2 optical processors are designed based on digitized meta-structures which have an extremely compact footprint of 1.6 &#x00D7; 4 &#x03BC;m2. A brand-new end-to-end design strategy based on Deep Q-Network is proposed to optimize the optical neural network for classifying a generated ring data set with better generalization, robustness, and operability. A high-efficient transfer matrix multiplication method is applied to simplify the calculation process in traditional optical software. Our numerical results illustrate that the maximum and mean accuracy on the testing data set can reach 90.5&#x0025; and 87.8&#x0025;, respectively. The demonstrated optical processors with a significantly compact area, and the efficient optimization method exhibit high potential for large-scale integration of whole-passive optical neural network on a photonic chip

LC&ndash;MS/MS Coupled with Chemometric Analysis as an Approach for the Differentiation of Fritillariae cirrhosae Bulbus and Fritillariae pallidiflorae Bulbus

Fritillariae cirrhosae bulbus (FCB) is one of the most important traditional Chinese medicines (TCM) for the treatment of cough and phlegm. Due to increasing demand and the complexity of FCB&rsquo;s botanical origin, various substitutes have appeared in the market, resulting in a major challenge to distinguish FCB and its substitutes (F. pallidiflorae bulbus, FPB). Therefore, discriminating FCB from FPB has becoming an urgent necessity. In this study, an ultra-high-performance liquid chromatography&ndash;electrospray ionization&ndash;tandem mass spectrometry (UPLC&ndash;ESI&ndash;MS/MS) method was developed for the simultaneous quantification of nine steroidal alkaloids (imperialine-3-&beta;-D-glucoside, imperialine, verticine, verticinone, peimisine, yibeinoside A, delavine, delavinone, ebeidinone) within 8 min. According to the composition and content of the above nine compounds, multivariate chemometric analyses were applied for the classification of FCB and FPB. The quantitative results showed that there were both similarities and differences in the content of nine steroidal alkaloids between FCB and FPB, and it was difficult to directly distinguish these two species. Fortunately, with the aid of chemometric analyses, FCB and FPB were successfully differentiated by partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA) models based on the nine alkaloids&rsquo; content. Moreover, four compounds (yibeinoside A, ebeiedinone, delavinone and imperialine) were discovered as potential markers for the identification and differentiation of FCB and FPB. Additionally, compared to other studies, this work collected a large number of samples (49 batches of FCB and 17 batches of FPB) to ensure the reliability of the results. In conclusion, this work established a new approach for the authentication of FCB based on its active components, which provides a good reference for the quality control of FCB and will help us to understand the chemical composition differences between FCB and its adulterants further