ABSTRACT
Primary ciliary dyskinesia (PCD) is a group of genetically heterogeneous disorders characterized by clinical manifestations resulting from abnormal ciliary motility. Mutations in critical genes, such as Cyclin O (CCNO), have been associated with severe respiratory disease, though limited data are currently available. Here we show that CCNO deficient ciliated cells can only form a reduced number of fully functional centrioles that can mature into ciliated basal bodies, and their transport and anchoring to the top of the plasma membrane are abnormal. Furthermore, we observed that CCNO localizes not only in the cytoplasm but also in the nucleus during the early stages of ciliogenesis, and this dual localization persists into adulthood. Transcriptome analysis revealed downregulation of genes involved in cilia assembly and movement, along with altered transcription factors associated with ciliation upon CCNO depletion. These findings indicate that CCNO may serve as a key regulator in the transcriptional regulation of multiciliogenesis.
ABSTRACT
Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation. It has been demonstrated that many types of ion channels including K+ channels, Ca2+ permeable channels, and Na+ channels exist in vascular smooth muscle cells and endothelial cells, contributing to the regulation of vascular homeostasis and vasomotor function. An increasing number of studies suggested that the structural and functional alterations of ion channels located in arteries contribute to vascular hyporesponsiveness during shock, but the underlying mechanisms remained to be fully clarified. Therefore, the expression and functional changes in ion channels in arteries associated with shock are reviewed, to pave the way for further exploring the potential of ion channel-targeted compounds in treating refractory hypotension in shock.
Subject(s)
Ion Channels , Shock , Humans , Shock/physiopathology , Shock/metabolism , Animals , Ion Channels/metabolism , Vasoconstriction/physiology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiopathology , Vasodilation/physiology , Hypotension/physiopathology , Hypotension/metabolismABSTRACT
In this paper, the solid-state shear milling (S3M) strategy featuring a very strong three-dimensional shear stress field was adopted to prepare the high-performance polyoxymethylene (POM)/molybdenum disulfide (MoS2) functional nanocomposite. The transmission electron microscope and Raman measurement results confirmed that the bulk MoS2 particle was successfully exfoliated into few-layer MoS2 nanoplatelets by the above simple S3M physical method. The polarized optical microscope (PLM) observation indicated the pan-milled nanoscale MoS2 particles presented a better dispersion performance in the POM matrix. The results of the tribological test indicated that the incorporation of MoS2 could substantially improve the wear resistance performance of POM. Moreover, the pan-milled exfoliated MoS2 nanosheets could further substantially decrease the friction coefficient of POM. Scanning electron microscope observations on the worn scar revealed the tribological mechanism of the POM/MoS2 nanocomposite prepared by solid-state shear milling. The tensile test results showed that the pan-milled POM/MoS2 nanocomposite has much higher elongation at break than the conventionally melt-compounded material. The solid-state shear milling strategy shows a promising prospect in the preparation of functional nanocomposite with excellent comprehensive performance at a large scale.
ABSTRACT
Previously a ring finger protein 20 (RNF20) is found to be essential for meiotic recombination and mediates H2B ubiquitination during spermatogenesis. However, its role in meiotic division is still unknown. Here, it is shown that RNF20 is localized at both centromeres and spindle poles, and it is required for oocyte acentrosomal spindle organization and female fertility. RNF20-depleted oocytes exhibit severely abnormal spindle and chromosome misalignment caused by defective bipolar organization. Notably, it is found that the function of RNF20 in spindle assembly is not dependent on its E3 ligase activity. Instead, RNF20 regulates spindle assembly by recruiting tropomyosin3 (TPM3) to both centromeres and spindle poles with its coiled-coil motif. The RNF20-TPM3 interaction is essential for acentrosomal meiotic spindle assembly. Together, the studies uncover a novel function for RNF20 in mediating TPM3 recruitment to both centromeres and spindle poles during oocyte spindle assembly.
Subject(s)
Meiosis , Spindle Apparatus , Male , Female , Humans , Spindle Apparatus/metabolism , Oocytes/metabolism , Spindle Poles/metabolism , CentromereABSTRACT
Electromagnetic interference shielding (EMI SE) modules are the core component of modern electronics. However, the traditional metal-based SE modules always take up indispensable three-dimensional space inside electronics, posing a major obstacle to the integration of electronics. The innovation of integrating 3D-printed conformal shielding (c-SE) modules with packaging materials onto core electronics offers infinite possibilities to satisfy ideal SE function without occupying additional space. Herein, the 3D printable carbon-based inks with various proportions of graphene and carbon nanotube nanoparticles are well-formulated by manipulating their rheological peculiarity. Accordingly, the free-constructed architectures with arbitrarily-customized structure and multifunctionality are created via 3D printing. In particular, the SE performance of 3D-printed frame is up to 61.4 dB, simultaneously accompanied with an ultralight architecture of 0.076 g cm-3 and a superhigh specific shielding of 802.4 dB cm3 g-1. Moreover, as a proof-of-concept, the 3D-printed c-SE module is in situ integrated into core electronics, successfully replacing the traditional metal-based module to afford multiple functions for electromagnetic compatibility and thermal dissipation. Thus, this scientific innovation completely makes up the blank for assembling carbon-based c-SE modules and sheds a brilliant light on developing the next generation of high-performance shielding materials with arbitrarily-customized structure for integrated electronics.