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1.
BMC Plant Biol ; 24(1): 372, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714917

RESUMEN

BACKGROUND: High-affinity potassium transporters (HKTs) are crucial in facilitating potassium uptake by plants. Many types of HKTs confer salt tolerance to plants through regulating K+ and Na+ homeostasis under salinity stress. However, their specific functions in cassava (Manihot esculenta) remain unclear. RESULTS: Herein, an HKT gene (MeHKT1) was cloned from cassava, and its expression is triggered by exposure to salt stress. The expression of a plasma membrane-bound protein functions as transporter to rescue a low potassium (K+) sensitivity of yeast mutant strain, but the complementation of MeHKT1 is inhibited by NaCl treatment. Under low K+ stress, transgenic Arabidopsis with MeHKT1 exhibits improved growth due to increasing shoot K+ content. In contrast, transgenic Arabidopsis accumulates more Na+ under salt stress than wild-type (WT) plants. Nevertheless, the differences in K+ content between transgenic and WT plants are not significant. Additionally, Arabidopsis expressing MeHKT1 displayed a stronger salt-sensitive phenotype. CONCLUSION: These results suggest that under low K+ condition, MeHKT1 functions as a potassium transporter. In contrast, MeHKT1 mainly transports Na+ into cells under salt stress condition and negatively regulates the response of transgenic Arabidopsis to salt stress. Our results provide a reference for further research on the function of MeHKT1, and provide a basis for further application of MeHKT1 in cassava by molecular biological means.


Asunto(s)
Arabidopsis , Manihot , Proteínas de Plantas , Plantas Modificadas Genéticamente , Potasio , Estrés Salino , Arabidopsis/genética , Arabidopsis/fisiología , Arabidopsis/metabolismo , Manihot/genética , Manihot/metabolismo , Manihot/fisiología , Plantas Modificadas Genéticamente/genética , Potasio/metabolismo , Estrés Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Regulación de la Expresión Génica de las Plantas , Tolerancia a la Sal/genética , Sodio/metabolismo
2.
Nat Commun ; 15(1): 3850, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719864

RESUMEN

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.


Asunto(s)
Adenosina Difosfato , Adenosina Trifosfato , Bacillus subtilis , Proteínas Bacterianas , Potasio , Sodio , Adenosina Trifosfato/metabolismo , Bacillus subtilis/metabolismo , Sodio/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Potasio/metabolismo , Cristalografía por Rayos X , Adenosina Difosfato/metabolismo , Microscopía por Crioelectrón , Sitios de Unión , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/química , Modelos Moleculares , Unión Proteica
3.
J Am Chem Soc ; 146(19): 13588-13597, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38695646

RESUMEN

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.


Asunto(s)
Líquidos Iónicos , Simulación de Dinámica Molecular , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Humanos , Acuaporina 2/metabolismo , Acuaporina 2/química , Agua/química , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Sodio/química , Sodio/metabolismo
4.
Anal Chim Acta ; 1308: 342661, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38740461

RESUMEN

BACKGROUND: Timely diagnosis and prevention of diseases require rapid and sensitive detection of biomarkers from blood samples without external interference. Abnormal electrolyte ion levels in the blood are closely linked to various physiological disorders, including hypertension. Therefore, accurate, interference-free, and precise measurement of electrolyte ion concentrations in the blood is particularly important. RESULTS: In this work, a colorimetric sensor based on a biphasic microdroplet extraction is proposed for the detection of electrolyte ions in the blood. This sensor employs mini-pillar arrays to facilitate contact between adjacent blood microdroplets and organic microdroplets serving as sensing phases, with any color changes being monitored through a smartphone's colorimetric software. The sensor is highly resistant to interference and does not require pre-treatment of the blood samples. Remarkably, the sensor exhibits exceptional reliability and stability, allowing for rapid enrichment and detection of K+, Na+, and Cl- in the blood within 10 s (Cl-), 15 s (K+) and 40 s (Na+) respectively. SIGNIFICANCE: The colorimetric sensor based on biphasic microdroplet extraction offers portability due to its compact size and ease of operation without the need for large instruments. Additionally, it is location-independent, making it a promising tool for real-time biomarker detection in body fluids such as blood.


Asunto(s)
Colorimetría , Electrólitos , Potasio , Colorimetría/métodos , Electrólitos/química , Humanos , Potasio/sangre , Sodio/sangre , Cloruros/sangre , Iones/química
5.
Nat Commun ; 15(1): 4277, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769288

RESUMEN

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.


Asunto(s)
Mitocondrias Cardíacas , Sodio , Animales , Ratas , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Sodio/metabolismo , Masculino , Miocardio/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Ciclo del Ácido Cítrico/efectos de los fármacos , Ratas Sprague-Dawley , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/metabolismo , Intercambiador de Sodio-Calcio/metabolismo , Ubiquinona/metabolismo , Ubiquinona/análogos & derivados , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Oxidación-Reducción , Ácido Succínico/metabolismo
6.
PeerJ ; 12: e16943, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38770100

RESUMEN

The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB (Luteovulum sphaeroides EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3-4‰ resulted in an increase in the Na+ accumulation in soil, resulting in a lower rice grain yield by 12.9-22.2% in comparison with the 0‰ salinity case. Supplying the mixture of L. sphaeroides EPS18, EPS37, and EPS54 increased pH by 0.13, NH4+ by 2.30 mg NH4+ kg-1, and available P by 8.80 mg P kg-1, and decreased Na+ by 0.348 meq Na+ 100 g-1, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of L. sphaeroides EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment.


Asunto(s)
Oryza , Microbiología del Suelo , Suelo , Oryza/microbiología , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Suelo/química , Salinidad , Estrés Salino , Proteobacteria/metabolismo , Concentración de Iones de Hidrógeno , Sodio/metabolismo , Sodio/farmacología
7.
Sensors (Basel) ; 24(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38732822

RESUMEN

Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.


Asunto(s)
Imagen por Resonancia Magnética , Fantasmas de Imagen , Programas Informáticos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/instrumentación , Sodio/química , Humanos , Isótopos de Sodio , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados
8.
Methods Mol Biol ; 2799: 151-175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38727907

RESUMEN

In vertebrate central neurons, NMDA receptors are glutamate- and glycine-gated ion channels that allow the passage of Na+ and Ca2+ ions into the cell when these neurotransmitters are simultaneously present. The passage of Ca2+ is critical for initiating the cellular processes underlying various forms of synaptic plasticity. These Ca2+ ions can autoregulate the NMDA receptor signal through multiple distinct mechanisms to reduce the total flux of cations. One such mechanism is the ability of Ca2+ ions to exclude the passage of Na+ ions resulting in a reduced unitary current conductance. In contrast to the well-characterized Mg2+ block, this "channel block" mechanism is voltage-independent. In this chapter, we discuss theoretical and experimental considerations for the study of channel block by Ca2+ using single-channel patch-clamp electrophysiology. We focus on two classic methodologies to quantify the dependence of unitary channel conductance on external concentrations of Ca2+ as the basis for quantifying Ca2+ block.


Asunto(s)
Calcio , Técnicas de Placa-Clamp , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/metabolismo , Calcio/metabolismo , Técnicas de Placa-Clamp/métodos , Animales , Activación del Canal Iónico , Humanos , Sodio/metabolismo
9.
Physiol Res ; 73(2): 173-187, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38710052

RESUMEN

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.


Asunto(s)
Síndrome Cardiorrenal , Homeostasis , Sodio , Equilibrio Hidroelectrolítico , Humanos , Síndrome Cardiorrenal/metabolismo , Síndrome Cardiorrenal/fisiopatología , Animales , Homeostasis/fisiología , Equilibrio Hidroelectrolítico/fisiología , Sodio/metabolismo , Riñón/metabolismo , Riñón/fisiopatología , Desequilibrio Hidroelectrolítico/metabolismo , Desequilibrio Hidroelectrolítico/fisiopatología , Agua/metabolismo
10.
J Clin Neurosci ; 124: 115-121, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703471

RESUMEN

PURPOSE: Evidence is scarce regarding the association between hyponatremia and alterations in cognitive function among hospitalized older patients. We aimed to investigate the associations between hyponatremia and the baseline cognitive status, as well as the improvement in cognitive function, in hospitalized post-stroke patients. METHODS: This retrospective cohort study included consecutive hospitalized post-stroke patients. Serum sodium concentrations were extracted from medical records based on blood tests performed within 24 h of admission, with hyponatremia defined as a serum sodium concentration < 135 mEq/L. The main outcomes included admission and discharge scores for cognitive levels, assessed through the cognitive domain of the Functional Independence Measure (FIM-cognition), as well as the score changes observed during the hospitalization period. Multivariate linear regression analyses were used to determine the association between hyponatremia and outcomes of interest, adjusted for potential confounders. RESULTS: Data from 955 patients (mean age 73.2 years; 53.6 % men) were included in the analysis. The median baseline blood sodium level was 139 [137, 141], and 84 patients (8.8 %) exhibited hyponatremia. After full adjustment for confounders, the baseline hyponatremia was significantly and negatively associated with FIM-cognition values at admission (ß = -0.009, p = 0.016), discharge (ß = -0.038, p = 0.043), and the gain during hospital stay (ß = -0.040, p = 0.011). CONCLUSION: Baseline hyponatremia has demonstrated a correlation with decline in cognitive level over the course of rehabilitation in individuals after stroke. Assessing hyponatremia at the outset proves to be a pivotal prognostic indicator.


Asunto(s)
Disfunción Cognitiva , Hospitalización , Hiponatremia , Accidente Cerebrovascular , Humanos , Hiponatremia/etiología , Hiponatremia/sangre , Masculino , Femenino , Anciano , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/sangre , Anciano de 80 o más Años , Disfunción Cognitiva/etiología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Persona de Mediana Edad , Sodio/sangre
11.
Funct Plant Biol ; 512024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38753957

RESUMEN

Detrimental effects of salinity could be mitigated by exogenous zinc (Zn) application; however, the mechanisms underlying this amelioration are poorly understood. This study demonstrated the interaction between Zn and salinity by measuring plant biomass, photosynthetic performance, ion concentrations, ROS accumulation, antioxidant activity and electrophysiological parameters in barley (Hordeum vulgare L.). Salinity stress (200mM NaCl for 3weeks) resulted in a massive reduction in plant biomass; however, both fresh and dry weight of shoots were increased by ~30% with adequate Zn supply. Zinc supplementation also maintained K+ and Na+ homeostasis and prevented H2 O2 toxicity under salinity stress. Furthermore, exposure to 10mM H2 O2 resulted in massive K+ efflux from root epidermal cells in both the elongation and mature root zones, and pre-treating roots with Zn reduced ROS-induced K+ efflux from the roots by 3-4-fold. Similar results were observed for Ca2+ . The observed effects may be causally related to more efficient regulation of cation-permeable non-selective channels involved in the transport and sequestration of Na+ , K+ and Ca2+ in various cellular compartments and tissues. This study provides valuable insights into Zn protective functions in plants and encourages the use of Zn fertilisers in barley crops grown on salt-affected soils.


Asunto(s)
Homeostasis , Hordeum , Raíces de Plantas , Potasio , Salinidad , Zinc , Hordeum/efectos de los fármacos , Hordeum/crecimiento & desarrollo , Hordeum/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Zinc/farmacología , Zinc/metabolismo , Homeostasis/efectos de los fármacos , Potasio/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sodio/metabolismo , Estrés Salino/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo
12.
Proc Natl Acad Sci U S A ; 121(19): e2318757121, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38691591

RESUMEN

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (INaP) lies at the heart of this debate. Although INaP is widely expressed, the pacemaker hypothesis considers it essential because it endows a small subset of neurons with intrinsic bursting or "pacemaker" activity. In contrast, burstlet theory considers INaP dispensable because rhythm emerges from "preinspiratory" spiking activity driven by feed-forward network interactions. Using computational modeling, we find that small changes in spike shape can dissociate INaP from intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and preinspiratory spiking without altering the role of INaP. Our results support a unifying hypothesis where INaP and excitatory network interactions, but not intrinsic bursting or preinspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.


Asunto(s)
Potenciales de Acción , Animales , Potenciales de Acción/fisiología , Modelos Neurológicos , Neuronas/fisiología , Respiración , Red Nerviosa/fisiología , Centro Respiratorio/fisiología , Simulación por Computador , Sodio/metabolismo
13.
Eur J Cancer ; 204: 114089, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703618

RESUMEN

OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. RESULTS: We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. CONCLUSIONS: Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Sodio , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/sangre , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Masculino , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/patología , Femenino , Sodio/sangre , Anciano , Persona de Mediana Edad , Inmunoterapia/métodos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab/uso terapéutico , Biomarcadores de Tumor/sangre , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sunitinib/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/sangre , Carcinoma de Células Transicionales/secundario , Carcinoma de Células Transicionales/inmunología
14.
ACS Nano ; 18(20): 12808-12819, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38717026

RESUMEN

Considerable progress has already been made in sweat sensors based on electrochemical methods to realize real-time monitoring of biomarkers. However, realizing long-term monitoring of multiple targets at the atomic level remains extremely challenging, in terms of designing stable solid contact (SC) interfaces and fully integrating multiple modules for large-scale applications of sweat sensors. Herein, a fully integrated wristwatch was designed using mass-manufactured sensor arrays based on hierarchical multilayer-pore cross-linked N-doped porous carbon coated by reduced graphene oxide (NPCs@rGO-950) microspheres with high hydrophobicity as core SC, and highly selective monitoring simultaneously for K+, Na+, and Ca2+ ions in human sweat was achieved, exhibiting near-Nernst responses almost without forming an interfacial water layer. Combined with computed tomography, solid-solid interface potential diffusion simulation results reveal extremely low interface diffusion potential and high interface capacitance (598 µF), ensuring the excellent potential stability, reversibility, repeatability, and selectivity of sensor arrays. The developed highly integrated-multiplexed wristwatch with multiple modules, including SC, sensor array, microfluidic chip, signal transduction, signal processing, and data visualization, achieved reliable real-time monitoring for K+, Na+, and Ca2+ ion concentrations in sweat. Ingenious material design, scalable sensor fabrication, and electrical integration of multimodule wearables lay the foundation for developing reliable sweat-sensing systems for health monitoring.


Asunto(s)
Electrólitos , Grafito , Sudor , Dispositivos Electrónicos Vestibles , Sudor/química , Humanos , Grafito/química , Electrólitos/química , Iones/análisis , Calcio/análisis , Sodio/análisis , Sodio/química , Técnicas Biosensibles/instrumentación , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Potasio/análisis
15.
J Am Heart Assoc ; 13(10): e034310, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38726910

RESUMEN

BACKGROUND: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information. METHODS AND RESULTS: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS. CONCLUSIONS: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.


Asunto(s)
Hipertensión , Aprendizaje Automático , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Hipertensión/orina , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Sodio/orina , Anciano , Sodio en la Dieta/orina , Algoritmos , Valor Predictivo de las Pruebas , Autoinforme , Factores de Tiempo , Reproducibilidad de los Resultados , Estados Unidos , Urinálisis/métodos
16.
Nat Commun ; 15(1): 4218, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760331

RESUMEN

DNAzymes - synthetic enzymes made of DNA - have long attracted attention as RNA-targeting therapeutic agents. Yet, as of now, no DNAzyme-based drug has been approved, partially due to our lacking understanding of their molecular mode of action. In this work we report the solution structure of 8-17 DNAzyme bound to a Zn2+ ion solved through NMR spectroscopy. Surprisingly, it turned out to be very similar to the previously solved Pb2+-bound form (catalytic domain RMSD = 1.28 Å), despite a long-standing literature consensus that Pb2+ recruits a different DNAzyme fold than other metal ion cofactors. Our follow-up NMR investigations in the presence of other ions - Mg2+, Na+, and Pb2+ - suggest that at DNAzyme concentrations used in NMR all these ions induce a similar tertiary fold. Based on these findings, we propose a model for 8-17 DNAzyme interactions with metal ions postulating the existence of only a single catalytically-active structure, yet populated to a different extent depending on the metal ion cofactor. Our results provide structural information on the 8-17 DNAzyme in presence of non-Pb2+ cofactors, including the biologically relevant Mg2+ ion.


Asunto(s)
ADN Catalítico , Plomo , Magnesio , Zinc , ADN Catalítico/química , ADN Catalítico/metabolismo , Magnesio/metabolismo , Magnesio/química , Zinc/metabolismo , Zinc/química , Plomo/química , Plomo/metabolismo , Conformación de Ácido Nucleico , Dominio Catalítico , Modelos Moleculares , Sodio/metabolismo , Sodio/química , Metales/metabolismo , Metales/química , Espectroscopía de Resonancia Magnética , Iones
17.
BMC Nephrol ; 25(1): 152, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698368

RESUMEN

INTRODUCTION: Dysnatremia is strongly associated with poor prognosis in acute kidney injury (AKI); however, the impact of sodium trajectories on the prognosis of patients with AKI has not yet been well elucidated. This study aimed to assess the association between sodium trajectories in patients with AKI and mortality at 30-day and 1-year follow-up. METHODS: This retrospective cohort study used data from Medical Information Mart for Intensive Care (MIMIC)-IV database, and patients diagnosed with AKI within 48 h after admission were enrolled. Group-based trajectory models (GBTM) were applied to map the developmental course of the serum sodium fluctuations. Kaplan-Meier survival curve was used to compare differences in mortality in AKI patients with distinct serum sodium trajectories. Hazard ratios (HRs) were calculated to determine the association between trajectories and prognosis using Cox proportional hazard models. RESULTS: A total of 9,314 AKI patients were enrolled. Three distinct sodium trajectories were identified including: (i) stable group (ST, in which the serum sodium levels remained relatively stable, n = 4,935; 53.0%), (ii) descending group (DS, in which the serum sodium levels declined, n = 2,994; 32.15%) and (iii) ascending group (AS, in which the serum sodium levels were elevated, n = 1,383; 14.85%). There was no significant difference in age and gender distribution among the groups. The 30-day mortality rates were 7.9% in ST, 9.5% in DS and 16.6% in AS (p < 0.001). The results of 1-year mortality rates were similar (p < 0.001). In adjusted analysis, patients in the DS (HR = 1.22, 95% confidence interval [CI], 1.04-1.43, p = 0.015) and AS (HR = 1.68, 95% CI, 1.42-2.01, p = 0.013) groups had higher risks of 30-day mortality compared to those in the ST group. CONCLUSION: In patients with AKI, the serum sodium trajectories were independently associated with 30-day and 1-year mortality. Association between serum sodium level trajectories and prognosis in patients with AKI deserve further study.


Asunto(s)
Lesión Renal Aguda , Sodio , Humanos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Sodio/sangre , Persona de Mediana Edad , Anciano , Pronóstico , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier
18.
J Hypertens ; 42(6): 1086-1093, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38690907

RESUMEN

BACKGROUND: Early-life programming due to prematurity and very low birth weight (VLBW, <1500 g) is believed to contribute to development of hypertension, but the mechanisms remain unclear. Experimental data suggest that altered pressure natriuresis (increased renal perfusion pressure promoting sodium excretion) may be a contributing mechanism. We hypothesize that young adults born preterm will have a blunted pressure natriuresis response to mental stress compared with those born term. METHODS: In this prospective cohort study of 190 individuals aged 18-23 years, 156 born preterm with VLBW and 34 controls born term with birth weight at least 2500 g, we measured urine sodium/creatinine before and after a mental stress test and continuous blood pressure before and during the stress test. Participants were stratified into groups by the trajectory at which mean arterial pressure (MAP) increased following the test. The group with the lowest MAP trajectory was the reference group. We used generalized linear models to assess poststress urine sodium/creatinine relative to the change in MAP trajectory and assessed the difference between groups by preterm birth status. RESULTS: Participants' mean age was 19.8 years and 57% were women. Change in urine sodium/creatinine per unit increase in MAP when comparing middle trajectory group against the reference group was greater in those born preterm [ß 5.4%, 95% confidence interval (95% CI) -11.4 to 5.3] than those born term (ß 38.5%, 95% CI -0.04 to 92.0), interaction term P = 0.002. CONCLUSION: We observed that, as blood pressure increased following mental stress, young adults born preterm exhibited decreased sodium excretion relative to term-born individuals.


Asunto(s)
Nacimiento Prematuro , Sodio , Estrés Psicológico , Humanos , Femenino , Masculino , Adulto Joven , Estrés Psicológico/fisiopatología , Estrés Psicológico/orina , Adolescente , Sodio/orina , Estudios Prospectivos , Nacimiento Prematuro/fisiopatología , Presión Sanguínea/fisiología , Recién Nacido , Creatinina/orina , Adulto , Natriuresis
19.
Function (Oxf) ; 5(3): zqae018, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711930
20.
Medicine (Baltimore) ; 103(20): e37749, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758907

RESUMEN

There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of pneumonia. This study aimed to assess the differences in electrolyte levels between patients suffering from COVID-19 and bacterial pneumonia. This is an original, retrospective study. Two cohorts of hospitalized patients were included, 1 suffering from COVID-19 and the other from bacterial pneumonia. Their day 1 and day 3 levels of sodium, potassium, magnesium, and phosphorus, as well as their outcomes, were extracted from the charts. Statistical analysis was subsequently performed. Mean admission levels of sodium, potassium, phosphorus, and magnesium were 135.64 ±â€…6.13, 4.38 ±â€…0.69, 3.53 ±â€…0.69, and 2.03 ±â€…0.51, respectively. The mean day 3 levels of these electrolytes were 138.3 ±â€…5.06, 4.18 ±â€…0.59, 3.578 ±â€…0.59, and 2.11 ±â€…0.64, respectively. Patients suffering from bacterial pneumonia were significantly older (N = 219, mean = 64.88 ±â€…15.99) than patients with COVID-19 pneumonia (N = 240, mean = 57.63 ±â€…17.87). Bacterial pneumonia group had significantly higher serum potassium (N = 211, mean = 4.51 ±â€…0.76), and magnesium (N = 115, mean = 2.12 ±â€…0.60) levels compared to COVID-19 group (N = 227, mean = 4.254 ±â€…0.60 for potassium and N = 118, mean = 1.933 ±â€…0.38 for magnesium). Only magnesium was significantly higher among day 3 electrolytes in the bacterial pneumonia group. No significant association between electrolyte levels and outcomes was seen. We found that COVID-19 patients had lower potassium and magnesium levels on admission, possibly due to the effect of COVID-19 on the renin-angiotensin-aldosterone system as well as patient characteristics and management. We did not find enough evidence to recommend using electrolyte levels as a determinator of prognosis, but more research is needed.


Asunto(s)
COVID-19 , Hospitalización , Magnesio , Neumonía Bacteriana , Potasio , Desequilibrio Hidroelectrolítico , Humanos , COVID-19/complicaciones , COVID-19/sangre , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Hospitalización/estadística & datos numéricos , Desequilibrio Hidroelectrolítico/epidemiología , Desequilibrio Hidroelectrolítico/sangre , Neumonía Bacteriana/sangre , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/epidemiología , Potasio/sangre , Magnesio/sangre , SARS-CoV-2 , Electrólitos/sangre , Sodio/sangre , Fósforo/sangre
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