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Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy. [Display omitted] • TREM2 deficiency promotes tumor progression in murine glioblastoma (GBM) models • TREM2 downregulation is observed in individual GBM-infiltrated myeloid cells • AAV-mediated TREM2 overexpression represses GBM growth and synergizes with ICB • Lipidic damage signals causes a TREM2-mediated protective response in CNS cancers Zhong et al. show that TREM2 plays an immunoprotective role prompted by central nervous system-enriched sphingolipids during glioblastoma (GBM) progression. Single-cell and spatial sequencing revealed TREM2 downregulation in GBM-infiltrating myeloid cells. TREM2 overexpression represses GBM and synergizes with anti-PD-1 therapy. This study highlights organ-specific remodeling of myeloid cell targets in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both humans and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques. Methods: In this study, we explore the use of fluorescence micro‐optical sectioning tomography (fMOST) and single‐cell RNA sequencing (scRNA‐seq) to map the spatial and cellular distribution of a representative neurotropic virus, rabies virus (RABV), in the whole brain. Mice were inoculated with a lethal dose of a recombinant RABV encoding enhanced green fluorescent protein (EGFP) under different infection routes, and a three‐dimensional (3D) view of RABV distribution in the whole mouse brain was obtained using fMOST. Meanwhile, we pinpointed the cellular distribution of RABV by utilizing scRNA‐seq. Results: Our fMOST data provided the 3D view of a neurotropic virus in the whole mouse brain, which indicated that the spatial distribution of RABV in the brain was influenced by the infection route. Interestingly, we provided evidence that RABV could infect multiple nuclei related to fear independent of different infection routes. More surprisingly, our scRNA‐seq data revealed that besides neurons RABV could infect macrophages and the infiltrating macrophages played at least three different antiviral roles during RABV infection. Conclusion: This study draws a comprehensively spatial and cellular map of typical neurotropic virus infection in the mouse brain, providing a novel and insightful strategy to investigate the pathogenesis of RABV and other neurotropic viruses. [ABSTRACT FROM AUTHOR]

Background: Ribosome profiling has been widely used for studies of translation under a large variety of cellular and physiological contexts. Many of these studies have greatly benefitted from a series of data-mining tools designed for dissection of the translatome from different aspects. However, as the studies of translation advance quickly, the current toolbox still falls in short, and more specialized tools are in urgent need for deeper and more efficient mining of the important and new features of the translation landscapes. Results: Here, we present RiboMiner, a bioinformatics toolset for mining of multi-dimensional features of the translatome with ribosome profiling data. RiboMiner performs extensive quality assessment of the data and integrates a spectrum of tools for various metagene analyses of the ribosome footprints and for detailed analyses of multiple features related to translation regulation. Visualizations of all the results are available. Many of these analyses have not been provided by previous methods. RiboMiner is highly flexible, as the pipeline could be easily adapted and customized for different scopes and targets of the studies. Conclusions: Applications of RiboMiner on two published datasets did not only reproduced the main results reported before, but also generated novel insights into the translation regulation processes. Therefore, being complementary to the current tools, RiboMiner could be a valuable resource for dissections of the translation landscapes and the translation regulations by mining the ribosome profiling data more comprehensively and with higher resolution. RiboMiner is freely available at https://github.com/xryanglab/RiboMiner and https://pypi.org/project/RiboMiner. [ABSTRACT FROM AUTHOR]

A simple and accurate method coupling high-performance liquid chromatography–evaporative light scattering detector was developed to simultaneously quantify the five triterpenoids in different parts of Aralia elata (Miq.) Seem (A. elata). for the first time. Samples were extracted using 70% methanol by ultrasonication. Separation of the analytes was performed on a Welchrom C18 column with acetonitrile and water as the mobile phase. All calibration curves had good linearity over relatively wide range of concentrations. This method showed good average recovery and precision, also high sensitivity with limits of detection and quantification. This method was successfully applied to quantify triterpenoid saponins in 14 samples collected from different areas of China. This study demonstrate that there is significant variation in the amounts of the five triterpenoids of interest in A. elata. Furthermore, 70% methanol extracts of roots had the strongest effect on ox-low-density lipoprotein-induced human umbilical vein endothelial cell apoptosis. [ABSTRACT FROM AUTHOR]

A simple and sensitive analysis using ultra high performance liquid chromatography with a tandem mass spectrometric system operated in selected reaction monitoring mode was developed for the determination of 11 phenolic acids, atractyloside, and carboxyatractyloside in rat plasma. The two classes of analytes were then separated on a Waters ACQUITY™ UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase of 0.2% formic acid in water containing 10 mM ammonium acetate and methanol. Detection was accomplished by selected reaction monitoring scanning via an electrospray source operating in negative ionization mode. The calibration curve was linear (R2 = 0.990) over a concentration range of 1.20–3500 ng/mL, while the validated lower limit of quantification was 1.20 ng/mL. The precision varied from 0.84 to 4.62%, and the accuracy varied within ±5%. The method proved robust with sample freezing and thawing and with short‐ and long‐term sample storage. The established method was used for simultaneous quantification and was successfully used for the first time for the pharmacokinetic evaluation of 13 compounds after the intragastric administration of raw and processed Fructus Xanthii in rats. The results indicated that processing affects the absorption and metabolism of Fructus Xanthii extract. Importantly, the results also indicated the importance of processing for the clinical application of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Phenolic acids are important active components of certain Traditional Chinese Medicines (TCM) and have a wide range of biological effects. Separation and purification of phenolic acids remains challenging due to difficulties with quality control using existing chromatographic methods The purpose of this study was to compare the effects of different chromatographic columns and conditions for the separation of phenolic acids. The BEH column was determined to be optimal, providing efficient separation in the shortest time (17.00 min) using gradient elution with carbon dioxide as the mobile phase, methanol/acetonitrile (70:30, v/v) with 1% TFA as the modifier, and a flow rate of 0.8 mL/min. Good peak shapes were obtained, and the peak asymmetry values were close to 1.00 for all phenolic acids. The resolution was more than 2.83 for all separated peaks. The developed method was subsequently applied to the determination of phenolic acids in Xanthii Fructus . These results are beneficial for quality control and standardization of herbal drugs using UPC 2 , providing an efficient, rapid and environmentally friendly scientific basis for future analysis of phenolic acids. [ABSTRACT FROM AUTHOR]

Abstract As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in 30 batches of raw and processed Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common peaks were detected and eight compounds of caffeoylquinic acids were simultaneously quantified in RXF and PXF. All the analytes were detected with satisfactory linearity (R2 > 0.9991) over wide concentration ranges. Simultaneously, the chemically latent information was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that there were significant differences between RXF and PXF from different regions in terms of the content of eight caffeoylquinic acids. Potential chemical markers for XF were found during processing by chemometrics [ABSTRACT FROM AUTHOR]

In view of the dynamic phenomenon that coal and rock are susceptible to external impact disturbance in the mining process, combined with the rheological hypothesis mechanism of coal and gas outburst, the RLSS-II-type triaxial loading creep test system of gas-containing coal and rock developed by ourselves is used to carry out the conventional triaxial rheological test of gas-containing coal and rock and the rheological disturbance effect test of gas-containing coal and rock under impact disturbance. The strength limit neighborhood of gas-containing coal and rock is determined, and the gas-containing coal and rock entering the strength limit neighborhood are subjected to different impact disturbances. The experimental results show that, (1) under the confining pressure of 0 MPa, 2.5 MPa, and 5 MPa, the longitudinal deformations of gas-bearing coal and rock are 32 mm, 27 mm, and 22 mm, respectively, indicating that the deformation of coal and rock will be affected by confining pressure, and with the increase of confining pressure, the deformation will decrease. (2) In the test, the deformation of coal and rock in the late stage of uniform creep stage can be regarded as a strain threshold. Before this threshold, the strain of coal and rock is not obvious, and the deformation is only 1.1 mm. After exceeding a threshold, the deformation of coal and rock is 9 mm, and the deformation increases significantly. Then, it enters the accelerated creep stage quickly and finally damages. The vicinity of this threshold is called the strength limit neighborhood of coal and rock containing gas. (3) The gas-bearing coal and rock without entering the strength limit neighborhood and entering the strength limit neighborhood are changed by confining pressure and different impact disturbance, respectively. It is found that, whether in the strength limit neighborhood or outside the strength limit neighborhood, the confining pressure has an effect on the strain, but the influence is not large. Under different impact disturbance, the deformation of coal and rock within and outside the strength limit neighborhood is 8 mm and 0.4 mm, respectively, and the deformation changes obviously, indicating that the impact disturbance has a great influence on the deformation of coal and rock within the strength limit neighborhood, and the coal and rock with large impact disturbance are destroyed before the coal and rock with small impact disturbance, indicating that the greater the impact disturbance, the shorter the time required for destruction. [ABSTRACT FROM AUTHOR]

1. The aim of this study was to develop a selective, rapid, accurate and sensitive ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for pharmacokinetic (PK) studies of phytoecdysones and triterpenoid saponins after oral administration of five monomers, crude, wine-processed and salt-processed Radix Achyranthis bidentatae (RAB). 2. A Thermo Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 μm) coupled with a mobile phase of (A) acetonitrile and (B) water (both containing 0.3% acetic acid) was used for sample separation. The mass analysis was performed in a triple quadruple mass spectrometer using selected reaction monitoring (SRM) with negative scan mode. 3. The results showed that this method exhibited desirable sensitivity, precision, stability and repeatability. The extraction recoveries of the compounds ranged from 94.2 to 99.8% and the matrix effects ranged from 93.3 to 100.5%. Comparing the Cmax and AUC of five analytes in those groups showed this tendency: salt-processed RAB > wine-processed RAB > crude RAB > monomer group. The results confirmed the feasibility of TCM theory to enhance the efficacy of processed RAB. [ABSTRACT FROM AUTHOR]

In the study, a surface plasmon resonance-based (SPR-based) competitive assay was performed to analyze different compounds' inhibitory activity to TNF-α, an important pro-inflammatory cytokine in the pathogenesis of chronic inflammatory diseases. Moreover, the single mass spectrometry (MS) detection method was coupled with an ultra-high-performance liquid chromatography (UPLC) system for the routine quality control (QC) of a traditional Chinese medicine (TCM). The above quality control strategy was evaluated with Lonicera japonica Thunb. Analytes were firstly separated on a Waters ACQUITYTM UPLC HSS T3 column (2.1 × 50 mm; particle size = 1.8 μm) using a 0.1% formic acid gradient elution, then detected by negative ESI mass spectrometry. The limits of quantification (LOQ) for analytes reached 0.005–0.56 μg/mL. The LOD of the QDa detector was lower than that of the PDA detector, indicating its wider detection range. The QDa detector was also more suitable for the analysis of the complex matrix of TCM. The method showed excellent linearity, with regression coefficients higher than 0.9991. The average recoveries of the investigated analytes were in the range of 98.78–105.13%, with an RSD below 3.91%. The inter-day precision range (n = 3 days) was 2.51–4.54%. Compared to other detectors, this strategy could be widely applied in the quantitative analysis of TCM. In addition, the chemically latent data could be revealed using chemometric analysis. Importantly, this study provides an efficient screening method for small-molecule inhibitors targeting the TNF-α pathway. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) can be used to guide breast cancer surgery with breast conservation for large tumors with a substantially reduced size after neoadjuvant chemotherapy (NAC).Purpose: To evaluate the value of dynamic contrast-enhanced MRI (DCE-MRI) for measuring residual tumor size and enhancement patterns following preoperative NAC.Material and Methods: Eighty-nine patients with breast cancer underwent breast DCE-MRI; 38 patients (39 lesions) were treated with NAC and examined for residual disease following therapy. Two patients were excluded because surgery had been performed >2 weeks after the final MR examination. Thus, we correlated the DCE-MRI results of 36 patients (37 lesions) with postoperative histopathological findings. Residual disease was confirmed by more enhancement compared to normal glandular tissue at the initial tumor site. Residual tumor size on DCE-MRI was compared with postoperative pathology findings. Tumor enhancement patterns on DCE-MRI were analyzed and correlated with pathological classification.Results: MRI revealed 34 cases of residual tumors, with two false positives and one false negative. Pathological and MR measurements were correlated (r = 0.793). The correlation of mass enhancement size (r = 0.87, n = 14) with pathology and DCE-MRI was higher than for non-mass-like enhancement (NME) (r = 0.735, n = 23). The distribution of pathologic classification was significantly different between different MRI enhancement patterns (P = 0.006). Mass enhancement had higher cellularity than NME.Conclusion: MRI is useful for evaluating residual carcinoma following NAC. Mass enhancement with higher cellularity after NAC can be evaluated more accurately, which is suitable for evaluating lumpectomy. However, other approaches are required for NME, which has lower cellularity. [ABSTRACT FROM AUTHOR]

eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/− mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health. • eIF3—via eIF3e—promotes mRNA selective early translation elongation • eIF3e-dependent mRNAs encode membrane, secretory, and organelle targeted proteins • eIF3 travels with 80S ribosomes until nascent chains emerge for subcellular targeting • In vivo , eIF3e promotes mitochondrial function and skeletal muscle health Lin et al. discovered that, in addition to its function in canonical translation initiation, multi-subunit eIF3 migrates with post-initiation 80S ribosomes to promote early translation elongation of mRNAs encoding organellar, secretory, and membrane-targeted proteins. Loss of eIF3's elongation and subcellular targeting activity leads to mitochondrial and skeletal muscle dysfunction. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a rapid, reliable, and sensitive ultra-performance liquid chromatography with triple-quadrupole tandem mass spectrometry coupled with chemometric method to measure and evaluate the differences between thirteen compounds in raw and processed Tussilago farfara L. from different sources. This assay method was validated, and the results indicated that the calibration curves for the thirteen compounds had good linearity (R2 > 0.9990). The limits of detection and limits of quantification of the thirteen compounds ranged from 0.0012 to 0.0095 μg/mL and from 0.0038 to 0.0316 μg/mL, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions and stability ranged from 1.06 to 2.00%, 0.26 to 1.99%, and 0.75 to 1.97%, respectively. The sample recovery rates of the thirteen compounds with different concentrations were 94.47–104.06%. The chemometric results, including principal component analysis, hierarchical clustering analysis, three-dimensional analysis, and box plot analysis, indicated that there are significance differences in raw and processed Tussilago farfara L. The results of this study confirm that the proposed method is the first reported method that has been successfully applied for simultaneous determination and discovery of the difference between thirteen compounds of raw and processed Tussilago farfara L. Thus, this method could be a helpful tool for the detection and confirmation of the quality of traditional Chinese medicines and provide a basis for future pharmacological studies. [ABSTRACT FROM AUTHOR]

An accurate and reliable method using ultra-high performance liquid chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC–MS/MS) was established for simultaneous quantification of five major bioactive analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae (RAB). The results showed that this method exhibited desirable sensitivity, precision, stability, and repeatability. The overall intra-day and inter-day variations (RSD) were in the range of 1.57–2.46 and 1.51–3.00%, respectively. The overall recoveries were 98.58–101.48% with a relative standard deviation (RSD) of 0.01–1.86%. In addition, the developed approach was applied to 21 batches of raw, wine-processed, and salt-processed samples of RAB. Hierarchical clustering analysis (HCA), principal component analysis (PCA), heat map, and boxplot analysis were performed to evaluate the quality of raw, wine-processed, and salt-processed RAB collected from different regions. The chemometrics combined with the quantitative analysis based on UHPLC–MS/MS results indicated that the content of five analytes increased significantly in processed RAB compared to raw RAB. [ABSTRACT FROM AUTHOR]