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Accurate localization of central nervous system (CNS) drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI matrix. Herein, we developed a highly efficient sample preparation technique, laser-assisted chemical transfer (LACT), to enhance the detection sensitivity of CNS drugs in brain tissues. A focused diode laser source transilluminated the tissue slide coated with α -cyano-4-hydroxycinnamic acid, an optimal matrix to highly absorb the laser radiation at 405 nm, and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass slide. Subsequently, MALDI MSI was performed on the chemical film without additional sample treatment. One major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein components. The superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse brain. Furthermore, the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h period. Also, the brain-to-plasma (B/P) ratio could be obtained according to MALDI MSI results, providing an alternative means to assess brain penetration in drug discovery. A laser-assisted chemical transfer (LACT) technique has been developed for MALDI MS imaging of CNS drug distribution in brain tissue. [Display omitted] [ABSTRACT FROM AUTHOR]

Motor vehicle exhaust emission has become an important source of global atmospheric emissions, and the urgency of protection and management of this issues has become increasingly prominent. The cooperative control strategy of road vehicles can comprehensively manage the individual vehicles from the whole perspective, which is a powerful means to achieve the goal of dual carbon goal. In the preliminary stage of the IoV, limited communication bandwidth increases the difficulty of designing the above cooperative cruise control scheme. To solve this problem, we designed a new novel periodic intermittent cruise controller to track and assess the real-time operating status and relevant environmental indicators of road vehicles. Compared with the previous continuous controller, the proposed controller subdivides the time domain into each sub-period, and the controller is activated merely during the working time interval of each period, which can effectively reduce the control cost. Besides, when the leading vehicle state changes, the following vehicle can quickly respond to the above adjustment and track the leading vehicles with the new desired speed and headway, thereby reduce the duration time and amplitude of road vehicle state oscillation. Based on the Lyapunov-like function method, the sufficient condition for the existence of designed periodically intermittent cruise controller is given, which guarantees that the closed-loop error dynamic system is satisfies exponential stable, and the controller gain coefficients in proposed control protocol can be obtained via solving a set of linear matrix inequalities with some commercial software built-in toolbox. At last, based on the VT-Microenvironment experiment evaluation model, we have carried out some numerical simulation experiments, and the results show that the periodic intermittent cruise control protocol is feasible in improving vehicle safety tracking performance, and remain valid in reducing energy consumption and exhaust emissions such as CO, HC, NOx, and approximately decreased by 2.52%, 6.65%, 34.75%, and 15.70% respectively from the rural value. This research result provides a technical reference to road traffic safety and environmental assessment. [ABSTRACT FROM AUTHOR]

A cheap and magnetic Ni/Cu/Al/Fe catalyst for the selective hydrogenation of LA into GVL catalysts was prepared by sol-gel method. The reaction pathway was systematically studied by examining the reaction conditions, such as reaction pressure, catalyst loadings, water content, and reaction temperature. Higher reaction pressure and catalyst loadings were prior to form HA, then MHV, finally GVL; ML was easily to form with a higher reaction temperature. Water, as a key role, which was in favor to form HA, then MHV, finally GVL; more important, a higher LA conversion could be obtained in methanol as the solvent with some certain content of water. And, it can give a reference for future new clean energy vehicles' application. [ABSTRACT FROM AUTHOR]

Cutaneous T cell lymphoma (CTCL) is characterized by the accumulation of malignant T cells in the skin. However, advanced CTCL pathophysiology remains elusive and therapeutic options are limited due to the high intratumoral heterogeneity and complicated tumor microenvironment (TME). By comparing the single-cell RNA-seq (scRNA-seq) data from advanced CTCL patients and healthy controls (HCs), we showed that CTCL had a higher enrichment of T/NK and myeloid cells. Subpopulations of T cells (CXCR3+, GNLY+, CREM+, and MKI67+ T cells), with high proliferation, stemness, and copy number variation (CNV) levels, contribute to the malignancy of CTCL. Besides, CCL13+ monocytes/macrophages and LAMP3+ cDC cells were enriched and mediated the immunosuppression via inhibitory interactions with malignant T cells, such as CD47-SIRPA, MIF-CD74, and CCR1-CCL18. Notably, elevated expressions of S100A9 and its receptor TLR4, as well as the activation of downstream toll-like receptor and NF-κB pathway were observed in both malignant cells and myeloid cells in CTCL. Cell co-culture experiments further confirmed that the interaction between malignant CTCL cells and macrophages contributed to tumor growth via S100A9 upregulation and NF-kb activation. Our results showed that blocking the S100A9-TLR4 interaction using tasquinimod could inactivate the NF-κB pathway and inhibit the growth of CTCL tumor cells, and trigger cell apoptosis. Collectively, our study revealed a landscape of immunosuppressive TME mediated by interactions between malignant T cells and myeloid cells, and provided novel targets and potential treatment strategies for advanced CTCL patients. [ABSTRACT FROM AUTHOR]

Abstract: Phenotypic similarity is correlated with a number of measures of gene function, such as relatedness at the level of direct protein–protein interaction. The phenotypic effect of a deleted or mutated gene, which is one part of gene annotation, has caught broad attention. However, there have been few measures to study phenotypic similarity with the data from Human Phenotype Ontology (HPO) database, therefore more analogous measures should be developed and investigated. We used five semantic similarity-based measures (Jiang and Conrath, Lin, Schlicker, Yu and Wu) to calculate the human phenotypic similarity between genes (PSG) with data from HPO database, and evaluated their accuracy with information of protein–protein interaction, protein complex, protein family, gene function or DNA sequence. Compared with the gene pairs that were random selected, the results of these methods were statistically significant (all P<0.001). Furthermore, we assessed the performance of these five measures by receiver operating characteristic (ROC) curve analysis, and found that most of them performed better than the previous methods. This work had proved that these measures based on semantic similarity for calculation of PSG were effective for hierarchical structure data. Our study contributes to the development and optimization of novel algorithms of PSG calculation and provides more alternative methods to researchers as well as tools and directions for PSG study. [Copyright &y& Elsevier]