Opening Of Ion Channels Research Articles

Interfacial oxygen bridges engineering between Nb2O5 and graphene towards advanced sodium ion capacitors.

Nb2O5 has become a focus of research for its suitability as an anode material in sodium ion capacitors (SICs), due to its open ionic channels. The integration of Nb2O5 with reduced graphene oxide (rGO) is known to boost its electrical conductivity. However, the sluggish interfacial charge transfer kinetics and interface collapse of Nb2O5/rGO pose challenges to its rate capability and durability. In this study, oxygen bridges (C-O-Nb bonds) are deliberately incorporated to study how their densities affect the electrochemical characteristics of Nb2O5/rGO. Initially, H2O2 is applied as the functional additive to realize in-situ grafting of oxygen functional groups on graphene oxide (GO), which is referred as GO-H. And GO-H matrix serves as a space confiner to transform the crystallization of Nb2O5 from larger microflower structures to smaller nanocrystals. The resulting Nb2O5/rGO with high oxygen bridges (named as Nb2O5/rGO-H) exhibits a substantial proportion of C-O-Nb bonds (47%), which enhances the charge transfer from rGO to Nb2O5, along with the stabilization of the interface. This leads to the high specific capacity (301.7mAhg-1 at 0.05Ag-1), commendable rate capability (98.0mAhg-1 at 10Ag-1), and exceptional durability (91.1%mAhg-1 capacity retention after 2000 cycles). Moreover, a SIC device fabricated with Nb2O5/rGO-H and active carbon (AC) demonstrates an impressive energy density of 149.6Whkg-1 (at 200Wkg-1). This investigation underscores the pivotal role of interfacial oxygen bridges in optimizing the charge transfer dynamics and stability of nanoscale energy storage materials.

Haloperidol, a typical antipsychotic, inhibits 5-HT3 receptormediated currents in NCB-20 cells: a whole-cell patch-clamp study.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT)3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (Emax) and an increase in EC50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

Unveiling crystal orientation-dependent interface property in composite cathodes for solid-state batteries by in situ microscopic probe

A critical bottleneck toward all-solid-state batteries lies in how the solid(electrode)-solid(electrolyte) interface is fabricated and maintained over repeated cycles. Conventional composite cathodes, with crystallographically distinct electrode/electrolyte interfaces of random particles, create complexities with varying (electro)chemical compatibilities. To address this, we employ an epitaxial model system where the crystal orientations of cathode and solid electrolyte are precisely controlled, and probe the interfaces in real-time during co-sintering by in situ electron microscopy. The interfacial reaction is highly dependent on crystal orientation/alignment, especially the availability of open ion channels. Interfaces bearing open ion paths of NCM are more susceptible to interdiffusion, but stabilize with the early formed passivation layer. Conversely, interfaces with closed ion pathway exhibit stability at intermediate temperatures, but deteriorate rapidly at high temperature due to oxygen evolution, increasing interfacial resistance. The elucidation of these distinct interfacial behaviors emphasizes the need for decoupling collective interfacial properties to enable rational design in solid-state batteries.

Temperature Sensitive Glutamate Gating of AMPA-subtype iGluRs.

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate the majority of excitatory neurotransmission1. iGluRs are gated by glutamate, where upon glutamate binding, they open their ion channels to enable cation influx into post-synaptic neurons, initiating signal transduction2. The structural mechanism of iGluR gating by glutamate has been extensively studied in the context of positive allosteric modulators (PAMs)3-15. A fundamental question has remained - are the PAM activated states of iGluRs representative of glutamate gating in the absence of PAMs? Here, using the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype iGluR (AMPAR) we show that glutamate gating is unique from gating in the presence of PAMs. We demonstrate that glutamate gating is temperature sensitive, and through temperature-resolved cryo-electron microscopy (cryo-EM), capture all major glutamate gating states. Physiological temperatures augment channel activation and conductance. Activation by glutamate initiates ion channel opening that involves all ion channel helices hinging away from the pores axis in a motif that is conserved across all iGluRs. Desensitization occurs when the local dimer pairs decouple and enables closure of the ion channel below through restoring the channel hinges and refolding the channel gate. Our findings define how glutamate gates iGluRs, provide foundations for therapeutic design, and point to iGluR gating being temperature sensitive.

3D morphology of an outer-hair-cell hair bundle increases its displacement and dynamic range

In mammals, outer-hair-cell hair bundles (OHBs) transduce sound-induced forces into receptor currents and are required for the wide dynamic range and high sensitivity of hearing. OHBs differ conspicuously in morphology from other types of bundles. Here, we show that the 3D morphology of an OHB greatly impacts its mechanics and transduction. An OHB comprises rod-like stereocilia, which pivot on the surface of its sensory outer hair cell. Stereocilium pivot positions are arranged in columns and form a V shape. We measure the pivot positions and determine that OHB columns are far from parallel. To calculate the consequences of an OHB’s V shape and far-from-parallel columns, we develop a mathematical model of an OHB that relates its pivot positions, 3D morphology, mechanics, and receptor current. We find that the 3D morphology of the OHB can halve its stiffness, can double its damping coefficient, and causes stereocilium displacements driven by stimulus forces to differ substantially across the OHB. Stereocilium displacements drive the opening and closing of ion channels through which the receptor current flows. Owing to the stereocilium-displacement differences, the currents passing through the ion channels can peak versus the stimulus frequency and vary considerably across the OHB. Consequently, the receptor current peaks versus the stimulus frequency. Ultimately, the OHB’s 3D morphology can increase its receptor-current dynamic range more than twofold. Our findings imply that potential pivot-position changes owing to development, mutations, or location within the mammalian auditory organ might greatly alter OHB function.

5β-Dihydrosteroids: Formation and Properties.

5β-Dihydrosteroids are produced by the reduction of Δ4-3-ketosteroids catalyzed by steroid 5β-reductase (AKR1D1). By analogy with steroid 5α-reductase, genetic deficiency exists in AKR1D1 which leads to errors in newborn metabolism and in this case to bile acid deficiency. Also, like the 5α-dihydrosteroids (e.g., 5α-dihydrotestosterone), the 5β-dihydrosteroids produced by AKR1D1 are not inactive but regulate ligand access to nuclear receptors, can act as ligands for nuclear and membrane-bound receptors, and regulate ion-channel opening. For example, 5β-reduction of cortisol and cortisone yields the corresponding 5β-dihydroglucocorticoids which are inactive on the glucocorticoid receptor (GR) and provides an additional mechanism of pre-receptor regulation of ligands for the GR in liver cells. By contrast, 5β-pregnanes can act as neuroactive steroids at the GABAA and NMDA receptors and at low-voltage-activated calcium channels, act as tocolytic agents, have analgesic activity and act as ligands for PXR, while bile acids act as ligands for FXR and thereby control cholesterol homeostasis. The 5β-androstanes also have potent vasodilatory properties and work through blockade of Ca2+ channels. Thus, a preference for 5β-dihydrosteroids to work at the membrane level exists via a variety of mechanisms. This article reviews the field and identifies gaps in knowledge to be addressed in future research.

Noise intensity of a Markov chain.

Stochastic transitions between discrete microscopic states play an important role in many physical and biological systems. Often these transitions lead to fluctuations on a macroscopic scale. A classic example from neuroscience is the stochastic opening and closing of ion channels and the resulting fluctuations in membrane current. When the microscopic transitions are fast, the macroscopic fluctuations are nearly uncorrelated and can be fully characterized by their mean and noise intensity. We show how, for an arbitrary Markov chain, the noise intensity can be determined from an algebraic equation, based on the transition rate matrix; these results are in agreement with earlier results from the theory of zero-frequency noise in quantum mechanical and classical systems. We demonstrate the validity of the theory using an analytically tractable two-state Markovian dichotomous noise, an eight-state model for a calcium channel subunit (De Young-Keizer model), and Markov models of the voltage-gated sodium and potassium channels as they appear in a stochastic version of the Hodgkin-Huxley model.

Spontaneous Transition between Multiple Conductance States and Rectifying Behaviors in an Artificial Single‐Molecule Funnel

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel‐shaped single‐molecule channel constructed by an electron‐deficient macrocycle and two electron‐deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non‐linear and rectifying I‐V relationship, indicating voltage‐dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism.

Understanding the Muscarinic Acetylcholine M3 Receptor: Structure, Function, and Therapeutic Implications

Muscarinic acetylcholine M receptors (mAChRs) belong to the G protein-coupled receptor (GPCR) superfamily and play a crucial role in regulating and controlling the release of acetylcholine (ACh). This review aims to focus on M3 receptor (M3R) subtype distribution, function, efficacy, and clinical applications. Specifically, we will delve into the M3R, encoded by the CHMR3 gene, which is primarily found in the cerebral cortex, airway, digestive tract, and glands. Under normal healthy conditions, M3Rs participate in various significant physiological reactions. They are involved in regulating the release of second messengers and controlling the opening of ion channels. Such functions contribute to maintaining essential processes within the body. In pathological conditions, M3Rs become potential therapeutic targets. Pharmacological manipulation using M3R agonists or antagonists can be utilized in treating a range of diseases, including schizophrenia, Alzheimer's disease (AD), type Ⅱ diabetes (T2D), congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), acute pancreatitis (AR), and overactive bladder (OAB). These receptors hold promise as proven or potential targets for effective disease management. Therefore, understanding the pharmacological properties and molecular mechanisms of M3R is vital for developing multi-target drugs (MTAs) to treat diseases with complex pathogenesis. This approach can help avoid the decline in drug efficacy caused by drug resistance. Exploiting the unique three-dimensional structure of M3Rs and their selective preference for different ligands, selective or non-selective pharmaceutical reagents for targeted therapy can be designed. Understanding these characteristics can facilitate the design of drugs that interact optimally with the receptor, potentially enhancing therapeutic outcomes.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

Ca2+ Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Regulation of calcium entry by cyclic GMP signaling in Toxoplasma gondii

Ca2+ signaling impacts almost every aspect of cellular life. Ca2+ signals are generated through the opening of ion channels that permit the flow of Ca2+ down an electrochemical gradient. Cytosolic Ca2+ fluctuations can be generated through Ca2+ entry from the extracellular milieu or release from intracellular stores. In Toxoplasma gondii, Ca2+ ions play critical roles in several essential functions for the parasite, like invasion of host cells, motility, and egress. Plasma membrane Ca2+ entry in T.gondii was previously shown to be activated by cytosolic calcium and inhibited by the voltage-operated Ca2+ channel blocker nifedipine. However, Ca2+ entry in T.gondii did not show the classical characteristics of store regulation. In this work, we characterized the mechanism by which cytosolic Ca2+ regulates plasma membrane Ca2+ entry in extracellular T.gondii tachyzoites loaded with the Ca2+ indicator Fura-2. We compared the inhibition by nifedipine with the effect of the broad spectrum TRP channel inhibitor, anthranilic acid or ACA, and we find that both inhibitors act on different Ca2+ entry activities. We demonstrate, using pharmacological and genetic tools, that an intracellular signaling pathway engaging cyclic GMP, protein kinase G, Ca2+, and the phosphatidyl inositol phospholipase C affects Ca2+ entry and we present a model for crosstalk between cyclic GMP and cytosolic Ca2+ for the activation of T.gondii's lytic cycle traits.

Promoting Articular Cartilage Regeneration through Microenvironmental Regulation.

In recent years, as the aging population continues to grow, osteoarthritis (OA) has emerged as a leading cause of disability, with its incidence rising annually. Current treatments of OA include exercise and medications in the early stages and total joint replacement in the late stages. These approaches only relieve pain and reduce inflammation; however, they have significant side effects and high costs. Therefore, there is an urgent need to identify effective treatment methods that can delay the pathological progression of this condition. The changes in the articular cartilage microenvironment, which are complex and diverse, can aggravate the pathological progression into a vicious cycle, inhibiting the repair and regeneration of articular cartilage. Understanding these intricate changes in the microenvironment is crucial for devising effective treatment modalities. By searching relevant research articles and clinical trials in PubMed according to the keywords of articular cartilage, microenvironment, OA, mechanical force, hypoxia, cytokine, and cell senescence. This study first summarizes the factors affecting articular cartilage regeneration, then proposes corresponding treatment strategies, and finally points out the future research direction. We find that regulating the opening of mechanosensitive ion channels, regulating the expression of HIF-1, delivering growth factors, and clearing senescent cells can promote the formation of articular cartilage regeneration microenvironment. This study provides a new idea for the treatment of OA in the future, which can promote the regeneration of articular cartilage through the regulation of the microenvironment so as to achieve the purpose of treating OA.

Efficient Detection of Ion Channel Switching through Rapid Random Forest Models

The proper function of ion channels is fundamental to many of our physiological processes, such as neural signal transmission, muscle contraction, and insulin secretion. As a result of genetic mutations and environmental factors, however, the dysfunction of ion channels can impede crucial cellular processes, resulting in channelopathies, such as cystic fibrosis and hypoglycemia, which may lead to highly impaired respiratory, cardiovascular, and muscular function. To detect ion channel dysfunction, a GPU-accelerated random forest model with an F1-score of 0.935 was developed to efficiently analyze electrophysiological time series data for the improper opening and closing of ion channels. The random forest model can run 200x faster than real-time 10 kHz electrophysiological data collection, holding immense potential for the development of reactive clinical measures for ion channel dysfunction and the development of novel therapies for various ion channel-based musculoskeletal disorders.

Rational Design of High-Performance Electrodes Based on Ferric Oxide Nanosheets Deposited on Reduced Graphene Oxide for Advanced Hybrid Supercapacitors.

The core strategy for constructing ultra-high-performance hybrid supercapacitors is the design of reasonable and effective electrode materials. Herein, a facile solvothermal-calcination strategy is developed to deposit the phosphate-functionalized Fe2O3 (P-Fe2O3) nanosheets on the reduced graphene oxide (rGO) framework. Benefiting from the superior conductivity of rGO and the high conductivity and fast charge storage dynamics of phosphate ions, the synthesized P-Fe2O3/rGO anode exhibits remarkable electrochemical performance with a high capacitance of 586.6Fg-1 at 1Ag-1 and only 4.0% capacitance loss within 10000 cycles. In addition, the FeMoO4/Fe2O3/rGO nanosheets are fabricated by utilizing Fe2O3/rGO as the precursor. The introduction of molybdates successfully constructs open ion channels between rGO layers and provides abundant active sites, enabling the excellent electrochemical features of FeMoO4/Fe2O3/rGO cathode with a splendid capacity of 475.4C g-1 at 1Ag-1. By matching P-Fe2O3/rGO with FeMoO4/Fe2O3/rGO, the constructed hybrid supercapacitor presents an admirable energy density of 82.0Whkg-1 and an extremely long working life of 95.0% after 20000 cycles. Furthermore, the continuous operation of the red light-emitting diode for up to 30min demonstrates the excellent energy storage properties of FeMoO4/Fe2O3/rGO//P-Fe2O3/rGO, which provides multiple possibilities for the follow-up energy storage applications of the iron-based composites.

Accelerating ion and charge transfer of hybrid titanium niobium oxides through interface engineering for high-performance lithium ion capacitors

Titanium niobium oxides have garnered significant attention as potential anode materials for lithium ion capacitors (LICs) due to their open ionic channels and high safety. However, the sluggish ion and charge transfer kinetics impede their rate capability. Hereby, we have investigated the phases evolution process of titanium niobium oxides by simple optimizing Nb/Ti ratio in the precursor, leading to the successful construction of hybrid TiO2/TiNb2O7 with active interface. Density functional theory (DFT) calculations manifest the low Li+-diffusion barrier and the formation of built-in electric fields, resulting in the accelerated interfacial charge separation/transfer and Li+ diffusion. In-situ XRD results reveal the highly reversible structural changes of TiO2/TiNb2O7 during charging/discharging process. Accordingly, hybrid TiO2/TiNb2O7 demonstrates much reinforced rate capability, which could retain a specific capacity of 205.1 mAh g−1 at high current density of 10 A g−1 compared to 300.3 mAh g−1 at 0.1 A g−1. Moreover, the assembled TiO2/TiNb2O7//AC LIC displays high energy density of 149.6 W h kg−1 (at 200 W kg−1). Overall, this work emphasizes the critical role of interface engineering in promoting ion and charge transfer of nanomaterials for superior energy storage and beyond.

Hair Growth Promotion and Anti-Hair Loss Effects of By-Products Arabica Coffee Pulp Extracts Using Supercritical Fluid Extraction.

Coffee has been a common ingredient in many traditional hair loss remedies, but limited scientific evidence supports its use, particularly in coffee pulp. Androgenetic alopecia (AGA) is caused by androgens, inflammation, and oxidative stress. In the present study, supercritical fluid extraction (SFE) was used under various conditions to obtain six coffee pulp extracts. The SFE-4 extract, using 50% (v/v) ethanol as a co-solvent at conditions of 100 °C and 500 bars for 30 min, exhibited the highest phenolic, flavonoid, and caffeine contents. Additionally, the SFE-4 extract increased the migration and cell proliferation of HFDPCs (human hair follicle dermal papilla cells), which control hair cycle regulation, and had scavenging effects on ABTS and DPPH radicals. Additionally, the SFE-4 extract showed potassium ion channel opener activity in HFDPCs, as well as a stimulation effect on the enzyme matrix metalloproteinase-2 (MMP-2) (28.53 ± 1.08% of control), which may be related to the vascular endothelial growth factor (VEGF) gene upregulation. In human prostate cancer cells (DU-145) and HFDPC cells, the SFE-4 extract significantly decreased the expression of SRD5A1, SRD5A2, and SRD5A3, an essential pathway involved in AGA. Hair growth factor genes in the Wnt/-catenin (CTNNB1) and Sonic Hedgehog (SHH, SMO, and GLI1) pathways could be significantly activated by the SFE-4 extract. These results imply that employing SFE in coffee pulp extraction could help AGA treatment by preventing hair loss and promoting hair growth pathways. This would help small coffee producers gain economic empowerment and ensure the long-term sustainability of agricultural waste utilization.

Controversial Issues of the Mechanism of Crystalline Lens Accommodation and the Rationale the Hydraulic Component in its Implementation

Purpose: To consider controversial issues of the mechanism of crystalline lens accommodation and to justify the hydraulic component in its implementation.
 Materials and Methods: Theories of the mechanism of accommodation and its assessment according to ultrasound biomicroscopy, magnetic resonance imaging and optical coherence tomography were analyzed. For the first time, the features of accommodative activation of intraocular fluid exchange in the closed hydrostatic system of the lens with the participation of mechanosensitive aquaporins were considered. When substantiating the hydraulic component in the mechanism of the crystalline lens accommodation, special emphasis was placed on the rapid decrease in pressure in the anterior and posterior chambers of the eye during contraction of the meridional portion of the ciliary muscle.
 Results: Analysis of various theories of accommodation has shown that mechanism of the crystalline lens its implementation continues to be discussed to this day. For the first time, the lens was considered as a unique closed hydrostatic system in which the pressure level is established through ultrafiltration and diffusion of intraocular fluid with the participation of aquaporins. Aquaporins form ion channels in the capsule, cuboidal epithelial cells, lens fibers and are mechanosensitive receptor proteins. The opening and closing of ion channels regulates the potassium-sodium pump, directed transport and exchange of intraocular fluid in the lens. The hydrostatic balance between the pressure in the crystalline lens and the anterior and posterior chambers of the eye is ensured by the crystalline lens capsule. The capsular bag of the crystalline lens can be considered as a curved diaphragm that separates two hydrostatic systems with different levels of pressure. Due to the hydrostatic buffering effect, the IOP level does not affect the crystalline lens, but it responds to a rapid decrease. This decrease in pressure in the anterior and posterior chambers is realized through the tension of the scleral spur by the meridional portion of the ciliary muscle and the activation of the valve mechanism of the scleral sinus. The greater the decrease in pressure, the more convex the crystalline lens takes on and increases its refraction.
 Conclusion: The presence of a hydraulic component in the mechanism of crystalline lens accommodation allows us to understand how the contraction of the small ciliary muscle can change the shape and refractive power of the large crystalline lens.

Fluid shear stress enhances dendritic cell activation

Ex vivo activation of dendritic cells (DCs) has been widely explored for targeted therapies, although these treatments remain expensive. Reducing treatment costs while enhancing cell activation could help to make immunotherapies more accessible. Cells can be activated by both internal and external forces including fluid shear stress (FSS). FSS activates cells via opening of mechanosensitive ion channels. In this study, dendritic cells were activated by sustained exposure to circulatory levels of fluid shear stress using a cone-and-plate flow device and analyzed for activation markers. After 1 h of shear stress exposure, an increase in cytokine release was present in immortalized cells as well as phosphorylation of the proteins NF-κB and cFos in primary DCs. Changes in DC morphology, metabolism and proliferation were also observed. These compelling new findings point to the potential for using FSS to activate DCs for ex vivo therapeutics.