Regulation Of Ion Transport Research Articles

Circ_0001068 accelerates the development of ovarian cancer by promoting FXYD5 expression through inhibiting mir-149-5p activity.

Ovarian cancer (OC) is one of the common malignancies of the female reproductive organs. Microarray analysis shows that circ_0001068 is upregulated in OC patients, however, its carcinogenic effect on OC development has not yet been revealed. In this study, qRT-PCR and western blotting were used to determine the expression of circ_0001068, microRNA-149-5p (miR-149-5p) and domain containing ion transport regulator 5 (FXYD5). Clone formation was used to assess cell proliferation, and transwell assays were performed to analyze cell migration and invasion. Dual-luciferase reporter and pull down assays were used to verify the binding relationship between circ_0001068 and miR-149-5p or FXYD5. Mouse xenograft tumor formation was performed to validate the role of circ_0001068 in vivo. We found that the expression levels of circ_0001068 and FXYD5 were significantly increased in OC tissues and cell lines. Circ_0001068 knockdown significantly inhibited cell proliferation, migration, invasion, glycolysis, and glutamine metabolism. Circ_0001068 directly interacted with miR-149-5p, and the introduction of miR-149-5p mimics in OC cells partially reversed circ_0001068 knockdown-mediated effects. MiR-149-5p directly interacted with the 3'untranslated region (3'UTR) of FXYD5, and FXYD5 overexpression partially counteracted circ_0001068 knockdown-mediated effects in OC cells. Circ_0001068 knockdown inhibited xenograft tumor growth in vivo. Our findings suggest that circ_0001068 promotes the malignant properties of OC cells by targeting the miR-149-5p/FXYD5 axis.

Regulation of magnesium ion transport in Escherichia coli: insights into the role of the 5’ upstream region in corA expression

ABSTRACT In Escherichia coli, transport of magnesium ions across the cellular membrane relies on MgtA and CorA transporters. While the expression of mgtA is controlled by the two-component system PhoQ/PhoP and 5’ upstream region elements, corA expression is considered to be constitutive and not to depend on cellular factors. Importantly, the 5’ upstream region of corA is predicted to fold into structures highly similar to the magnesium-sensing mgtA 5‘ upstream region. Here using biochemical and genetic assays, we show that the intracellular concentration of magnesium ions affects corA expression. Similarly to mgtA, we find that the effect of magnesium ions on corA expression is mediated by the 5’ upstream region. We demonstrate that the RNA structure is important for regulation and that the Rho transcription factor is involved in the modulation of transcription termination. Consistent with previous studies, we find that translation of corL, a short ORF located within the 5’ upstream region, is important for corA regulation. Our data indicate that the efficiency of corL translation is inversely proportional to corA expression, similar to what has been described for mgtA and corA in Salmonella enterica. Using a novel assay to control the import of magnesium ions, we show that while the expression of mgtA is regulated by both extra- and intracellular magnesium ions, corA is regulated by variations in intracellular magnesium ions. Our results support a model in which the expression of corA is regulated by the 5’ upstream region that senses variations of intracellular magnesium ions.

Wood‐inspired High Ionic Conductivity Hydrogel Electrolytes for Flexible Supercapacitors

Hydrogel is a promising electrolyte substrate, but its ionic conductivity needs further improvement. In this paper, we propose a strategy to improve the ionic conductivity of hydrogels with flexible wood and fabricate a flexible wood‐based poly(acrylic acid‐acrylamide) composite hydrogel electrolyte (WHE) by delignification and in‐situ polymerization. The flexible wood as a porous backbone for hydrogels can regulate ion transport pathways to improve the ionic conductivity of hydrogels. The straight pores of wood confine the transport of electrolyte ions along the shortest path, resulting in a high ionic conductivity of 3.0 × 10‐2 S cm‐1, which is great in composite polymer electrolytes. We have systematically investigated the effect of the degree of delignification and the polymerization process on the overall performance of the electrolyte. The optimized supercapacitor exhibits a specific capacitance of 155.64 F g‐1 and an energy density of 7.45 W h kg‐1. The WHE is applied to flexible supercapacitor, which exhibits good flexibility under bending conditions and can maintain similar electrochemical performance at a wide range of bending angles. This work provides an effective strategy for the efficient use of wood resources and the development of low‐cost, environmentally friendly, and high‐performance hydrogel electrolyte materials.

Alterations in the placental proteome in association with the presence of black carbon particles: A discovery study

BackgroundExposure to ambient air pollution is known to cause direct and indirect molecular expression changes in the placenta, on the DNA, mRNA, and protein levels. Ambient black carbon (BC) particles can be found in the human placenta already very early in gestation. However, the effect of in utero BC exposure on the entire placental proteome has never been studied to date. ObjectivesWe explored whether placental proteome differs between mothers exposed to either high or low BC levels throughout the entire pregnancy. MethodsWe used placental tissue samples from the ENVIRONAGE birth cohort, of 20 non-smoking, maternal- and neonate characteristic-matched women exposed to high (n = 10) or low (n = 10) levels of ambient BC throughout pregnancy. We modeled prenatal BC exposure levels based on the mother's home address and measured BC levels in the fetal side of the placenta. The placental proteome was analyzed by nano-liquid chromatography Q-TOF mass spectrometry. PEAKS software was used for protein identification and label-free quantification. Protein-protein interaction and functional pathway enrichment analyses were performed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software. ResultsThe accumulation of BC particles in placenta was 2.19 times higher in the high versus low exposure group (20943.4 vs 9542.7 particles/mm³; p = 0.007). Thirteen proteins showed a ≥2-fold expression difference between the two exposure groups, all overexpressed in the placentas of women prenatally exposed to high BC levels. Three protein-protein interactions were enriched within this group, namely between TIMP3 and COL4A2, SERPINE2 and COL4A2, and SERPINE2 and GP1BB. Functional pathway enrichment analysis put forward pathways involved in extracellular matrix-receptor interaction, fibrin clot formation, and sodium ion transport regulation. DiscussionPrenatal BC exposure affects the placental proteome. Future research should focus on the potential consequences of these alterations on placental functioning, and health and disease during early childhood development.

Cakile maritima: A Halophyte Model to Study Salt Tolerance Mechanisms and Potential Useful Crop for Sustainable Saline Agriculture in the Context of Climate Change.

Salinity is an increasing problem for agriculture. Most plant species tolerate low or, at best, moderate soil salinities. However, a small (<1%) proportion of species, termed halophytes, can survive and complete their life cycle in natural habitats with salinities equivalent to 200 mM NaCl or more. Cakile maritima is a succulent annual halophyte belonging to the Brassicaceae family; it is dispersed worldwide and mainly grows in foreshores. Cakile maritima growth is optimal under slight (i.e., 100 mM NaCl) saline conditions, measured by biomass and seed production. Higher salt concentrations, up to 500 mM NaCl, significantly impact its growth but do not compromise its survival. Cakile maritima alleviates sodium toxicity through different strategies, including anatomical and morphological adaptations, ion transport regulation, biosynthesis of osmolytes, and activation of antioxidative mechanisms. The species is potentially useful as a cash crop for the so-called biosaline agriculture due to its production of secondary metabolites of medical and nutritional interest and the high oil accumulation in its seeds. In this review, we highlight the relevance of this species as a model for studying the basic mechanisms of salt tolerance and for sustainable biosaline agriculture in the context of soil salination and climate change.

Porous Organic Cage-Based Quasi-Solid-State Electrolyte with Cavity-Induced Anion-Trapping Effect for Long-Life Lithium Metal Batteries

Porous organic cages (POCs) with permanent porosity and excellent host–guest property hold great potentials in regulating ion transport behavior, yet their feasibility as solid-state electrolytes has never been testified in a practical battery. Herein, we design and fabricate a quasi-solid-state electrolyte (QSSE) based on a POC to enable the stable operation of Li-metal batteries (LMBs). Benefiting from the ordered channels and cavity-induced anion-trapping effect of POC, the resulting POC-based QSSE exhibits a high Li+ transference number of 0.67 and a high ionic conductivity of 1.25 × 10−4 S cm−1 with a low activation energy of 0.17 eV. These allow for homogeneous Li deposition and highly reversible Li plating/stripping for over 2000 h. As a proof of concept, the LMB assembled with POC-based QSSE demonstrates extremely stable cycling performance with 85% capacity retention after 1000 cycles. Therefore, our work demonstrates the practical applicability of POC as SSEs for LMBs and could be extended to other energy-storage systems, such as Na and K batteries.

9246 Mineralocorticoid Receptor Regulation of the Molecular Clock in Cardiomyocytes Is Modulated by Time of Day

Abstract Disclosure: M. Kanki: None. S. Heanue: None. P.J. Fuller: None. T.J. Cole: None. C.D. Clyne: None. M.J. Young: None. The onset of cardiovascular disease events peaks in the early morning, which coincides with the diurnal surge in aldosterone and cortisol. Aldosterone-induced mineralocorticoid receptor (MR) activation in cardiomyocytes has established roles in cardiac pump function and electrophysiology and inappropriate MR activation promotes cardiovascular pathophysiology in experimental models of hypertension and heart failure and in the clinic. Recently, we identified a novel role for MR in regulating the circadian clock signalling network in cardiac cells and showed that time of day modulates MR activation in the heart. Whether time-of-day-dependent MR regulation of circadian clocks in cardiomyocytes modulates temporal expression of key functional pathways is unknown. Therefore, we sought to identify cardiac responsiveness to MR stimulation at lights on (7AM) versus lights off (7PM) in ≥8-week old male wildtype (WT) and cardiomyocyte-MR knockout (MyoMRKO) mice. RNA-seq analyses revealed that aldosterone (50 ug/kg) administered at 7PM but not at 7AM significantly enriched transcription of genes associated with 52 biological processes including “Circadian rhythm”, “Reg. of blood pressure”, “Ion transport” and “Reg. of the force of heart contraction” in WT hearts (p&amp;lt;0.05 versus 7PM vehicle-injected WT mice). These outcomes were absent in hearts isolated from MyoMRKO mice administered aldosterone at 7AM or 7PM. Analysis by RT-qPCR revealed that aldosterone versus vehicle administered at 7AM increased expression of circadian Period (Per) and Thyrotroph embryonic factor (Tef) genes in WT hearts, which was lost in MyoMRKO mice. Whole transcriptome analysis also detected significant enrichment in “Cell-cell signalling”, “Positive regulation of cell differentiation”, “Positive regulation of glucose metabolic process”, “Regulation of sodium ion transport”, and “Inflammatory response" processes between 7AM and 7PM in WT hearts, which was also lost in MyoMRKO mice. Our data show that MR transcription of genes associated with circadian rhythms and ion transport is temporally regulated, and demonstrates specificity for cardiomyocyte-MR regulation of circadian clocks. Taken together, we highlight that the role for cardiomyocyte-MR regulation of cardiac electrophysiology, heart rate variability, and metabolic processes is time-of-day-dependent. Understanding temporal coordination of MR activation in physiology and pathophysiology may inform new strategies for optimising MR-directed therapies in patients with heart disease. Presentation: 6/2/2024

7763 Mineralocorticoid Receptor Regulation of the Molecular Clock in Cardiomyocytes Is Modulated by Time of Day

Abstract Disclosure: M. Kanki: None. S. Heanue: None. P.J. Fuller: None. T.J. Cole: None. C.D. Clyne: None. M.J. Young: None. The onset of cardiovascular disease events peaks in the early morning, which coincides with the diurnal surge in aldosterone and cortisol. Aldosterone-induced mineralocorticoid receptor (MR) activation in cardiomyocytes has established roles in cardiac pump function and electrophysiology and inappropriate MR activation promotes cardiovascular pathophysiology in experimental models of hypertension and heart failure and in the clinic. Recently, we identified a novel role for MR in regulating the circadian clock signalling network in cardiac cells and showed that time of day modulates MR activation in the heart. Whether time-of-day-dependent MR regulation of circadian clocks in cardiomyocytes modulates temporal expression of key functional pathways is unknown. Therefore, we sought to identify cardiac responsiveness to MR stimulation at lights on (7AM) versus lights off (7PM) in ≥8-week old male wildtype (WT) and cardiomyocyte-MR knockout (MyoMRKO) mice. RNA-seq analyses revealed that aldosterone (50 ug/kg) administered at 7PM but not at 7AM significantly enriched transcription of genes associated with 52 biological processes including “Circadian rhythm”, “Reg. of blood pressure”, “Ion transport” and “Reg. of the force of heart contraction” in WT hearts (p&amp;lt;0.05 versus 7PM vehicle-injected WT mice). These outcomes were absent in hearts isolated from MyoMRKO mice administered aldosterone at 7AM or 7PM. Analysis by RT-qPCR revealed that aldosterone versus vehicle administered at 7AM increased expression of circadian Period (Per) and Thyrotroph embryonic factor (Tef) genes in WT hearts, which was lost in MyoMRKO mice. Whole transcriptome analysis also detected significant enrichment in “Cell-cell signalling”, “Positive regulation of cell differentiation”, “Positive regulation of glucose metabolic process”, “Regulation of sodium ion transport”, and “Inflammatory response" processes between 7AM and 7PM in WT hearts, which was also lost in MyoMRKO mice. Our data show that MR transcription of genes associated with circadian rhythms and ion transport is temporally regulated, and demonstrates specificity for cardiomyocyte-MR regulation of circadian clocks. Taken together, we highlight that the role for cardiomyocyte-MR regulation of cardiac electrophysiology, heart rate variability, and metabolic processes is time-of-day-dependent. Understanding temporal coordination of MR activation in physiology and pathophysiology may inform new strategies for optimising MR-directed therapies in patients with heart disease. Presentation: 6/2/2024

Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans-Partial revision of our current knowledge required.

Appropriate composition of oral saliva is essential for a healthy milieu that protects mucosa and teeth. Only few studies, with small sample numbers, investigated physiological saliva ion composition in humans. We determined saliva ion composition in a sufficiently large cohort of healthy adults and analyzed the effect of physiological stimulation. We collected saliva from 102 adults under non-stimulated and physiologically stimulated conditions (chewing). Individual flow rates, pH, osmolality, Na+, K+, Cl-, and HCO3- concentrations under both conditions as well as the individual changes due to stimulation (Δvalues) were determined. Non-stimulated saliva was hypoosmolal and acidic. Na+, Cl-, and HCO3- concentrations remained well below physiological plasma values, whereas K+ concentrations exceeded plasma values more than twofold. Stimulation resulted in a doubling of flow rates and substantial increases in pH, HCO3-, and Na+ concentrations. Overall, stimulation did not considerably affect osmolality nor K+ or Cl- concentrations of saliva. An in-depth analysis of stimulation effects, using individual Δvalues, showed no correlation of Δflow rate with Δion concentrations, indicating independent regulation of acinar volume and ductal ion transport. Stimulation-induced Δ[Na+] correlated with Δ[HCO3-] and Δ[Cl-] but not with Δ[K+], indicating common regulation of ductal Na+, Cl-, and HCO3- transport. We present a robust data set of human oral saliva ion composition in healthy adults and functional insights into physiological stimulation. Our data show (i) that flow-dependence exists for Na+ and HCO3- but not for K+ and Cl- concentrations, (ii) osmolality is flow-independent, (iii) regulation of Na+, Cl-, and HCO3- transport is coupled, (iv) regulation of flow rate and ion concentrations are independent and (v) spatially separated between acini and ducts, respectively.

Transcriptomic Profiling of Human Myocardium at Sudden Death to DefineVulnerable Substrate for LethalArrhythmias.

While some chronic pathological substrates for sudden cardiac death (SCD) are well known (eg, coronary artery disease and left ventricular [LV] dysfunction), the acute vulnerable myocardial state predisposing to fatal arrhythmia remains a critical barrier to near-term SCD prevention. This study sought to define the distinct myocardial transcriptomic profile of autopsy-defined arrhythmic sudden deaths, compared to nonarrhythmic sudden deaths and trauma deaths, to determine the acute vulnerable state in the hours to days before SCD. We used autopsy to adjudicate arrhythmic from nonarrhythmic causes in 1,265 sudden deaths in San Francisco County from 2011 to 2018. We performed a degradation-tolerant transcriptomic evaluation of LVs sampled at the time of SCD from 245 consented cases using a curated panel of 448 gene probes with known or hypothesized association with SCD. The targeted transcriptome of arrhythmic (n = 129) vs nonarrhythmic (n=90 nonarrhythmic sudden deaths+ 26 trauma deaths) LV samples revealed 31 differentially up-regulated and 36 down-regulated genes (adjusted P< 0.05) related to the collagen-containing extracellular matrix (up-regulation of FAP, FMOD, and LTBP2), regulation of ion transport (up-regulation of KCNA5 and KCNN3 and down-regulation of KCNJ8, KCNK1, and KCNJ5), and contraction (down-regulation of MYH6). Fibrosis-related genes showed the highest magnitude increased expression in arrhythmic vs nonarrhythmic deaths and vs published transcriptomes from end-stage heart failure. After molecular stratification by known markers for mature (COL1A1, COL1A2, COL3A1) and active (POSTN, MEOX1) fibrosis, cases with the highest expression of both had the largest proportion of arrhythmic cause of death (n=27 of 36 [75%]) vs cases with low expression of both markers (n=87 of 181 [38%]) (P = 0.006) or vs mature only (n=10 of 14 [71%]) or active only (n=5 of 14 [36%]). Activated fibroblast gene expression signature was enriched in arrhythmic female vs arrhythmic male cases, among other sex-specific differences in ion-channel and myosin (up-regulation of SCN4B, SCN8A, and KCNAB1 in females and KCNJ4 and MYH7B in males) expression. RNA profiling of the myocardium at SCD identifies active fibrosis, undetectable by conventional clinical methods, in the presence of fixed scar and selected ion-channel dysregulation (more pronounced among female cases) as an acute vulnerable substrate for fatal arrhythmias. These findings may represent novel directions to identify patients at elevated near-term risk for SCD and critical pathways for intervention to reduce acute lethal arrhythmias.

Investigating the generation mechanism of nanobubbles and the ion-transport regulation on nanofiltration membranes for efficient salt-salt separation

Nanofoaming-assisted interfacial polymerization (IP) exhibits strong potential to regulate the structure and the separation performance of thin film composite (TFC) membranes. At present, it is recognized that when NaHCO3 is employed as an aqueous foaming agent, the generation of nanobubbles is ascribed to the NaHCO3 acidification and may be enhanced by increasing the NaHCO3 dosage. However, to more accurately measure the generation of nanobubbles, it is necessary to analyze the content and composition of carbonates in the aqueous solution at the initial and final states of interfacial polymerization, which is currently lacking in research. In this work, based on the chemical equilibrium theory, the aqueous carbonate chemistry and the quantity of CO2 released during IP was evaluated through monitoring the pH changes near the interface and calculating the carbonate distribution fraction. Results showed that the pH of the aqueous solution changed from 10.3∼11.4 to 6.0∼6.5 during interfacial polymerization when the NaHCO3 dosage was 0.00∼0.10 wt%. However, this variation in pH was subtle (from ∼9.3 to ∼8.8) when 1.00 wt% NaHCO3 was added, leading to limited transformation of carbonate into H2CO3 and, consequently, less generation of CO2. In the whole dosage range of NaHCO3, 0.10 wt% NaHCO3 contributed to the maximum quantity of CO2 during IP, which was also confirmed by the vesicle-like membrane morphology. The resultant membrane achieved a superior salt-salt separation, with selectivity for Mg2+ and Li+/Na+/K+ enhancements of more than 2 times compared to the membrane without NaHCO3 dosage. This work proposed a new approach to evaluate the inner relationship between NaHCO3 dosage and nanobubble quantity during IP, which provides an ion-transport regulation mechanism of nanofiltration membranes for efficient salt-salt separation.

Covalent Organic Frameworks Interfacial Modification of Ceramic Electrolytes for Enhanced Electrochemical Performance

AbstractThe interface instability between inorganic ceramic electrolytes and lithium metal anodes seriously affects the cycling behavior of high‐performance lithium‐metal batteries. Herein, an in situ interfacial modification strategy is proposed to build the precise hybrid organic/inorganic lithium‐ion conducting layer where the Li1.3Al0.3Ti1.7(PO4)3 (LATP) particle surface is anchored by ion‐conducting covalent organic frameworks (COF) with affluent poly(ethylene glycol) (PEG) moieties. This interlayer features ion transport regulation to avoid high interfacial resistance and enhances interfacial stability by building a functional COF‐based shield against electrons. These as‐prepared particles are employed to fabricate flexible quasi‐solid electrolyte membranes interconnected by polytetrafluoroethylene binder based on the dry process. The obtained membranes perform two‐fold increase in ion conductivity at 30 °C of 2.55 × 10−3 S cm−1 and the prolonged lithium deposition up to 1000 h compared to the pristine, which are attributed to synergistic effects in the inorganic/organic phase. Moreover, an integrated cathode/electrolytes design is proposed and exhibits excellent cycling performance with capacity retention of 98.8% after 200 cycles at 1 C. The corresponding pouch cells can light up LED after bending and recovery. This research provides new insights into the great potential of fabricating soft ceramic‐based membranes in a low‐cost and green way for highly‐stable lithium‐metal batteries.

The Microphthalmia-Associated Transcription Factor (MITF) and Its Role in the Structure and Function of the Eye.

The microphthalmia-associated transcription factor (Mitf) has been found to play an important role in eye development, structure, and function. The Mitf gene is responsible for controlling cellular processes in a range of cell types, contributing to multiple eye development processes. In this review, we survey what is now known about the impact of Mitf on eye structure and function in retinal disorders. Several mutations in the human and mouse Mitf gene are now known, and the effects of these on eye phenotype are addressed. We discuss the importance of Mitf in regulating ion transport across the retinal pigment epithelium (RPE) and the vasculature of the eye. The literature was searched using the PubMed, Scopus, and Google Scholar databases. Fundus and Optical Coherence Tomography (OCT) images from mice were obtained with a Micron IV rodent imaging system. Defects in neural-crest-derived melanocytes resulting from any Mitf mutations lead to hypopigmentation in the eye, coat, and inner functioning of the animals. While many Mitf mutations target RPE cells in the eye, fewer impact osteoclasts at the same time. Some of the mutations in mice lead to microphthalmia, and ultimately vision loss, while other mice show a normal eye size; however, the latter, in some cases, show hypopigmentation in the fundus and the choroid is depigmented and thickened, and in rare cases Mitf mutations lead to progressive retinal degeneration. The Mitf gene has an impact on the structure and function of the retina and its vasculature, the RPE, and the choroid in the adult eye.

Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions

Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)–dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. Statement of significancePeritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.

Site-Specific Location of Black Phosphorus Quantum Dot Cluster-Based Nanocomplexes for Synergistic Ion Channel Therapy and Hypoxic Microenvironment Activated Chemotherapy.

The spatiotemporal regulation of ion transport in living cell membrane channels has immense potential for providing novel therapeutic approaches for the treatment of currently intractable diseases. So far, most strategies suffer from uncontrolled ion transport and limited tumor therapy effects. On the premise of low toxicity to healthy tissues, enhancing the degree of ion overloading and the effect of tumor treatment still remains a challenging concern. Herein, an innovative strategy for synergistic ion channel therapy and hypoxic microenvironment activated chemotherapy is proposed. Biocompatible AQ4N/black phosphorus quantum dot clusters@liposomes (AQ4N/BPCs@Lip) nanocomplexes are site-specifically immobilized on the living cell membrane by a metabolic labeling strategy, eliminating the need for modifying or genetically encoding channel structures. Ascribing to the localized temperature increase of BPCs under NIR light irradiation, Ca2+ overinflux can be remotely controlled and the overloading degree was increased; moreover, the local released AQ4N can only be activated in the tumor cell, while it has no toxicity to normal cells. Compared with single intracellular Ca2+ overloading, the tumor cell viabilities decrease 2-fold with synergetic Ca2+ overloading-induced ion channel therapy and hypoxic microenvironment activated chemotherapeutics. Our study demonstrates the example of a remote-controlled ion influx and drug delivery system for tumor therapy.

Zein protein-functionalized separator through a viable method for trapping polysulfides and regulating ion transport in Li[sbnd]S batteries

Commercialization of lithium‑sulfur (LiS) batteries as a promising energy storage system, is primarily impeded by polysulfide shuttling and uncontrollable lithium dendrite growth. To address the issues for improving the performance of LiS batteries, we decorate the separator with zein (corn protein) via a simple soaking process. Owing to strong zein–polysulfide interactions, the zein-soaked separator effectively enhances the polysulfide-trapping capability. Moreover, abundant functional groups of zein also stabilize Li-ion deposition, and thus suppresses the growth of Li dendrites. As a result, the resulting LiS batteries exhibited enhanced electrochemical performance in terms of cycling stability, capacity retention, and rate capability. The soaking method used for coating zein on pristine separator offers a scalable solution for generating multifunctional separators toward commercialization.

Differential expression of ion channel coding genes in the endometrium of women experiencing recurrent implantation failures

Our study probed the differences in ion channel gene expression in the endometrium of women with Recurrent Implantation Failure (RIF) compared to fertile women. We analyzed the relative expression of genes coding for T-type Ca2+, ENaC, CFTR, and KCNQ1 channels in endometrial samples from 20 RIF-affected and 10 control women, aged 22–35, via microarray analysis and quantitative real-time PCR. Additionally, we examined DNA methylation in the regulatory region of KCNQ1 using ChIP real-time PCR. The bioinformatics component of our research included Gene Ontology analysis, protein–protein interaction networks, and signaling pathway mapping to identify key biological processes and pathways implicated in RIF. This led to the discovery of significant alterations in the expression of ion channel genes in RIF women’s endometrium, most notably an overexpression of CFTR and reduced expression of SCNN1A, SCNN1B, SCNN1G, CACNA1H, and KCNQ1. A higher DNA methylation level of KCNQ1’s regulatory region was also observed in RIF patients. Gene-set enrichment analysis highlighted a significant presence of genes involved with ion transport and membrane potential regulation, particularly in sodium and calcium channel complexes, which are vital for cation movement across cell membranes. Genes were also enriched in broader ion channel and transmembrane transporter complexes, underscoring their potential extensive role in cellular ion homeostasis and signaling. These findings suggest a potential involvement of ion channels in the pathology of implantation failure, offering new insights into the mechanisms behind RIF and possible therapeutic targets.

With No Lysine (K) Kinases and Sodium Transporter Function in Solute Exchange with Implications for BP Regulation as Elucidated through Drosophila.

Like other multicellular organisms, the fruit fly Drosophila melanogaster must maintain homeostasis of the internal milieu, including the maintenance of constant ion and water concentrations. In mammals, the with no lysine (K) (WNK)-Ste20-proline/alanine rich kinase/oxidative stress response 1 kinase cascade is an important regulator of epithelial ion transport in the kidney. This pathway regulates SLC12 family cotransporters, including sodium-potassium-2-chloride, sodium chloride, and potassium chloride cotransporters. The WNK-Ste20-proline/alanine rich kinase/oxidative stress response 1 kinase cascade also regulates epithelial ion transport via regulation of the Drosophila sodium-potassium-2-chloride cotransporter in the Malpighian tubule, the renal epithelium of the fly. Studies in Drosophila have contributed to the understanding of multiple regulators of WNK pathway signaling, including intracellular chloride and potassium, the scaffold protein Mo25, hypertonic stress, hydrostatic pressure, and macromolecular crowding. These will be discussed together, with implications for mammalian kidney function and BP control.

MiRNA Sequencing Analysis in Maize Roots Treated with Neutral and Alkaline Salts.

Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize's salt-alkali tolerance.

Fast-Kinetics Electrochemcial Charge Storage by 2D Layered Materials

Electrochemical energy storage technologies have garnered significant attention due to their efficient and sophisticated approaches for storing, transporting, and supplying energy derived from sustainable resources.[1-2] The demand for power and energy supply is crucial in practical applications and is poised to expand further in the future. Hence, there is a pressing need to either design new electrode materials or intelligently reconstruct existing ones for energy storage devices to address the power-energy tradeoff effectively. In this presentation, I will highlight our recent endeavors in the exploration of 2D layered materials for sustainable energy storage applications.[3] Specifically, I will outline various interlayer engineering strategies developed for inorganic 2D layered materials. These strategies aim to regulate ion transport behaviors and enhance the power-energy performance of the assembled energy storage devices.[4-7]