Active Ion Transport Research Articles

Photocontrolled activation of doubly o-nitrobenzyl-protected small molecule benzimidazoles leads to cancer cell death.

Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal, healthy cells are very rare. Particularly, light-responsive systems promise better applicability for photodynamic therapy because of their spatiotemporal controllability, low toxicity, and high tunability. Here, in this work, we report o-nitrobenzyl-linked, benzimidazole-based singly and doubly protected photocaged protransporters 2a, 2b, 3a, and 3b, respectively, and benzimidazole-2-amine-based active transporters 1a-1d. Among the active compounds, trifluoromethyl-based anionophore 1a showed efficient ion transport activity (EC50 = 1.2 ± 0.2 μM). Detailed mechanistic studies revealed Cl-/NO3- antiport as the main ion transport process. Interestingly, double protection with photocages was found to be necessary to achieve the complete "OFF-state" that could be activated by external light. The procarriers were eventually activated inside the MCF-7 cancer cells to induce phototoxic cell death.

Functional assay of light-induced ion-transport by rhodopsins.

Microbial rhodopsins are photoreceptive membrane proteins found from diverse microorganisms such as archaea, eubacteria, eukaryotes and viruses. Many microbial rhodopsins possess ion-transport activity by light, such as channels and pumps, and ion-transporting rhodopsins are important tools in optogenetics that control animal behavior by light. Historically, molecular mechanism of rhodopsins has been studied by spectroscopic methods for purified proteins. On the other hand, ion-transport function has to be studied by different methods. This chapter introduces two methods of functional assay of ion-transporting rhodopsins by light. One is a patch clamp method using mammalian cells, and another is an ion-transport assay using pH electrode and microbial cells. These functional assay provides fundamental data of ion-transporting rhodopsins, and thus contributes to evaluation for optogenetic tools.

Two Trk/Ktr/HKT-type potassium transporters, TrkG and TrkH, perform distinct functions in Escherichia coli K-12

Escherichia coli K-12 possesses two versions of Trk/Ktr/HKT-type potassium ion (K+) transporters, TrkG and TrkH. The current paradigm is that TrkG and TrkH have largely identical characteristics, and little information is available regarding their functional differences. Here, we show using cation uptake experiments with K+ transporter knockout mutants that TrkG and TrkH have distinct ion transport activities and physiological roles. K+-transport by TrkG required Na+, whereas TrkH-mediated K+ uptake was not affected by Na+. An aspartic acid located five residues away from a critical glycine in the third pore-forming region might be involved in regulation of Na+-dependent activation of TrkG. In addition, we found that TrkG but not TrkH had Na+ uptake activity. Our analysis of K+ transport mutants revealed that TrkH supported cell growth more than TrkG; however, TrkG was able to complement loss of TrkH-mediated K+ uptake in E.coli. Furthermore, we determined that transcription of trkG in E.coli was downregulated but not completely silenced by the xenogeneic silencing factor H-NS (histone-like nucleoid structuring protein or heat-stable nucleoid-structuring protein). Taken together, the transport function of TrkG is clearly distinct from that of TrkH, and TrkG seems to have been accepted by E.coli during evolution as a K+ uptake system that coexists with TrkH.

The R2R3-MYB transcription factor ThRAX2 recognized a new element MYB-T (CTTCCA) to enhance cadmium tolerance in Tamarix hispida

R2R3-MYB transcription factors play an important role in plant development and response to various environmental stresses. In this study, a new R2R3-MYB gene, named ThRAX2, was isolated from T. hispida. ThRAX2 has an open reading frame (ORF) of 1191 bp and encodes a protein of 396 amino acids. ThRAX2 was localized in the nucleus. The overexpression of ThRAX2 in Arabidopsis and T. hispida significantly increased Cadmium (Cd) tolerance. Moreover, the accumulation of cadmium in roots and leaves was significantly reduced. The TF-centred Y1H and Y1H results showed that ThRAX2 was able to specifically bind a new cis-element (MYB-T, CTTCCA). The promoters of some Cd-responsive genes, such as ThSOS1, ThCKX3, ThCAX3A, ThMYB78, ThMIP2, ThTPS4, and ThSOD2, all contained 1–3 MYB-T sequences. Furthermore, chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) and ChIPquantitative (q)PCR showed that the ThRAX2 gene can bind to ThSOS1, ThCKX3, ThCAX3A and ThMYB78 promoter fragments, including the MYB-T motif. Meanwhile, the qRTPCR results also showed that the expression trends of ThSOS1, ThCKX3, ThCAX3A and ThMYB78 were similar to that of ThRAX2. This finding suggests that Cd tolerance of the ThRAX2 gene may regulate the expression of some downstream genes through specific recognition of the MYB-T motif and participate in regulating intracellular ion homeostasis, transport, and protein activity or enhance antioxidant enzyme activity. This study found a novel cis-acting element that binds ThRAX2 to regulate Cd tolerance, which lays the foundation for the ThRAX2 regulatory mechanism of Cd stress. This study provides a genetic and theoretical basis for the bioremediation of Cd-contaminated land by cultivating transgenic plants in the future.

Systematic Investigation of the Diagnostic and Prognostic Impact of LINC01087 in Human Cancers.

(1) Background: Long non-coding RNAs may constitute epigenetic biomarkers for the diagnosis, prognosis, and therapeutic response of a variety of tumors. In this context, we aimed at assessing the diagnostic and prognostic value of the recently described long intergenic non-coding RNA 01087 (LINC01087) in human cancers. (2) Methods: We studied the expression of LINC01087 across 30 oncological indications by interrogating public resources. Data extracted from the TCGA and GTEx databases were exploited to plot receiver operating characteristic curves (ROC) and determine the diagnostic performance of LINC01087. Survival data from TCGA and KM-Plotter directories allowed us to graph Kaplan-Meier curves and evaluate the prognostic value of LINC01087. To investigate the function of LINC01087, gene ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed. Furthermore, interactions between LINC01087 and both miRNA and mRNA were studied by means of bioinformatics tools. (3) Results: LINC01087 was significantly deregulated in 7 out of 30 cancers, showing a predominant upregulation. Notably, it was overexpressed in breast (BC), esophageal (ESCA), and ovarian (OV) cancers, as well as lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD), and uterine carcinosarcoma (UCS). By contrast, LINC01087 displayed downregulation in testicular germ cell tumors (TGCT). ROC curve analyses identified LINC01087 as a potential diagnostic indicator in BC, ESCA, OV, STAD, and TGCT. Moreover, high and low expression of LINC01087 predicted a favorable prognosis in BC and papillary cell carcinoma, respectively. In silico analyses indicated that deregulation of LINC01087 in cancer was associated with a modulation of genes related to ion channel, transporter, and peptide receptor activity. (4) Conclusions: the quantification of an altered abundance of LINC01087 in tissue specimens might be clinically useful for the diagnosis and prognosis of some hormone-related tumors, including BC, OV, and TGCT, as well as other cancer types such as ESCA and STAD. Moreover, our study revealed the potential of LINC01087 (and perhaps other lncRNAs) to regulate neuroactive molecules in cancer.

Fluorescent magnetic chitosan-based hydrogel incorporating Amino-Functionalized Fe3O4 and cellulose nanofibers modified with carbon dots for adsorption and detection of Cr (VI)

A fluorescent magnetic chitosan-based hydrogel (FMCH) incorporating Amino-Functionalized Fe3O4 nanoparticles (AF-Fe3O4 NPs) and cellulose nanofibers (CNFs) modified with carbon dots (CDs) was successfully synthesized via the crosslinking method. The FMCH was used as an adsorbent for removing Cr (VI) from aqueous solution and it exhibited encouraging adsorption performance for Cr (VI). The composition and structure of FMCH were characterized and its Cr (VI) sorption performance was evaluated. The results demonstrated that this hydrogel had 3D porous structures and a higher adsorption ability of Cr (VI). The maximum adsorption capacity of this hydrogel was measured to be 212.1 mg/g at 25 °C and pH 5.0. The performance of the FMCH in Cr (VI) adsorption was evaluated through a contrast experiment with the normal chitosan hydrogel without CNFs and AF-Fe3O4 NPs. The effect of the initial concentration of Cr (VI) and contact time were also evaluated. The results confirmed that the adsorption isotherm was according to the Freundlich model, and the adsorption kinetics followed the pseudo-second-order model. Furthermore, as a fluorescent sensor for Cr (VI), the detection sensitivity and selectivity were examined. The quantitative detection of Cr (VI) was achieved in the linear range of 20–800 mg/L. Meantime, the mechanism for highly efficient adsorption and detection of FMCH for Cr (VI) was analysed by FTIR and XPS. These results showed that the excellent sorption and sensing abilities of Cr (VI) may be mainly attributed to the porous structures which provided many active sites and ion transport channels and the additional AF-Fe3O4 NPs and CNFs modified with CDs improving the sorption ability of Cr (VI) and providing a rapid visual response to Cr (VI). It showed that the FMCH can be widely used for Cr (VI) detection and removal in wastewater.

Genome-Wide In Silico Identification, Structural Analysis, Promoter Analysis, and Expression Profiling of PHT Gene Family in Sugarcane Root under Salinity Stress

The phosphate transporter (PHT) family of proteins plays an imperative role in regulating phosphorus (P) acquisition as well as in translocation from the soil into cells and organs. Phosphorus is an essential macronutrient required for plant life that is not readily available to crops, and resources are diminishing rapidly because of the huge needs of global agriculture. In this study, 23 ShPHT genes were identified in the sugarcane (Saccharum spp.) genome through a comprehensive genome-wide in silico analysis. Phylogeny, gene structure, and conserved motif analysis of PHT genes in sugarcane (ShPHTs) indicated five subfamilies (PHT1-4 and PHO1 subfamily). Gene ontology (GO) analysis revealed that the ShPHT genes were largely involved in phosphate ion transport, phosphate starvation, stimulus response, stress response, and symporter activity. Gene expression analysis under salinity stress confirmed strong induction of PHT genes in wild genotype sugarcane (IND99-907). PHT1-1, PHT1-2, and PHT1-3 members were notably up-regulated in roots under salt stress. The upstream region of PHT genes contained PHR1-binding sites (P1BS), MYB-type, and WRKY- type binding elements. Overall, the present study paves the way for a deeper understanding of the evolution of sugarcane PHT genes and their role in salinity and Pi stress tolerance in sugarcane.

Effect of doping with different sulphur group elements on the performance of silver ion-conducting glass

Ion-conducting glasses of AgI-based Ge-Ga-S, Ge-Ga-Se and Ge-Ga-Te with different sulphur group elements were prepared by melt quenching technique. The electrical properties and thermodynamic stability were investigated and compared. Glass transition temperatures and crystallisation temperatures of the samples were measured using differential scanning calorimetry. Results showed that Ge-Ga-S-AgI had the best thermodynamic stability and glass-forming ability, highest ionic conductivity (1.33 × 10−7 S/cm) at room temperature and lowest conductivity activation energy of 0.41 eV. Raman spectroscopy analysis showed that the [GeInS4-n] (n = 1,2,3) structural units in the S series glasses provided a good environment for the effective transport of Ag+ and formed an active ion transport channel. By contrast, the structural units in the Se and Te series contributed less to the transport of Ag+. This work systematically explored the effects of three elements in the sulphur main group on the performance of Ag+ conductive glasses. This study provides a reference for the rational formulation of sulphur-based Ag+ conductive glass components with enhanced comprehensive properties.

Airway surface hyperviscosity and defective mucociliary transport by IL-17/TNF-α are corrected by β-adrenergic stimulus.

The fluid covering the surface of airway epithelia represents a first barrier against pathogens. The chemical and physical properties of the airway surface fluid are controlled by the activity of ion channels and transporters. In cystic fibrosis (CF), loss of CFTR chloride channel function causes airway surface dehydration, bacterial infection, and inflammation. We investigated the effects of IL-17A plus TNF-α, 2 cytokines with relevant roles in CF and other chronic lung diseases. Transcriptome analysis revealed a profound change with upregulation of several genes involved in ion transport, antibacterial defense, and neutrophil recruitment. At the functional level, bronchial epithelia treated in vitro with the cytokine combination showed upregulation of ENaC channel, ATP12A proton pump, ADRB2 β-adrenergic receptor, and SLC26A4 anion exchanger. The overall result of IL-17A/TNF-α treatment was hyperviscosity of the airway surface, as demonstrated by fluorescence recovery after photobleaching (FRAP) experiments. Importantly, stimulation with a β-adrenergic agonist switched airway surface to a low-viscosity state in non-CF but not in CF epithelia. Our study suggests that CF lung disease is sustained by a vicious cycle in which epithelia cannot exit from the hyperviscous state, thus perpetuating the proinflammatory airway surface condition.

Inhibition of Transforming Growth Factor-β Improves Primary Renal Tubule Cell Differentiation in Long-Term Culture.

Patient-oriented applications of cell culture include cell therapy of organ failure like chronic renal failure. Clinical deployment of a cell-based device for artificial renal replacement requires qualitative and quantitative fidelity of a cultured cell to its in vivo counterpart. Active specific apicobasal ion transport reabsorbs 90-99% of the filtered load of salt and water in the kidney. In a bioengineered kidney, tubular transport concentrates wastes and eliminates the need for hemodialysis, but renal tubule cells in culture transport little or no salt and water due to dedifferentiation that mammalian cells undergo in vitro thereby losing important cell-type specific functions. We previously identified transforming growth factor-β (TGF-β) as a signaling pathway necessary for in vitro differentiation of renal tubule cells. Inhibition of TGF-β receptor-1 led to active and inhibitable electrolyte and water transport by primary human renal tubule epithelial cells in vitro. Addition of metformin increased transport, in the context of a transient effect on 5'-AMP-activated kinase phosphorylation. These data motivated us to examine whether increased transport was an idiosyncratic effect of SB431542, probe pathways downstream of TGF-β receptors possibly responsible for the improved differentiation, evaluate whether TGF-β inhibition induced a range of differentiated tubule functions, and to explore crosstalk between the effects of SB431542 and metformin. In this study, we use multiple small-molecule inhibitors of canonical and noncanonical pathways to confirm that inhibition of canonical TGF-β signaling caused the increased apicobasal transport. Hallmarks of proximal tubule cell function, including sodium reabsorption, para-amino hippurate excretion, and glucose uptake increased with TGF-β inhibition, and the specificity of the response was shown using inhibitors of each transport protein. We did not find any evidence of crosstalk between metformin and SB431542. These data suggest that the TGF-β signaling pathway governs multiple features of differentiation in renal proximal tubule cells in vitro. Inhibition of TGF-β by pharmacologic or genome engineering approaches may be a viable approach to enhancing differentiated function of tubule cells in vitro. Impact statement Cell therapy of renal failure requires qualitative and quantitative fidelity between in vitro and in vivo phenotypes, which has been elusive. We show that control of transforming growth factor-β signaling can promote differentiation of renal tubule cells grown in artificial environments. This is a key enabling step for cell therapy of renal failure.

Breaking the Pump: Targeting the Sodium-Potassium Pump As a Therapeutic Strategy in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogenous hematologic malignancy with poor overall survival despite intensive cytotoxic chemotherapy and newer targeted agents. With a 5-year survival rate of only 30% in adults with AML, new therapeutic strategies are needed. Tissue-specific differences in the expression of paralog genes, which are not essential in most cell types due to the buffering effect of the partner pair, could make for highly selective gene dependencies. To identify novel, selective paralogous targets for AML, we integrated the Cancer Dependency Map, which provides genome-scale CRISPR/Cas9 depletion screening data in hundreds of cancer cell lines, with numerous databases characterizing protein-protein interactions, paralog relationships, and gene expression in cancer models. Here, we identified ATP1B3 as a context-specific, paralog related dependency in AML. ATP1B3 is the smaller glycoprotein beta subunit of the sodium-potassium pump (Na/K-ATP pump). Together with the catalytic alpha subunit ATP1A1, it forms a heterodimer located in the plasma membrane, regulating the electrochemical gradient through the transport of Na and K ions across the membrane. The Na/K-ATP pump is of vital importance in the maintenance of cellular homeostasis and membrane potential. While ATP1A1 carries out the ion transport and enzymatic activity, making it a common essential gene (a gene which ranks among the most depleted genes in at least 90% of screened cell lines), ATP1B3 is not essential in most cancer cells. The beta subunit is important for intracellular transport and stabilization of the alpha subunit in the membrane, but it has three paralogs: ATP1B3 showing similar expression patterns across tissues, ATP1B2 exclusively expressed in brain and retina, and ATP1B1 showing differential expression across tissues. ATP1B1 has uniformly low expression in hematological malignancies and low ATP1B1 expression is the strongest predictor of ATP1B3 dependency (Figure 1). Using CRISPR/Cas9 knockout and competitive growth assays, we showed that knockout of ATP1B3 in ATP1B1 low-expressing AML cells indeed leads to synthetic lethality. Knockout of ATP1B3 significantly decreased number and size of colonies in a patient-derived xenograft (PDX) model of AML to a similar degree as the knockout of the common essential gene ATP1A1. Moreover, in these AML models, the absence of both paralogs of the beta subunit resulted in the destabilization of their binding partner ATP1A1. In contrast, expression of ATP1B1 stabilized ATP1A1 despite ATP1B3 knockout in solid tumors and in ATP1B1-overexpressing AML cells. In vivo, using an orthotopic AML cell line mouse model and an AML PDX model, ATP1B3 knockout resulted in lower leukemia burden in comparison to ATP1B1 knockout or a non-targeting control guide. To determine if ATP1B1 and ATP1B3 share primarily redundant functions, we utilized BioID (proximity-dependent biotin identification) to identify their interaction partners. We discovered that in AML, there is significant overlap of the ATP1B1 and ATP1B3 binding partners, and ATP1A1 is among the strongest. Enrichment of gene sets involved in protein folding in the endoplasmic reticulum are also consistent with the important role of the beta subunits in proper ATP1A1 folding and stabilization. Taken together, we identified ATP1B3 as a selective dependency in AML. We propose that when ATP1B1 is poorly expressed, elimination of ATP1B3 leads to the destabilization of the sodium-potassium pump including ATP1A1. ATP1B3 is a potential tumor-selective therapeutic target for AML and other hematologic malignancies with low expression of ATP1B1. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hypo-Osmoregulatory Roles of Vasotocinergic and Isotocinergic Systems in the Intestines of Two European Sea Bass Lineages.

European sea bass (Dicentrarchus labrax) are a major aquaculture species that live in habitats with fluctuating salinities that are sometimes higher than in seawater (SW). Atlantic and West-Mediterranean genetic lineages were compared regarding intestinal neuropeptide receptor expression in SW (36%) and following a two-week transfer to hypersalinity (HW, 55%). Phylogenetic analysis revealed seven neuropeptide receptors belonging to the arginine vasotocine (AVTR) family and two isotocin receptors (ITR). Among AVTR paralogs, the highest mRNA levels were recorded for v1a2, with a two- to fourfold upregulation in the European sea bass intestinal sections after transfer of fish to HW. Principal component analysis in posterior intestines showed that v1a2 expression grouped together with the expression and activity of main ion transporters and channels involved in solute-coupled water uptake, indicating a possible role of this receptor in triggering water absorption. v1a1 expression, however, was decreased or did not change after transfer to hypersaline water. Among ITR paralogs, itr1 was the most expressed paralog in the intestine and opposite expression patterns were observed following salinity transfer, comparing intestinal sections. Overall, different expression profiles were observed between genetic lineages for several analyzed genes which could contribute to different osmotic stress-related responses in D. labrax lineages.

Structural insights into light-driven anion pumping in cyanobacteria

Transmembrane ion transport is a key process in living cells. Active transport of ions is carried out by various ion transporters including microbial rhodopsins (MRs). MRs perform diverse functions such as active and passive ion transport, photo-sensing, and others. In particular, MRs can pump various monovalent ions like Na+, K+, Cl−, I−, NO3−. The only characterized MR proposed to pump sulfate in addition to halides belongs to the cyanobacterium Synechocystis sp. PCC 7509 and is named Synechocystis halorhodopsin (SyHR). The structural study of SyHR may help to understand what makes an MR pump divalent ions. Here we present the crystal structure of SyHR in the ground state, the structure of its sulfate-bound form as well as two photoreaction intermediates, the K and O states. These data reveal the molecular origin of the unique properties of the protein (exceptionally strong chloride binding and proposed pumping of divalent anions) and sheds light on the mechanism of anion release and uptake in cyanobacterial halorhodopsins. The unique properties of SyHR highlight its potential as an optogenetics tool and may help engineer different types of anion pumps with applications in optogenetics.

Osmotic gradients and transretinal water flow-a quantitative elemental microanalytical study of frozen hydrated chick eyes.

Optical clarity and efficient phototransduction are necessary for optimal vision, however, how the associated processes of osmoregulation and continuous fluid drainage across the whole eye are achieved remains relatively unexplored. Hence, we have employed elemental microanalysis of planed surfaces of light-adapted bulk frozen-hydrated chick eyes to determine the unique intracellular elemental localization, compositions, and hydration states that contribute to maintaining osmotic gradients and water flow from the vitreous, across the retina, retinal pigment epithelium (RPE), to choroid and sclera. As expected, the greatest difference in resultant osmotic concentration gradients, [calculated using the combined concentrations of sodium (Na) and potassium (K)] and tissue hydration [oxygen-defined water concentration], occurs in the outer retina and, in particular, in the RPE where the apical and basal membranes are characterized by numerous bioenergetically active, osmoregulating ion transport mechanisms, aquaporins, and chloride (Cl) channels. Our results also demonstrate that the high intracellular Na+ and K+ concentrations in the apical region of the RPE are partially derived from the melanosomes. The inclusion of the ubiquitous osmolyte taurine to the calculation of the osmotic gradients suggests a more gradual increase in the osmotic transport of water from the vitreous into the ganglion cell layer across the inner retina to the outer segments of the photoreceptor/apical RPE region where the water gradient increases rapidly towards the basal membrane. Thus transretinal water is likely to cross the apical membrane from the retina into the RPE cells down the Na+ and K+ derived osmotic concentration gradient and leave the RPE for the choroid across the basal membrane down the Cl- derived osmotic concentration gradient that is sustained by the well-described bioenergetically active RPE ion transporters and channels.

Investigation of Phosphatidylserine-Transporting Activity of Human TMEM16C Isoforms

Lipid scrambling is a rapid process that dissipates the asymmetrical distribution of phospholipids in the plasma membrane. It is involved in various physiological functions such as blood coagulation and apoptosis. Many TMEM16 members are recognized as Ca2+-activated phospholipid scramblases, which transport phospholipids between the two leaflets of the plasma membrane nonspecifically and bidirectionally; among these, TMEM16C is abundant in the brain, especially in neuronal cells. We investigated the scrambling activity of three human TMEM16C isoforms with different N-terminus lengths. After optimizing conditions to minimize endogenous scrambling activity, an annexin V-based imaging assay was used to detect phosphatidylserine (PS) scrambling in 293T cells. Unlike previous results, our data showed that human TMEM16C isoform 1 and isoform 3 exposed PS to the cell surface. A surface biotinylation assay showed that the surface expression of isoform 2, which did not show scrambling activity, was ~5 times lower than the other isoforms. In contrast to other TMEM16 proteins, flux assays and electrophysiology recording showed TMEM16C does not possess ion-transporting activity. We conclude that the N-terminus of TMEM16C determines whether TMEM16C can translocate to the plasma membrane and facilitate scrambling activity; membrane-localized TMEM16C isoforms 1 and 3 transport PS to the outer leaflet.

Opportunities and Challenges of Black Phosphorus for Electrocatalysis and Rechargeable Batteries

AbstractAs an emerging 2D layered material, black phosphorus (BP) has received intensive attention in recent years, particularly in electrocatalysis and rechargeable batteries. With further structural modifications, BP‐based heterostructured composites have exhibited attractive physical and chemical properties regarding to enhanced conductivity, ion transport, and catalysis activity, endowing them as potential candidates for electrochemical ions storage and electro/chemical catalysis. In this perspective, a brief summary is first given on the recent progress of BP and BP‐derived materials in electrocatalysis, such as hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and nitrogen reduction reaction (NRR), and in rechargeable batteries, such as lithium‐ion batteries (LIBs), sodium‐ion batteries (SIBs), and potassium‐ion batteries (PIBs), followed by a critical review on the current opportunities and challenges. It is expected that this class of emerging materials will bring about new potential solutions to address the current energy crisis and inspire researchers to develop more novel materials toward future multifunctional applications.

Light-driven proton transmembrane transport enabled by bio-semiconductor 2D membrane: A general peptide-induced WS2 band shifting strategy

Light-driven proton directional transport is important in living beings as it could subtly realize the light energy conversion for living uses. In the past years, 2D materials-based nanochannels have shown great potential in active ion transport due to controllable properties, including surface charge distribution, wettability, functionalization, electric structure, and external stimuli responsibility, etc. However, to fuse the inorganic materials into bio-membranes still faces several challenges. Here, we proposed peptide-modified WS2 nanosheets via cysteine linkers to realize tunable band structure and, hence, enable light-driven proton transmembrane transport. The modification was achieved through the thiol chemistry of the –SH groups in the cysteine linker and the S vacancy on the WS2 nanosheets. By tuning the amino residues sequences (lysine-rich peptides, denoted as KFC; and aspartate-rich peptides, denoted as DFC), the ζ-potential, surface charge, and band energy of WS2 nanosheets could be rationally regulated. Janus membranes formed by assembling the peptide-modified WS2 nanosheets could realize the proton transmembrane transport under visible light irradiation, driven by a built-in potential due to a type II band alignment between the KFC-WS2 and DFC-WS2. As a result, the proton would be driven across the formed nanochannels. These results demonstrate a general strategy to build bio-semiconductor materials and provide a new way for embedding inorganic materials into biological systems toward the development of bioelectronic devices.

Comparative analysis of combined phosphorus and drought stress-responses in two winter wheat.

Phosphorus stress and drought stress are common abiotic stresses for wheat. In this study, two winter wheat varieties “Xindong20” and “Xindong23” were cultured in a hydroponic system using Hoagland nutrient solution and treated with drought stress under conventional (CP: 1.0 mmol/L) and low (LP: 0.05 mmol/L) phosphorus levels. Under drought stress, the root growth was better under LP than under CP. Under LP, root phosphorus content was increased by 94.2% in Xindong20 and decreased by 48.9% in Xindong23 at 3 d after re-watering, compared with those at 0 d under drought stress. However, the potassium (K) content was the highest among the four elements studied and the phosphorus (P) and calcium (Ca) content were reduced in the root of the two varieties. Under CP, the zinc (Zn) content was higher than that under LP in Xindong23. The GeneChip analysis showed that a total of 4,577 and 202 differentially expressed genes (DEGs) were detected from the roots of Xindong20 and Xindong23, respectively. Among them, 89.9% of DEGs were involved in organelles and vesicles in Xindong20, and 69.8% were involved in root anatomical structure, respiratory chain, electron transport chain, ion transport, and enzyme activity in Xindong23. Overall, LP was superior to CP in mitigating drought stress on wheat, and the regulatory genes were also different in the two varieties. Xindong20 had higher drought tolerance for more up-regulated genes involved in the responses compared to Xindong23.

Molecular Features of SLC26A4 Common Variant p.L117F.

The SLC26A4 gene, which encodes the anion exchanger pendrin, is involved in determining syndromic (Pendred syndrome) and non-syndromic (DFNB4) autosomal recessive hearing loss. SLC26A4 c.349C>T, p.L117F is a relatively common allele in the Ashkenazi Jewish community, where its minor allele frequency is increased compared to other populations. Although segregation and allelic data support the pathogenicity of this variant, former functional tests showed characteristics that were indistinguishable from those of the wild-type protein. Here, we applied a triad of cell-based assays, i.e., measurement of the ion transport activity by a fluorometric method, determination of the subcellular localization by confocal microscopy, and assessment of protein expression levels, to conclusively assign or exclude the pathogenicity of SLC26A4 p.L117F. This protein variant showed a moderate, but significant, reduction in ion transport function, a partial retention in the endoplasmic reticulum, and a strong reduction in expression levels as a consequence of an accelerated degradation by the Ubiquitin Proteasome System, all supporting pathogenicity. The functional and molecular features of human pendrin p.L117F were recapitulated by the mouse ortholog, thus indicating that a mouse carrying this variant might represent a good model of Pendred syndrome/DFNB4.

Proton-transporting heliorhodopsins from marine giant viruses.

Rhodopsins convert light into signals and energy in animals and microbes. Heliorhodopsins (HeRs), a recently discovered new rhodopsin family, are widely present in archaea, bacteria, unicellular eukaryotes, and giant viruses, but their function remains unknown. Here, we report that a viral HeR from Emiliania huxleyi virus 202 (V2HeR3) is a light-activated proton transporter. V2HeR3 absorbs blue-green light, and the active intermediate contains the deprotonated retinal Schiff base. Site-directed mutagenesis study revealed that E191 in TM6 constitutes the gate together with the retinal Schiff base. E205 and E215 form a PAG of the Schiff base, and mutations at these positions converted the protein into an outward proton pump. Three environmental viral HeRs from the same group as well as a more distantly related HeR exhibited similar proton-transport activity, indicating that HeR functions might be diverse similarly to type-1 microbial rhodopsins. Some strains of E. huxleyi contain one HeR that is related to the viral HeRs, while its viruses EhV-201 and EhV-202 contain two and three HeRs, respectively. Except for V2HeR3 from EhV-202, none of these proteins exhibit ion transport activity. Thus, when expressed in the E. huxleyi cell membranes, only V2HeR3 has the potential to depolarize the host cells by light, possibly to overcome the host defense mechanisms or to prevent superinfection. The neuronal activity generated by V2HeR3 suggests that it can potentially be used as an optogenetic tool, similarly to type-1 microbial rhodopsins.