Notes

Laryngeal Physical Symptoms within Spasmodic Dysphonia.
Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network. It is found that the peak time of GCs migration (P7-10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network.Dimension reduction is a challenging problem in complex dynamical systems. Here, a dimension reduction approach of landscape (DRL) for complex dynamical systems is proposed, by mapping a high-dimensional system on a low-dimensional energy landscape. The DRL approach is applied to three biological networks, which validates that new reduced dimensions preserve the major information of stability and transition of original high-dimensional systems. The consistency of barrier heights calculated from the low-dimensional landscape and transition actions calculated from the high-dimensional system further shows that the landscape after dimension reduction can quantify the global stability of the system. The epithelial-mesenchymal transition (EMT) and abnormal metabolism are two hallmarks of cancer. With the DRL approach, a quadrastable landscape for metabolism-EMT network is identified, including epithelial (E), abnormal metabolic (A), hybrid E/M (H), and mesenchymal (M) cell states. The quantified energy landscape and kinetic transition paths suggest that for the EMT process, the cells at E state need to first change their metabolism, then enter the M state. The work proposes a general framework for the dimension reduction of a stochastic dynamical system, and advances the mechanistic understanding of the underlying relationship between EMT and cellular metabolism.Protein arginine methyltransferase 5 (PRMT5) is the type II arginine methyltransferase that catalyzes the mono- and symmetrical dimethylation of protein substrates at the arginine residues. Emerging evidence reveals that PRMT5 is involved in the regulation of tumor cell proliferation and cancer development. However, the exact role of PRMT5 in human lung cancer cell proliferation and the underlying molecular mechanism remain largely elusive. Here, it is shown that PRMT5 promotes lung cancer cell proliferation through the Smad7-STAT3 axis. Depletion or inhibition of PRMT5 dramatically dampens STAT3 activation and thus suppresses the proliferation of human lung cancer cells. Furthermore, depletion of Smad7 blocks PRMT5-mediated STAT3 activation. Mechanistically, PRMT5 binds to and methylates Smad7 on Arg-57, enhances Smad7 binding to IL-6 co-receptor gp130, and consequently ensures robust STAT3 activation. The findings position PRMT5 as a critical regulator of STAT3 activation, and suggest it as a potential therapeutic target for the treatment of human lung cancer.Nanomedicines with photodynamic therapy and reactive oxygen species (ROS)-triggered drug release capabilities are promising for cancer therapy. However, most of the nanomedicines based on ROS-responsive nanocarriers still suffer from serious ROS consumption during the triggered drug release process. Herein, a photodynamic-chemodynamic cascade strategy for the design of drug delivery nanosystem is proposed. A doxorubicin hydrochloride-loaded ROS-responsive polymersome (DOX-RPS) is prepared via the self-assembly of amphiphilic poly(ethylene glycol)-poly(linoleic acid) and poly(ethylene glycol)-(2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-α)-iron chelate (PEG-HPPH-Fe). The RPS can effectively deliver a drug to tumor site through passive targeting effect. Upon laser irradiation, the photosensitizer HPPH can efficiently generate ROS, which further causes in situ oxidation of linoleic acid chain and subsequent RPS structural destruction, permitting triggered drug release. Intriguingly, catalyzed by HPPH-Fe, ROS will be regenerated from linoleic acid peroxide through a chemodynamic process. Therefore, ROS-triggered drug release can be achieved without ROS over-consumption. The in vitro and in vivo results confirmed ROS generation, triggered drug release behavior, and potent antitumor effect of the DOX-RPS. This photodynamic-chemodynamic cascade strategy provides a promising approach for enhanced combination therapy.As membrane-bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low-pH treatment caused increased uptake efficiency and retained cell-type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self-aggregation-based mechanism for the enhanced homologous uptake. Furthermore, these low-pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near-infrared irradiance-triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor.Neurological diseases are a prevalent cause of global mortality and are of growing concern when considering an ageing global population. Traditional treatments are accompanied by serious side effects including repeated treatment sessions, invasive surgeries, or infections. For example, in the case of deep brain stimulation, large, stiff, and battery powered neural probes recruit thousands of neurons with each pulse, and can invoke a vigorous immune response. This paper presents challenges in engineering and neuroscience in developing miniaturized and biointegrated alternatives, in the form of microelectrode probes. Progress in design and topology of neural implants has shifted the goal post toward highly specific recording and stimulation, targeting small groups of neurons and reducing the foreign body response with biomimetic design principles. Implantable device design recommendations, fabrication techniques, and clinical evaluation of the impact flexible, integrated probes will have on the treatment of neurological disorders are provided in this report. The choice of biocompatible material dictates fabrication techniques as novel methods reduce the complexity of manufacture. Wireless power, the final hurdle to truly implantable neural interfaces, is discussed. These aspects are the driving force behind continued research significant breakthroughs in any one of these areas will revolutionize the treatment of neurological disorders.Graphene oxide (GO), which has many oxygen functional groups, is a promising candidate for use in moisture-responsive sensors and actuators due to the strong water-GO interaction and the ultrafast transport of water molecules within the stacked GO sheets. In the last 5 years, moisture-responsive actuators based on GO have shown distinct advantages over other stimuli-responsive materials and devices. Particularly, inspired by nature organisms, various moisture-enabled soft robots have been successfully developed via rational assembly of the GO-based actuators. Herein, the milestones in the development of moisture-responsive soft robots based on GO are summarized. In addition, the working mechanisms, design principles, current achievement, and prospects are also comprehensively reviewed. In particular, the GO-based soft robots are at the forefront of the advancement of automatable smart devices.2D layered materials turn out to be the most attractive hotspot in materials for their unique physical and chemical properties. A special class of 2D layered material refers to materials exhibiting phase transition based on environment variables. Among these materials, transition metal dichalcogenides (TMDs) act as a promising alternative for their unique combination of atomic-scale thickness, direct bandgap, significant spin-orbit coupling and prominent electronic and mechanical properties, enabling them to be applied for fundamental studies as catalyst materials. Metal phosphorous trichalcogenides (MPTs), as another potential catalytic 2D phase transition material, have been employed for their unusual intercalation behavior and electrochemical properties, which act as a secondary electrode in lithium batteries. The preparation of 2D TMD and MPT materials has been extensively conducted by engineering their intrinsic structures at the atomic scale. In this study, advanced synthesis methods of preparing 2D TMD and MPT materials are tested, and their properties are investigated, with stress placed on their phase transition. The surge of this type of report is associated with water-splitting catalysis and other catalytic purposes. This study aims to be a guideline to explore the mentioned 2D TMD and MPT materials for their catalytic applications.As a novel noninvasive therapeutic modality combining low-intensity ultrasound and sonosensitizers, sonodynamic therapy (SDT) is promising for clinical translation due to its high tissue-penetrating capability to treat deeper lesions intractable by photodynamic therapy (PDT), which suffers from the major limitation of low tissue penetration depth of light. The effectiveness and feasibility of SDT are regarded to rely on not only the development of stable and flexible SDT apparatus, but also the screening of sonosensitizers with good specificity and safety. To give an outlook of the development of SDT equipment, the key technologies are discussed according to five aspects including ultrasonic dose settings, sonosensitizer screening, tumor positioning, temperature monitoring, and reactive oxygen species (ROS) detection. In addition, some state-of-the-art SDT multifunctional equipment integrating diagnosis and treatment for accurate SDT are introduced. Further, an overview of the development of sonosensitizers is provided from small molecular sensitizers to nano/microenhanced sensitizers. Several types of nanomaterial-augmented SDT are in discussion, including porphyrin-based nanomaterials, porphyrin-like nanomaterials, inorganic nanomaterials, and organic-inorganic hybrid nanomaterials with different strategies to improve SDT therapeutic efficacy. There is no doubt that the rapid development and clinical translation of sonodynamic therapy will be promoted by advanced equipment, smart nanomaterial-based sonosensitizer, and multidisciplinary collaboration.
Homepage: