Search

ObjectiveTo find a method to distinguish exogenous gamma-hydroxybutyrate （GHB） from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry （UPLC-MS） based on exosome for quantitative detection of GHB in the rat blood.MethodsAdult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone （GBL） intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected.ResultsThe concentration of GHB in the control group was （87.36±33.48） ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was （110 400.00±1 766.35） ng/mL, （1 479.00±687.01） ng/mL and （133.60±12.17） ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were （91.47±33.44） ng/mL and （49.43±7.05） ng/mL, respectively.ConclusionGHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

This article introduces a novel six‐axis parallel manipulator co‐driven by motors with and without geared reducers. The design leverages the high stiffness provided by the geared motors and the high force‐sensing capability of the direct drives. When the geared motors move synchronously with their direct‐drive counterparts, the manipulator mimics a Delta robot's spatial translation, while the direct drives double as high‐performance force sensors. An asymmetric design of the manipulator is proposed to allocate a larger portion of torque to the geared motors, raising the overall stiffness of the mechanism. Relations between the external force to the driving torque are derived and the torque redistribution effect of the asymmetric design is illustrated numerically. Experimental results on prototypes of both the symmetric design and the asymmetric design show that direct drives consistently exhibit much higher linearity in the force‐to‐torque relationship compared to the geared drives, and also confirm that asymmetric design alleviates the torque burden on the direct drives. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

The mechanism of methamphetamine toxicity and addiction is the key research direction of forensic toxicology, and the development of omics technology provides a new platform for further study of this direction. METH toxic damage and addiction are reflected differently in genes, ribonucleic acid （RNA） transcription, protein and metabolism. This article summarizes the achievements and shortcomings of multi-omics technologies such as genome, transcriptome, metabolome and proteome in the study of METH damage and addiction, and discusses the strategies and advantages of multi-omics combined analysis in the study of METH toxic damage and addiction mechanism，in order to provide more useful reference information for forensic toxicology of METH.

ObjectiveTo study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine （METH） and its possible mechanism in neurotoxicity.MethodsThe rats were intraperitoneally injected with METH （15 mg/kg） every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.ResultsA total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor （PPAR）, adenosine 5’-monophosphate-activated protein kinase （AMPK） and other signaling pathways were significantly changed.ConclusionMETH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.

Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome （SARS）, Middle East respiratory syndrome （MERS） and corona virus disease 2019 （COVID-19）. Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people’s health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient： it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.

Objective To establish an analysis method for simultaneous determination of 13 sedative substances and their metabolites in blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry （LC-MS/MS） technology and to apply the method to actual cases. Methods The samples were extracted with ethyl acetate after an internal standard was added. The extract was condensed until it was nearly dry and then its residues were dissolved with methanol, filtered through 0.22 μm filter and finally determined. The 13 sedative substances and their metabolites were separated through the C18 chromatographic column, then gradient elution was performed on them with methanol and 20 mmol/L ammonium formate （containing 0.1% formic acid） solution. After that, they were determined in the electrospray positive ion mode and quantified by internal standard method. Results The 13 sedative substances and their metabolites in blood showed good linearity in the range of 5-200 μg/L with correlation coefficients ranging from 0.990 3 to 0.999 8. The detection limits were 0.1-1.0 μg/L. Recovery rates of sedative substances were in the range of 71.2%-93.4% when solutions with concentrations of 10, 50 and 200 μg/L were added. The deviations of intra-day and inter-day relative standard deviations （RSD） were not more than 8.6%. Accuracies （bias） were within ±9.8%. Conclusion This method is rapid, simple, effective and sensitive, and can be applied to analysis of 13 sedative substances and their metabolites in blood in forensic toxicology.

This study presents the major features of extreme spring cold spells (ESCS) in North China during 1961–2014 and the evolving processes. During an ESCS, northern Eurasia is controlled by large-scale positive SLP anomalies and an anomalous anticyclone that continuously transport northern cold air to North China, causing significant, persistent, lower-than-normal daily temperatures. In fact, these positive SLP and anticyclonic wind anomalies begin to appear over northwestern Europe about 10 days prior to the ESCS. The anticyclonic wind anomalies keep moving southeastward and expand to the west of Lake Baikal until two days before the ESCS. Then, the center of the anomalous low-level anticyclone moves over Lake Baikal, inducing northerly wind anomalies that transport cold air into North China. In the following days, as the positive SLP anomalies weaken, the anomalous anticyclone and related northerly winds appear to wane, and the ESCS gradually comes to an end. The results may prove meaningful for the prediction and early warning of ESCSs.

There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases. [ABSTRACT FROM AUTHOR]

Byline: Wei-Long. Zhong, Hui-Jun. Wang, Zhi-Miao. Lin, Yong. Yang Sir, Dyschromatosis universalis hereditaria is a group of congenital pigmentary disorders characterized by generalized mottled hypopigmented and hyperpigmented macules.[1] It clinically [...]