Cation Fluxes Research Articles

Small molecules targeting the NADH-binding pocket of VDAC modulate mitochondrial metabolism in hepatocarcinoma cells.

Voltage dependent anion channels (VDAC) control the flux of most anionic respiratory substrates, ATP, ADP, and small cations, crossing the outer mitochondrial membrane. VDAC closure contributes to the partial suppression of mitochondrial metabolism that favors the Warburg phenotype of cancer cells. Recently, it has been shown that NADH binds to a specific pocket in the inner surface of VDAC1, also conserved in VDAC2 and 3, closing the channel. We hypothesized that binding of small molecules to the NADH pocket, maintain VDAC in an open configuration by preventing closure induced by NADH and possible other endogenous regulators. We screened in silico, the South Carolina Compound Collection SC3 (~ 100,000 proprietary molecules), using shape-based queries of the NADH binding region of VDAC. After molecular docking of selected compounds, we physically screened candidates using mitochondrial membrane potential (ΔΨm), as an overall readout of mitochondrial metabolism. We identified SC18, as the most potent compound. SC18 bound to VDAC1, as assessed by a thermal shift assay. Short-term treatment with SC18 decreased ΔΨm in SNU-449 and HepG2 human hepatocarcinoma cells. Mitochondrial depolarization was similar in wild type, VDAC1/2, 1/3, and 2/3 double KO HepG2 cells indicating that the effect of SC18 was not VDAC isoform-dependent. In addition, SC18 decreased mitochondrial NADH and cellular ATP production; and increased basal respiration. Long-term exposure to SC18, decreased cell proliferation as determined by wound-healing and cell viability assays. In summary, SC18 is a novel VDAC-targeting small molecule that induces mitochondrial dysfunction and inhibits cell proliferation.

The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytes.

The mechanoelectrical feedback (MEF) mechanism in the heart that plays a significant role in the occurrence of arrhythmias, involves cation flux through cation nonselective stretch‐activated channels (SACs). It is well known that nitric oxide (NO) can act as a regulator of MEF. Here we addressed the possibility of SAC’s regulation along NO‐dependent and NO‐independent pathways, as well as the possibility of S‐nitrosylation of SACs. In freshly isolated rat ventricular cardiomyocytes, using the patch‐clamp method in whole‐cell configuration, inward nonselective stretch‐activated cation current ISAC was recorded through SACs, which occurs during dosed cell stretching. NO donor SNAP, α1‐subunit of sGC activator BAY41‐2272, sGC blocker ODQ, PKG blocker KT5823, PKG activator 8Br‐cGMP, and S‐nitrosylation blocker ascorbic acid, were employed. We concluded that the physiological concentration of NO in the cell is a necessary condition for the functioning of SACs. An increase in NO due to SNAP in an unstretched cell causes the appearance of a Gd3+‐sensitive nonselective cation current, an analog of ISAC , while in a stretched cell it eliminates ISAC . The NO‐independent pathway of sGC activation of α subunit, triggered by BAY41‐2272, is also important for the regulation of SACs. Since S‐nitrosylation inhibitor completely abolishes ISAC , this mechanism occurs. The application of BAY41‐2272 cannot induce ISAC in a nonstretched cell; however, the addition of SNAP on its background activates SACs, rather due to S‐nitrosylation.ODQ eliminates ISAC , but SNAP added on the background of stretch increases ISAC in addition to ODQ. This may be a result of the lack of NO as a result of inhibition of NOS by metabolically modified ODQ. KT5823 reduces PKG activity and reduces SACs phosphorylation, leading to an increase in ISAC . 8Br‐cGMP reduces ISAC by activating PKG and its phosphorylation. These results demonstrate a significant contribution of S‐nitrosylation to the regulation of SACs.

Canonical approach to cation flux calibration in oxide molecular-beam epitaxy

Molecular-beam epitaxy (MBE) is the gold standard for the epitaxial growth of complex oxides with the best material properties as determined by respective figures of merit. Unfortunately, once more than one cation is involved in the material desired, MBE growth often becomes plagued by difficulties in stoichiometry control. Instead of relying on a quartz crystal microbalance to measure the fluxes of the individual molecular beams, which lacks accuracy, or reflection high-energy electron diffraction oscillations of the targeted multication oxide in layer-by-layer growth, which lacks general applicability, here, we describe a canonical approach based on the growth of films of the constituent binary oxides or metals individually for cation flux calibration. This method can calibrate the flux of each molecular beam with an absolute accuracy of \ifmmode\pm\else\textpm\fi{}1%. After describing the growth parameters of binary oxides or metals enabling the individual fluxes of 39 elements of the periodic table to be determined, we demonstrate the efficacy of this approach by applying it to the growth of the quaternary ferromagnetic metal ${\mathrm{La}}_{0.5}{\mathrm{Sr}}_{0.5}\mathrm{Co}{\mathrm{O}}_{3\ensuremath{-}\ensuremath{\delta}}$ to achieve films with transport properties rivalling the best reported using thin-film growth techniques providing stoichiometric transfer.

Microscopic Insights into Cation-Coupled Electron Hopping Transport in a Metal-Organic Framework.

Electron transport through metal–organic frameworks by a hopping mechanism between discrete redox active sites is coupled to diffusion-migration of charge-balancing counter cations. Experimentally determined apparent diffusion coefficients, Deapp, that characterize this form of charge transport thus contain contributions from both processes. While this is well established for MOFs, microscopic descriptions of this process are largely lacking. Herein, we systematically lay out different scenarios for cation-coupled electron transfer processes that are at the heart of charge diffusion through MOFs. Through systematic variations of solvents and electrolyte cations, it is shown that the Deapp for charge migration through a PIZOF-type MOF, Zr(dcphOH-NDI) that is composed of redox-active naphthalenediimide (NDI) linkers, spans over 2 orders of magnitude. More importantly, however, the microscopic mechanisms for cation-coupled electron propagation are contingent on differing factors depending on the size of the cation and its propensity to engage in ion pairs with reduced linkers, either non-specifically or in defined structural arrangements. Based on computations and in agreement with experimental results, we show that ion pairing generally has an adverse effect on cation transport, thereby slowing down charge transport. In Zr(dcphOH-NDI), however, specific cation–linker interactions can open pathways for concerted cation-coupled electron transfer processes that can outcompete limitations from reduced cation flux.

Promoting Electroosmotic Water Flow through a Carbon Nanotube by Weakening the Competition between Cations and Anions in a Lateral Electric Field.

Understanding the electroosmotic flow through a nanochannel is essential to the design of novel nanofluidic devices, ranging from desalination to nanometer water pumps. Nonetheless, the competition between cation and anion in electric fields inevitably leads to a limited pumping of water, and thus weakening their competition could be a new avenue for the fundamental control of water transport. In this work, through a series of molecular dynamics simulations, we find a surprising phenomenon in which under the drive of a traditional longitudinal electric field, an additional lateral electric field can significantly weaken the competitive transport of a cation and anion through a carbon nanotube, which spontaneously leads to a massive increase in electroosmotic water flux. Specifically, with the increase in the lateral electric field, the anion flux exhibits an almost linear reduction, and the cation flux is stable and can even be enhanced. As a result, the net water flux along the cation direction increases significantly. The key to this unexpected phenomenon lies in the size and mobility difference between the cation and anion. The anion is larger and has greater mobility and is thus more susceptible to the lateral electric field, which ultimately leads to the reduction of its flux. For different ion types and CNT lengths, we can observe similar electropumping phenomenon, where the friction force induced by the lateral electric field becomes nontrivial for long CNTs. Our results provide a new route to tune the competitive transport of cations and anions and should be useful for the design of novel electroosmotic pumps.

Tracking Passivation and Cation Flux at Incipient Solid‐Electrolyte Interphases on Multi‐Layer Graphene using High Resolution Scanning Electrochemical Microscopy

AbstractThe solid electrolyte interphase (SEI) is a dynamic, electronically insulating film that forms on the negative electrode of Li+ batteries (LIBs) and enables ion movement to/from the interface while preventing electrolyte breakdown. However, there is limited comparative understanding of LIB SEIs with respect to those formed on Na+ and K+ electrolytes for emerging battery concepts. We used scanning electrochemical microscopy (SECM) for the in situ interfacial analysis of incipient SEIs in Li+, K+ and Na+ electrolytes formed on multi‐layer graphene. Feedback images using 300 nm SECM probes and ion‐sensitive measurements indicated a superior passivation and highest cation flux for a Li+‐SEI in contrast to Na+ and K+‐SEIs. Ex situ X‐ray photoelectron spectroscopy indicated significant fluoride formation for only Li+ and Na+‐SEIs, enabling correlation to in situ SECM measurements. While SEI chemistry remains complex, these electroanalytical methods reveal links between chemical variables and the interfacial properties of materials for energy storage.

Effects of Forest Type on Nutrient Fluxes in Throughfall, Stemflow, and Litter Leachate within Acid-Polluted Locations in Southwest China.

Although new inputs of acidic anions are decreasing, soil acidification still deserves more academic attention because of the effects of historical stores of SO42− already absorbed into soils. Forest canopy has large, species-specific effects on rainwater chemistry, for which the hydrological mechanism remains unclear. We investigated precipitation, throughfall, stemflow, and litter leachate across three forest types in a severely acid-polluted site located in Southwest China. Precipitation monitored over 4 months, representing summer, fall, winter, and spring, indicated neutral precipitation in Tieshanping with pH ranging from 6.58–7.33. Throughfall and litter leachate in Pinus massoniana Lamb. stands were enriched with greater cation and anion fluxes, as well as more dissolved organic carbon (DOC) flux. Rainwater from pure stands of Cinnamomum camphora (Linn) Presl yielded lower N and DOC inputs to soils with higher base saturation, which would reduce soil acidification and, therefore, improve the sustainability of forest ecosystems.

Source to sink analysis of weathering fluxes in Lake Baikal and its watershed based on riverine fluxes, elemental lake budgets, REE patterns, and radiogenic (Nd, Sr) and 10Be/9Be isotopes

We present a detailed analysis of weathering fluxes at Lake Baikal, the largest lake in the world, using the major element, trace element and isotope geochemistry of major inflowing rivers, the lake itself, and its sediments. Our objective is to assess how lake records could be used to understand river-catchment-scale denudation and weathering processes.Total denudation rates at Lake Baikal, as obtained from meteoric 10Be/9Be, are an order of magnitude lower than the global average, at 16–35 t km−2 yr−1. Chemical weathering rates obtained from the riverine dissolved load and discharge are, on the other hand, in the same range as global values, at 6–29 t km−2 yr−1. Chemical weathering rates are higher in the north of the catchment than in the south, consistent with higher runoff in the north. In contrast, 10Be/9Be-derived denudation rates are higher in the south. We hypothesize that this pattern of variation may be due to the stabilizing effect of permafrost soils preventing erosion in the north. An inverse model shows that the Selenga River, Lake Baikal’s major tributary, has a silicate weathering contribution to riverine dissolved cation fluxes of 42 mol%; this and other characteristics are representative of large rivers globally. Many trace elements have much lower concentrations in the lake than in inflowing rivers (Be (5%), Mn (3%), Fe (0.4%) and REE (1–2%)). We suggest, based on REE patterns and Mn, Fe-depth profiles in the lake, that this removal is the result of pH induced changes in dissolved-adsorbed partitioning at the river-lake interface, and the incorporation of trace elements into authigenic Fe-Mn (oxyhydr)oxide phases forming within the lake. Strontium is isotopically uniform within the lake, demonstrating that the whole lake mixes on a timescale shorter than its residence time (<330 years). Neodymium and Be, in contrast, show isotopic variability between the basins. While the Sr isotope budget of the lake is largely consistent with observed riverine Sr fluxes, an unradiogenic Nd source is needed to explain lake Nd isotope compositions, especially in the Northern Basin. This source appears to derive from old crustal rocks in this part of the catchment and could be hydrothermal, or small rivers that were not sampled here. Similarly, elevated 10Be/9Be ratios in the lake basins relative to the river input imply variable but significant atmospheric inputs of 10Be into the lake.Overall, this study demonstrates that records of the paleo-chemistry of lakes, and Lake Baikal in particular, hold promise for understanding denudation and weathering on the continents, in ways that are more directly relatable to the environmental conditions of the catchment than is possible with marine records.

Mussel-inspired tannic acid/polyethyleneimine assembling positively-charged membranes with excellent cation permselectivity

The extraction of valuable target ions through monovalent cation exchange membranes (MCEMs) has been increasingly attracting in modern energy and environmental fields. However, the separation performance of MCEMs in terms of the permselectivity and cation fluxes, is typically restricted by membrane architecture and applied materials. Recently, mussel-inspired surface modification methods have been deployed in new membrane fabrications with special surface characteristics and functions. Herein, a facile layer-by-layer assembly method was designed to construct a series of de novo positively-charged tannic acid/polyethyleneimine (TA/PEI) membranes containing a negatively-charged support membrane and a TA/PEI selective layer. Notably, the peculiar support membrane with a much dense structure and abundant cation exchange groups can enable our TA/PEI membranes to possess high total cation fluxes. The selective layer with vast positive charges ensures mussel-inspired TA/PEI assembled positively-charged membranes to have a high permselectivity. Most importantly, compared with the separation performance of the state-of-the-art MCEMs, the superior separation performance of our developed new MCEMs at 5 mA·cm−2 and 10 mA·cm−2 is beyond the current “Upper Bound” plot between Na+ flux and the permselectivity (Na+/Mg2+), which opens new avenues for the construction of MCEMs. Furthermore, high purity of Li+ (95.37%) can be obtained through deploying mussel-inspired TA/PEI assembled positively-charged membranes with high permselectivity of Li+/Mg2+ (13.72), proving its great potentials in the field of resource recovery towards sustainability.

Gap edge canopy buffering of throughfall deposition in a subalpine natural forest

Base cation loads are rarely considered in forest gap edge canopies, but they can play critical roles in capturing or buffering atmospheric deposition in forests with frequent gap disturbances, such as subalpine forests. We selected an expanded gap edge canopy and a closed canopy in a subalpine natural forest on the eastern Tibetan Plateau. The throughfall deposition and canopy exchange processes of common base cations (K + , Ca 2+ , Na + , and Mg 2+ ) were continuously studied over two years. The results showed that the enrichment ratio and fluxes had lower levels of base cations in the gap-edge canopy than in the closed canopy, which indicated that base cations were concentrated more in the closed canopy than in the gap-edge canopy. Although Ca 2+ in the gap-edge canopy showed a higher net throughfall flux, the annual net throughfall fluxes of K + , Na + and Mg 2+ within the gap-edge canopy were 1.83, 6.75 and 2.95 times lower than those in the closed canopy, respectively. Moreover, dry deposition fluxes of base cations significantly decreased in the gap edge canopy compared to those in the closed canopy, and the decreasing tendency was more significant during the snowy season than during the rainy season. Overall, these results suggest that the amount of base cations in subalpine natural forest ecosystems may be overestimated when the throughfall deposition of ions in gap edge canopies is ignored.

An electrodeposition model with surface relaxation predicts temperature and current effects in compact and dendritic film morphologies.

We study a thin-film electrodeposition model that represents the relaxation of the deposited material by adatom diffusion on quenched crystal topographies and considers simple mechanisms of cation flux in the electrolyte. The results of numerical simulations with collimated flux and a rapid cation reduction in contact with the deposit relate the surface roughness and the adatom hop numbers with two model parameters. A comparison with the results of a collective diffusion model for vapor deposition shows differences in the surface morphologies but similarities in scaling relations, which suggest thermally activated (Arrhenius) forms for the parameters of the electrodeposition model and relate one of them to the applied current. Simulations with purely diffusive cation flux and possible pore formation in simple cubic lattices show the growth of self-organized structures with leaf shapes (dendrites) above a compact layer that covers the flat electrode. The thickness of this layer and the average dendrite size also obey scaling relations in terms of the model parameters, which predict that both sizes decrease with the applied current, in agreement with recent experimental studies. Under all flux conditions, an increase in adatom diffusivity with temperature implies an increase in the average sizes of low-energy surface configurations, independently of their particular shapes. Finally, we note that a previously proposed model for electrodeposition produced similar morphologies, but the quantitative relations for the characteristic sizes differ from those of the present model, which also advances with a consistent interpretation of temperature effects.

Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases.

Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1β (pro-IL-1β)-degrading caspase-1 to lead to IL-1β release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.

Double‐Network Ion Channels for High‐Performance Osmotic Power Generation

AbstractBiomimetic nanochannels are desirable materials for high‐efficiency utilization of osmotic energy. However, the current power generation performance is limited by the low ion selectivity and ion flux. Here, novel nanochannels with double‐network structure based on cellulose nanofibers intercalated with carbon nanotubes are demonstrated. The relatively high cationic selectivity and ion flux are obtained due to the enlarged charge polarity and space for ion transport in the double‐network nanochannel, which is favorable for the osmotic power conversion. To the best of the authors’ knowledge, the power density under 50‐fold NaCl (4.67 W m−2) outperforms most state‐of‐the‐art nanochannel membranes with the same test conditions. By applying the concentration gradient between artificial (50‐fold KCl) and real seawater/river water, a high power density of 5.53 and 6.51 W m−2 can be achieved respectively, which exceeds the standard output of the ion‐selective membrane for commercialization. The design of the biomimetic double‐network nanochannels provides a new platform for controllable ion transport and high‐performance power generation.

Distribution of ion pairs into a bilayer lipid membrane and its effect on the ionic permeability.

This work reports the distribution constant of a target ion and a counter-ion between an aqueous phase and an artificial bilayer lipid membrane (BLM) and its influence to the ionic permeability through a BLM. A theoretical formula for ionic permeability through a BLM based on the distribution of the target ion and the counter-ion is also proposed and validated by analyzing the flux of a fluorescent cation [rhodamine 6G (R6G+)] through the BLM in the presence of counter-ions (X- =Br-, BF4-, and ClO4-). The transmembrane flux was evaluated by simultaneous measurement of the transmembrane current density and the transmembrane fluorescence intensity as a function of the membrane potential. The distribution constant of R6G+ and X- between the aqueous and BLM phases was determined by a liposome-extraction method. The measured ionic permeability exhibited non-linear dependent on the aqueous concentration of R6G+ or X-, but proportional to the concentration of R6G+ and X- inside the BLM evaluated from the distribution constant of R6G+ and X-. The proportionality demonstrates that the distribution of cations and anions between the aqueous and BLM phases dominates the flux of ion transport through the BLM. The proposed formula can express the dependence of the transmembrane current on the membrane potential and the concentrations of R6G+ and X- in the aqueous phase.

Comprehensive characterization of Guanosine monophosphate synthetase in Nicotiana tabacum.

Guanosine monophosphate (GMP) synthetase is an enzyme that converts xanthosine monophosphate to GMP. GMP plays an essential role in plant development and responses to internal and external stimuli. It also plays a crucial role in several plant physiochemical processes, such as stomata closure, cation flux regulation, pathogen responses and chloroplast development. The mRNA sequences of NtGMP synthase in tobacco (Nicotiana tabacum) were rapidly amplified from cDNA. The GMP synthase open reading frame contains a 1617 bp sequence encoding 538 amino acids. A sequence analysis showed that this sequence shares high homology with that of Nicotiana sylvestris, Nicotiana attenuata, N. tomentosiformis, Solanum tuberosum, Lycopersicon pennellii, L. esculentum, Capsicum annuum, C. chinense and C. baccatum GMP synthase. A BLAST analysis with a tobacco high-throughput genomic sequence database revealed that the tobacco GMP synthase gene has five introns and six exons. A phylogenetic analysis showed a close genetic evolutionary relationship with N. sylvestris GMP synthase. The tissue-specific expression profile was evaluated using quantitative real-time PCR. The data showed that NtGMP synthase was highly expressed in leaves and moderately expressed in roots, flowers, and stems. The subcellular localization was predicted using the WOLF PSORT webserver, which strongly suggested that it might be localized to the cytoplasm. In the current study, we cloned and comprehensively characterized GMP synthase in tobacco (Nicotiana tabacum). Our results establish a basis for further research to explore the precise role of this enzyme in tobacco.

Electropumping Phenomenon in Modified Carbon Nanotubes.

Controlling the water transport in a given direction is essential to the design of novel nanofluidic devices, which is still a challenge because of thermal fluctuations on the nanoscale. In this work, we find an interesting electropumping phenomenon for charge-modified carbon nanotubes (CNTs) through a series of molecular dynamics simulations. In electric fields, the flowing counterions on the CNT inner surface provide a direct driving force for water conduction. Specifically, the dynamics of cations and anions exhibit distinct behaviors that lead to thoroughly different water dynamics in positively and negatively charged CNTs. Because of the competition between the increased ion number and ion-CNT interaction, the cation flux displays an interesting maximum behavior with the increase in surface charge density; however, the anion flux rises further at higher charge density because it is less attractive to the surface. Thus, the anion flux is always several times larger than cation flux that induces a higher water flux in positive CNTs with nearly 100% pumping efficiency, which highly exceeds the efficiency of pristine CNTs. With the change in charge density, the translocation time, occupancy number, and radial density profiles for water and ions also demonstrate a nontrivial difference for positive and negative CNTs. Furthermore, the ion flux exhibits an excellent linear relationship with the field strength, leading to the same water flux behavior. For the change in salt concentration, the pumping efficiency for positive CNTs is also nearly 100%. Our results provide significant new insight into the ionic transport through modified CNTs and should be helpful for the design of nanometer water pumps.

VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges.

Most anionic metabolites including respiratory substrates, glycolytic adenosine triphosphate (ATP), and small cations that enter mitochondria, and mitochondrial ATP moving to the cytosol, cross the outer mitochondrial membrane (OMM) through voltage dependent anion channels (VDAC). The closed states of VDAC block the passage of anionic metabolites, and increase the flux of small cations, including calcium. Consequently, physiological or pharmacological regulation of VDAC opening, by conditioning the magnitude of both anion and cation fluxes, is a major contributor to mitochondrial metabolism. Tumor cells display a pro-proliferative Warburg phenotype characterized by enhanced aerobic glycolysis in the presence of partial suppression of mitochondrial metabolism. The heterogeneous and flexible metabolic traits of most human tumors render cells able to adapt to the constantly changing energetic and biosynthetic demands by switching between predominantly glycolytic or oxidative phenotypes. Here, we describe the biological consequences of changes in the conformational state of VDAC for cancer metabolism, the mechanisms by which VDAC-openers promote cancer cell death, and the advantages of VDAC opening as a valuable pharmacological target. Particular emphasis is given to the endogenous regulation of VDAC by free tubulin and the effects of VDAC-tubulin antagonists in cancer cells. Because of its function and location, VDAC operates as a switch to turn-off mitochondrial metabolism (closed state) and increase aerobic glycolysis (pro-Warburg), or to turn-on mitochondrial metabolism (open state) and decrease glycolysis (anti-Warburg). A better understanding of the role of VDAC regulation in tumor progression is relevant both for cancer biology and for developing novel cancer chemotherapies.

Optimizing functional layer of cation exchange membrane by three-dimensional cross-linking quaternization for enhancing monovalent selectivity

Monovalent cation perm-selective membrane (MCPMs) allow fast and selective transport of monovalent cations, and they are promisingly required for extraction of special ions, such as lithium extraction, acid recovery and sea salt production. Herein, we report a novel strategy to design the critical functional layers of MCPMs with both space charge repulsion and cross-linked dense screenability. The in-situ deposition polymerization of pyrrole was carried out on the surface of sulfonated polyphenyl sulfone (SPPSU) substrate membrane followed by cross-linking quaternization of the polypyrrole (PPy) layer with diiodinated functional molecules, thus, the membrane obtained more excellent selective permeability and stable transport properties of monovalent cations. It confirms that the designed PPy layers with charged surface and cross-linking structure improved the hydrophilicity, facilitated cation transport and increased ion flux. Meanwhile, for the dense PPy layer, the charged cross-linked structure endowed the functional layer with the synergistic characteristics of Donnan exclusion and pore size sieving for positively charged ions, which improved the monovalent cation perm-selectivity of the membranes. At a constant current density of 5.1 mA/cm2, the optimal membrane exhibited superior perm-selectivity (PMgNa=2.07) and monovalent cation flux (JNa+ = 2.80 × 10 −8 mol cm−2 s−1) during electrodialysis.

TRPM7 is a crucial regulator of pancreatic endocrine development and high-fat-diet-induced β-cell proliferation.

The melastatin subfamily of the transient receptor potential channels (TRPM) are regulators of pancreatic β-cell function. TRPM7 is the most abundant islet TRPM channel; however, the role of TRPM7 in β-cell function has not been determined. Here, we used various spatiotemporal transgenic mouse models to investigate how TRPM7 knockout influences pancreatic endocrine development, proliferation and function. Ablation of TRPM7 within pancreatic progenitors reduced pancreatic size, and α-cell and β-cell mass. This resulted in modestly impaired glucose tolerance. However, TRPM7 ablation following endocrine specification or in adult mice did not impact endocrine expansion or glucose tolerance. As TRPM7 regulates cell proliferation, we assessed how TRPM7 influences β-cell hyperplasia under insulin-resistant conditions. β-Cell proliferation induced by high-fat diet was significantly decreased in TRPM7-deficient β-cells. The endocrine roles of TRPM7 may be influenced by cation flux through the channel, and indeed we found that TRPM7 ablation altered β-cell Mg2+ and reduced the magnitude of elevation in β-cell Mg2+ during proliferation. Together, these findings revealed that TRPM7 controls pancreatic development and β-cell proliferation, which is likely due to regulation of Mg2+ homeostasis.

Lorentz Force-Driven Autonomous Janus Swimmers.

Autonomous swimmers have been intensively studied in recent years due to their numerous potential applications in many areas ranging from biomedicine to environmental remediation. Their motion is based either on different self-propulsion mechanisms or on the use of various external stimuli. Herein, the synergy between the ion flux around self-electrophoretic Mg/Pt Janus swimmers and an external magnetic field is proposed as an efficient alternative mechanism to power swimmers on the basis of the resulting Lorentz force. A strong magnetohydrodynamic effect is observed due to the orthogonal combination of magnetic field and spontaneous ionic currents, leading to an increase of the swimmer speed by up to 2 orders of magnitude. Furthermore, the trajectory of the self-propelled swimmers can be controlled by the orientation of the magnetic field, due to the presence of an additional torque force caused by a horizontal cation flux along the swimmer edges, resulting in predictable clockwise or anticlockwise motion. In addition, this effect is independent of the swimmer size, since a similar type of rotational motion is observed for macro- and microscale objects.