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Abstract Glioma is the most prevalent brain tumor, presenting with limited treatment options, while patients with malignant glioma and glioblastoma (GBM) have poor prognoses. The physical obstacle to drug delivery imposed by the blood‒brain barrier (BBB) and glioma stem cells (GSCs), which are widely recognized as crucial elements contributing to the unsatisfactory clinical outcomes. In this study, we found a small molecule, gambogic amide (GA-amide), exhibited the ability to effectively penetrate the blood-brain barrier (BBB) and displayed a notable enrichment within the tumor region. Moreover, GA-amide exhibited significant efficacy in inhibiting tumor growth across various in vivo glioma models, encompassing transgenic and primary patient-derived xenograft (PDX) models. We further performed a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout screen to determine the druggable target of GA-amide. By the combination of the cellular thermal shift assay (CETSA), the drug affinity responsive target stability (DARTS) approach, molecular docking simulation and surface plasmon resonance (SPR) analysis, WD repeat domain 1 (WDR1) was identified as the direct binding target of GA-amide. Through direct interaction with WDR1, GA-amide promoted the formation of a complex involving WDR1, MYH9 and Cofilin, which accelerate the depolymerization of F-actin to inhibit the invasion of patient-derived glioma cells (PDCs) and induce PDC apoptosis via the mitochondrial apoptotic pathway. In conclusion, our study not only identified GA-amide as an effective and safe agent for treating glioma but also shed light on the underlying mechanisms of GA-amide from the perspective of cytoskeletal homeostasis.

Amongst the robotics and autonomous systems, robot manipulators have proven themselves to be of increasing importance and are widely adopted to substitute for human in repetitive and/or hazardous tasks. In this paper, the purpose is to research on dynamic performance and motion control of robot manipulator for the more precise, crucial and critical tasks in industry. Firstly, the forward and inverse kinematics was accurately described by obtaining the link transformation matrices from each joint in robot manipulator. To find admissible solutions along the path, the workspace of the manipulator was determined by joint limit condition and validated by actual measurement. And then, the dynamic performance of robot manipulator is researched by using the forming flexible multi-body system. Furthermore, the frequency response curves are obtained by exciting vibration simulation based on vibration model, which the predicted method was validated by comparing simulation and experimental results. Finally, the control system architecture was given and the grasping process was conducted by gripper based on motion trajectory control in the workspace. [ABSTRACT FROM AUTHOR]

Electrowetting is a widely used and effective method to tune the wettability of ionic liquids at solid-liquid interfaces, but it usually requires an external electric field. Here, we proposed a strategy for conveniently tuning ionic liquid wettability by adopting ferroelectric LiNbO3 single crystals as functional substrates. A heating pretreatment process was applied to modulate the surface charge characteristics of LiNbO3 substrates, leading to an improved wettability of [EMIM][BF4] and [EMIM][NTf2] on the LiNbO3 substrates with both positively poled (+Z) and negatively poled (−Z) surfaces. This work may be of great interest in the field of ferroelectric-based microelectronics.

Asymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featured in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.