High Salt Research Articles

Concentrated, Gradient Electrolyte Design for Superior Low-Temperature Li-Metal Batteries

Improving the low-temperature performance of lithium-ion batteries is critical for their widespread adoption in cold environments. In this study, we designed a novel LHCE featuring a solvent polarity gradient, designed to maximize both room- and low-temperature ion mobility. Extremely polar fluoroethylene carbonate (FEC) and low-freezing-point, −135 °C, non-polar nonaflurobutyl methyl ether (NONA) were supplemented by two intermediate solvents with incremental step-downs in polarity. The intermediate solvents consist of methyl (2,2,2-triflooethyl) carbonate (FEMC) and either diethylene carbonate (DEC), ethyl methyl carbonate (EMC), or dibutyl carbonate (DBC). The four solvents were combined with 1 M lithium bis(fluorosulfonyl)amide (LiFSI) salt and were able to accommodate 37.5% diluent volume, resulting in ultra-low electrolyte freezing points below −120 °C. This contrasts with our previously investigated three-solvent LHCE, which only allowed for a 14% diluent volume and a −85 °C freezing point. Localized high salt concentrations were shown by less than 3% of FSI- anions being free in solution. The gradient LHCEs also showed room-temperature ionic conductivities above 10–3 S/cm and maintained high ion mobility below −40 °C. Lithium metal coin cells with LiFePO4 (LFP) cathodes featuring the gradient LHCEs, a reference three-solvent LHCE, and commercial (1 M LiPF6 in 1:1 EC:DEC) electrolyte were constructed. All gradient LHCEs outperformed both the three-solvent and commercial electrolytes at all temperatures, with the DEC-based gradient LHCE showing the best performance of 159.7 mAh/g at 25 °C and 109.2 mAh/g at −50 °C, corresponding to a 68% capacity retention. These findings highlight the potential of LHCE systems to improve battery performance in low-temperature environments and propose a new gradient design strategy for electrolytes to yield advantages of both polar and weakly polar solvents.

Strategies for genetic manipulation of the halotolerant black yeast Hortaea werneckii: ectopic DNA integration and marker-free CRISPR/Cas9 transformation.

Hortaea werneckii is a halotolerant black yeast commonly found in hypersaline environments. This yeast is also the causative agent of tinea nigra, a superficial mycosis of the palm of the hand and soles of the feet of humans. In addition to their remarkable halotolerance, this black yeast exhibits an unconventional cell division cycle, alternating between fission and budding cell division. Cell density and the salt concentration in their environment regulate which cell division cycle H. werneckii uses. Although H. werneckii have been extensively studied due to their unique physiology and cell biology, deciphering the underlying mechanisms behind these remarkable phenotypes has been limited due to the lack of genetic tools available. Here, we report a new ectopic integration protocol for H. werneckii using polyethylene glycol-CaCl2 mediated protoplast transformation. This approach relies on a drug (hygromycin B) resistance gene to select for successful integration of the genetic construct. The same construct was used to express cytosolic green fluorescent protein. Finally, we developed a marker-free CRISPR/Cas9 protocol for targeted gene deletion using the melanin synthesis pathway as a visual reporter of successful transformation. These transformation strategies will allow testing hypotheses related to H. werneckii cell biology and physiology.IMPORTANCEHortaea werneckii is a remarkable yeast capable of growing in high salt concentration, and its cell division cycle alternates between fission-like and budding. For these unique attributes, H. werneckii has gathered interest in research programs studying extremophile fungi and cell division. Most of our understanding of H. werneckii biology comes from genomic analyses, the usage of drugs to target a particular pathway, or the heterologous expression of its genes in S. cerevisiae. Nonetheless, H. werneckii has remained genetically intractable. Here, we report on two strategies to transform H. werneckii: ectopic integration of a plasmid and gene deletion using CRISPR/Cas9. These approaches will be fundamental to expanding the experimental techniques available to study H. werneckii, including live-cell imaging of cellular processes and reverse genetic approaches.

Coulombic Condensation of Liquefied Gas Electrolytes for Li Metal Batteries at Ambient Pressure

The concept of employing highly concentrated electrolytes has been widely incorporated into electrolyte design, due to their enhanced Li‐metal passivation and oxidative stability compared to their diluted counterparts. However, issues such as high viscosity and sub‐optimal wettability, compromise their suitability for commercialization. In this study, we present a highly concentrated dimethyl ether‐based electrolyte that appears as a liquid phase at ambient conditions via Li+ ‐ solvents ion‐dipole interactions (Coulombic condensation). Unlike conventional high salt concentration ether‐based electrolytes, it demonstrates enhanced transport properties and fluidity. The anion‐rich solvation structure also contributes to the formation of a LiF‐rich salt‐derived solid electrolyte interphase, facilitating stable Li metal cycling for over 1000 cycles at 0.5 mA cm‐2, 1 mAh cm‐2 condition. When combined with a sulfurized polyacrylonitrile (SPAN) electrode, the electrolyte effectively reduces the polysulfide shuttling effect and ensures stable performance across a range of charging currents, up to 6 mA cm‐2. This research underscores a promising strategy for developing an anion‐rich, high concentration ether electrolyte with decreased viscosity, which supports a Li metal anode with exceptional temperature durability and rapid charging capabilities.

Coulombic Condensation of Liquefied Gas Electrolytes for Li Metal Batteries at Ambient Pressure.

The concept of employing highly concentrated electrolytes has been widely incorporated into electrolyte design, due to their enhanced Li-metal passivation and oxidative stability compared to their diluted counterparts. However, issues such as high viscosity and sub-optimal wettability, compromise their suitability for commercialization. In this study, we present a highly concentrated dimethyl ether-based electrolyte that appears as a liquid phase at ambient conditions via Li+ - solvents ion-dipole interactions (Coulombic condensation). Unlike conventional high salt concentration ether-based electrolytes, it demonstrates enhanced transport properties and fluidity. The anion-rich solvation structure also contributes to the formation of a LiF-rich salt-derived solid electrolyte interphase, facilitating stable Li metal cycling for over 1000 cycles at 0.5 mA cm-2, 1 mAh cm-2 condition. When combined with a sulfurized polyacrylonitrile (SPAN) electrode, the electrolyte effectively reduces the polysulfide shuttling effect and ensures stable performance across a range of charging currents, up to 6 mA cm-2. This research underscores a promising strategy for developing an anion-rich, high concentration ether electrolyte with decreased viscosity, which supports a Li metal anode with exceptional temperature durability and rapid charging capabilities.

Integrated transcriptomic and metabolomic analyses uncover the key pathways of Limonium bicolor in response to salt stress.

Salinity significantly inhibits plant growth and development. While the recretohalophyte Limonium bicolor can reduce its ion content by secreting salt, the metabolic pathways it employs to adapt to high salt stress remain unclear. This study aims to unravel this enigma through integrated transcriptomic and metabolomic analyses of L. bicolor under salt stress conditions. The results showed that compared to the control (S0), low salt treatment (S1) led to a significant increase in plant growth, photosynthesis efficiency and antioxidant enzyme activity but caused no significant changes in organic soluble substance and ROS contents. However, high salt treatments (S3 and S4) led to a significant decrease in plant growth, photosynthesis efficiency and antioxidant enzyme activity, accompanied by a significant increase in organic soluble substance and ROS contents. A significant increase in phenolic compounds, such as caffeoyl shikimic acid and coniferin, upon the treatments of S1, S3 and S4, and a decrease and increase in flavonoids upon the treatments of S1 and S3 were also observed, respectively. This study also demonstrated that the expression patterns of key genes responsible for the biosynthesis of these metabolites are consistent with the observed trends in their accumulation levels. These results suggest that under low salt stress conditions, the halophyte L. bicolor experiences minimal osmotic and oxidative stress. However, under high salt stress conditions, it suffers severe osmotic and oxidative stress, and the increase in organic soluble substances and flavonoids serves as a key response to these stresses and also represents a good strategy for the alleviation of them.

Modification of blend reverse osmosis membranes using ZrO2 for desalination process purposes

Desalination of water is a crucial step in the process of obtaining potable water. One of the main challenges for the researchers is its efficient application and affordable preparation. It was planned to prepare the flat sheet membranes using cellulose acetate as a base polymer, and polyvinyl alcohol (PVA) as an additive with dosing of (0.1, 0.3, 0.5, and 0.7 wt%) from zirconium oxide (ZrO2) nanoparticle. SEM, TEM, and XRD analyses were used to characterize the generated ZrO2 nanoparticle in order to confirm its nano-size and crystal structure. The surface morphologies and existence of the dense layer, which is the typical property of the RO membrane capable of salt separation, were identified on the manufactured RO membranes by SEM. Membranes prepared by embedding 0.5 wt%ZrO2 with PVA/CA proved efficient as RO membranes using 2000 ppm NaCl and exhibited high salt rejection of 97% and water permeability of 12.5 LMH. Also, there is a decrease in the NaCl removal tendency was observed with the excessive dosages of ZrO2 with 0.7 wt%, which was due to the concentration polarization, which blocks the pores on the surfaces of the membranes. The antifouling behavior of the prepared membranes was tested using bovine serum albumin (BSA), the results indicate the low irreversible resistance, total fouling resistance, and high flux recovery ratio compared to the neat membrane. The prepared membranes have a stable salt rejection and water productivity even after demonstrating with chlorine (25–100 mg l−1 of NaOCl for 120 min).

Biodegradation of various edible oils and fat by Staphylococcus petrasii sub sp. jettensis VSJK R1 for application in bioremediation of lipid rich restaurant wastewater.

The disposal of fat, oil, and grease (FOG) pollutants from various sources, including restaurants, food processing facilities, and domestic kitchens, poses significant challenges to wastewater treatment systems. In this study, we isolated and characterized a novel bacterial strain. The result of 16S rRNA gene and phylogenetic analysis showed that the isolate was Staphylococcus petrasii sub sp. jettensis and named as VSJK R1 (Fig. S1). It was tested for its biodegradation potential of FOG contaminants. Our investigation revealed that Staphylococcus petrasii sub sp. jettensis VSJK R1 effectively degraded a variety of edible oils, including soybean, sunflower, cottonseed, palm, groundnut, and butter, with notable efficiency. Optimization studies were conducted to determine the optimal conditions for biodegradation, including the effects of nitrogen, carbon, phosphorus, pH, temperature, and salt concentration. Results indicated that organic nitrogen sources and glucose as carbon source significantly enhanced biodegradation rates, while the addition of phosphorus further improved degradation efficiency within specific concentration ranges. Moreover, the optimal pH for biodegradation was found to be neutral, with temperature ranging between 22°C and 45°C favoring microbial activity. Remarkably, Staphylococcus petrasii sub sp. jettensis VSJK R1 exhibited resilience to high salt concentrations, making it suitable for treatment of wastewater with elevated salt content. Additionally, comparative studies with other microbial strains underscored the unique biodegradation capabilities of Staphylococcus petrasii sub sp. jettensis VSJK R1, particularly in degrading various edible oils. The results suggest promising applications of this novel isolate in bioremediation efforts targeting FOG pollutants in wastewater treatment plants and grease traps. Future research may focus on scaling up the bioremediation process and field testing the efficacy of Staphylococcus petrasii sub sp. jettensis VSJK R1 in real-world wastewater treatment scenarios.

Fast Seawater Desalination Integrated with Electrochemical CO2 Reduction.

Coupling desalination with electrocatalytic reactions is an emerging approach to simultaneously addressing freshwater scarcity and greenhouse gas emissions. However, the salt removal rate in such processes is slow, and the applicable water sources are often limited to those with high salt concentrations. Herein, we show high-performance electrocatalytic desalination by coupling with electrochemical CO2 reduction using a carbon catalyst. A ZIF-8-derived carbon catalyst embedded with Cu nanoparticles delivers a high Faradaic efficiency of 94.3% for CO production at 288 μmol cm-2 h-1. The efficient CO2 electroreduction generates high current densities, which drive fast salt ion transfer across ion exchange membranes. The integrated device enables one of the quickest salt removal rates of 1043.49 μg cm-2 min-1 among various desalination methods. Drinking water can be obtained with an ion removal rate of 99% when natural seawater is used as the water source.

Fast Seawater Desalination Integrated with Electrochemical CO2 Reduction

Coupling desalination with electrocatalytic reactions is an emerging approach to simultaneously addressing freshwater scarcity and greenhouse gas emissions. However, the salt removal rate in such processes is slow, and the applicable water sources are often limited to those with high salt concentrations. Herein, we show high‐performance electrocatalytic desalination by coupling with electrochemical CO2 reduction using a carbon catalyst. A ZIF‐8‐derived carbon catalyst embedded with Cu nanoparticles delivers a high Faradaic efficiency of 94.3% for CO production at 288 μmol cm‐2 h‐1. The efficient CO2 electroreduction generates high current densities, which drive fast salt ion transfer across ion exchange membranes. The integrated device enables one of the quickest salt removal rates of 1043.49 μg cm‐2 min‐1 among various desalination methods. Drinking water can be obtained with an ion removal rate of 99% when natural seawater is used as the water source.

Distillers’ grains carbon for high-performance capacitive deionization

Because of its abundant supply and long-term availability, biomass-based activated carbon is one of the first porous carbon electrode materials recommended for capacitive deionization. This work describes the preparation of biomass distillers’ grains-based porous carbon materials with high capacity and quick desalination rates by a sequence of thermal carbonization, chemical activation, and de-ashing from waste distillers’ grains of Shanxi Fenjiu Liquor. Compared to other carbon materials, the optimum material had a high salt adsorption capacity of 41.85 mg∙g−1 at 1.2 V with a starting concentration of 500 ppm NaCl. Following acidification during the ash removal process, the material’s surface became rich in oxygen-containing functional groups such as carboxyl, as well as a huge number of active sites exposed by the ultra-high specific surface area and profound pore structures. The material had a substantially higher average salt adsorption rate of 17.67 mg∙g−1∙min−1, compared with other carbon materials. After cycles, it maintained 75 % of its maximum capacity in cycle 25. These positive results highlight the potential of biomass distillers’ grains-based carbon materials in desalination. This work introduces new ways to treating waste distillers’ grains from the Fenjiu liquor production process.

The effect of combined aqueous extract of Turmeric and curry leaves on Haematological parameters and histology of the lungs in high salt fed Wistar rat.

The effect of combined aqueous extract of Turmeric and curry leaves on Haematological parameters and histology of the lungs in high salt fed Wistar rat.

Impact of combined aqueous extracts of Turmeric and Curry leaf on the reproductive parameters of high salt fed male Wistar rats

Impact of combined aqueous extracts of Turmeric and Curry leaf on the reproductive parameters of high salt fed male Wistar rats

Collagen peptide and taurine synergistically improve hypertensive kidney injury induced by high salt diet through gut-kidney axis

Hypertensive kidney injury is significantly associated with oxidative stress, inflammation and gut microbiota. Collagen peptide and taurine (Tau) are key natural compounds known for their antioxidant, anti-inflammatory, and intestinal flora improvement. However, the potential synergistic actions of combining collagen peptides with Tau on hypertensive kidney damage remain unclear. Therefore, our study investigated the effects of collagen peptide LALFVPR (LR-7) derived from Harpadon nehereus in conjunction with Tau on renal injury in high salt (HS)-induced hypertension. The results showed that combination of LR-7 and Tau significantly alleviated renal fibrosis, glomerular atrophy, and impaired renal function in hypertensive mice. Furthermore, this combination outperformed individual treatments with either LR-7 or Tau alone in enhancing antioxidant enzyme activity while decreasing inflammatory factors and adhesion molecules levels in the kidneys. Moreover, LR-7 and Tau synergistically ameliorated HS-induced intestinal flora disturbance by promoting microbial diversity and adjusting the ratio of beneficial and harmful bacteria. Our research is pioneering in demonstrating that LR-7 combined with Tau may exert a synergistic effect on mitigating kidney damage in HS-induced hypertension through the gut-renal axis. This investigation provides a new strategy for utilizing combinations of food-derived functional compounds to effectively address complications arising from hypertension.

Stimulated Pickering emulsion stabilized by binary particles with contrasting wettability and trace surfactant

The investigationof self-assembled particle structures at fluid interfaces has gained considerable interest across various fields. In particular, Pickering emulsions (PEs) stabilized by binary particles co-assembling at these interfaces have attracted even more attention. To explore the self-assembly process of superhydrophobic and superhydrophilic particles at oil–water (O/W) interfaces influenced by a trace amount of surfactant, a series of experiments were conducted. A small quantity (0.01 mmol·L−1) of dodecyltrimethylammonium bromide (DTAB) was introduced, establishing a variable stable emulsion system with high salt tolerance, capable of withstanding up to 6 mol·L−1 NaCl, in synergism with the particles. The DTAB concentration required to stabilize the O/W emulsion with particles was as low as 0.001 mmol·L−1. The stability and type of the resulting emulsion could be adjusted by varying the ratio of hydrophobic to hydrophilic particle (R) or by modifying acid/base conditions. The systems exhibited robust cyclic acid/base regulated demulsification and phase inversion behavior, maintaining stability over at least 10 cycles. Results indicated that the stability and nature of the emulsion were influenced by the curvature of the interface formed by the self-assembled interfacial particle structures, arising from the competitive adsorption of both types of particles and trace surfactant. Further analysis revealed a correlation between interfacial curvature and the surface charges of the particles, which could be modulated through DTAB adsorption. This study elucidated the behavior of hydrophilic and hydrophobic particle self-assembly at interfaces, provided a straightforward strategy for co-preparing switchable emulsions using superhydrophilic and superhydrophobic particles, and expanded the range of amphiphilic particles available for producing PEs. This approach presents significant potential for future research and applications in the field of PEs.

Differential germination responses of plump and shriveled seeds to environmental factors and storage conditions in Tamarix laxa Willd.

Tamarix laxa Willd. is a vital shrub widely distributed in arid and semi-arid regions. It serves as an excellent species for sand-fixing afforestation in saline-alkali and sandy desert lands and has medicinal properties for wind-dispelling and detoxifying. This plant produces two types of seeds: plump and shriveled. However, the effect of seed plumpness on germination has not been extensively studied. In this research, we found that 42% of the seeds in T. laxa were plump, and 58% were shriveled. We then investigated how different temperatures, light conditions, salt concentrations, and storage methods affect the germination of these seeds. Shriveled seeds were significantly smaller and had a lower germination percentage compared to plump seeds. T. laxa seeds exhibited a broad adaptability to temperature. Plump seeds showed over 90% germination at three different temperatures, whereas shriveled seeds had a 57% germination percentage at 15/30oC. Continuous darkness significantly reduced the germination percentage for both seed types. Although T. laxa seeds displayed some salt tolerance, high salt concentrations (0.6mol/L NaCl) markedly decreased their germination percentage. Freshly mature seeds initially had a 99% germination percentage. However, seeds stored at room temperature for 90 days nearly lost their viability. In contrast, seeds stored at -18 oC for 180 days maintained a germination percentage above 80%. Low-temperature storage effectively delayed the short-term loss of seed vitality. This study offers comprehensive insights into T. laxa seed germination, providing valuable information for desert restoration efforts.

Mitochondrial dysfunction of Astrocyte induces cell activation under high salt condition

Mitochondrial dysfunction of Astrocyte induces cell activation under high salt condition

Mixed-mode separation of antisense oligonucleotides using a single column with complementary anion-exchange and hydrophobic interaction chromatography approaches

The current study investigates the use of mixed-mode chromatography as a combination of anion-exchange (AEX) and hydrophobic interaction chromatography (HIC) for the analysis and purification of single-stranded antisense oligonucleotides with stereo-controlled phosphorothioate inter- nucleotide linkages.Initially a Scherzo-SS-C18 trimodal stationary phase with reversed-phase/AEX/ cation-exchange (CEX) functionalities is systematically evaluated to reveal the presence of U-shaped retention composed of two retention modes namely AEX and HIC, where the latter was also observed on related trimodal Scherzo SM and SW analogues. For the first time, retention and separation of deprotected oligonucleotides was described on a single mixed-mode column using a combination of AEX and HIC. This methodology was later applied to an alternative reversed-phase/AEX support, Newcrom BH, displaying similar retention trends under dual salt / organic modifier gradients. The merit of the method was assessed on the basis of separations between a phosphodiester (PO) impurity and phosphorothioate (PS) target for an assortment of selected 2’-O-methoxyethyl 18- to 20-mer single-stranded antisense oligonucleotides. Various parameters were evaluated mostly under HIC conditions including organic modifier percentage, type of salt, temperature, pH and type of buffer in the mobile phase. Retention of the oligonucleotides was significantly affected by the acetonitrile composition and the type of salt ((NH4)2SO4, NaBr, NaCl) where the latter NaCl also afforded resolution between the PS target and closely eluting PO impurities. Small changes in pH between 6.5 and 7 using MES and TRIS respectively demonstrated notable differences in retention and resolution. The optimized methods were compared against a range of traditional supports and applied to various mixed-mode analogues, possessing embedded amino acid, complex forming weak cation-exchange and terminal strong cation-exchange functionalities. The mixed-mode supports displayed HIC retention and better resolution between PS target and PO impurity was evident with a more focused 5% acetonitrile gradient over its 10% counterpart. Overall, throughout the study AEX and HIC demonstrated comparable resolution trends.Finally, the optimized HIC method was applied to a selected 18-mer antisense oligonucleotide at semi-preparative scale using the Newcrom BH column, affording purities of 60-80% and recoveries of 52-76%. Although HIC does not provide better separations between PS and PO than AEX, it opens possibilities to operate under non-denaturing conditions and allows purification of samples containing high salt content, as a standalone method or post AEX without a prior desalting step, which can result in 20-30% sample loss.

Preparation and properties of a new type of temperature-resistant and salt-resistant fluid loss additive ADIM for oil well cement

In order to adapt to the deep high temperature and high salt cementing operation environment, itaconic acid (IA), N,N-dimethylacrylamide (DMAA), 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and heterocyclic alkenes (R) were used as polymerization monomers in this paper. A temperature-resistant and salt-resistant fluid loss additive named ADIM was successfully prepared by free radical aqueous solution polymerization and orthogonal experiment. Thermogravimetric, infrared, nuclear magnetic resonance, and elemental analysis have been utilized for assessing the copolymers' structure and heat resistance. The results showed that the target copolymers with thermal decomposition temperature up to 300 ℃ were successfully prepared. A methodical evaluation was conducted on ADIM's application performance. The results show that when the ADIM content is 5 %, the water loss of fresh water cement slurry is only 44 mL at 220 ℃, and the water loss of saturated brine cement slurry is only 64 mL at 180 ℃.In addition to the excellent temperature resistance and salt resistance, the overall performance of ADIM is also good. The mechanism of ADIM was studied by mercury intrusion experiment, scanning electron microscope and TOC test. The results show that ADIM can be adsorbed on the cement particles, effectively reducing the porosity and pore size of the filter cake, thereby reducing the water loss of the cement slurry. ADIM has excellent temperature and salt resistance, which is of great significance for guiding the development of deep oil and gas resources.

Angiotensin II Exposure In Vitro Reduces High Salt-Induced Reactive Oxygen Species Production and Modulates Cell Adhesion Molecules’ Expression in Human Aortic Endothelial Cell Line

Background/Objectives: Increased sodium chloride (NaCl) intake led to leukocyte activation and impaired vasodilatation via increased oxidative stress in human/animal models. Interestingly, subpressor doses of angiotensin II (AngII) restored endothelium-dependent vascular reactivity, which was impaired in a high-salt (HS) diet in animal models. Therefore, the present study aimed to assess the effects of AngII exposure following high salt (HS) loading on endothelial cells’ (ECs’) viability, activation, and reactive oxygen species (ROS) production. Methods: The fifth passage of human aortic endothelial cells (HAECs) was cultured for 24, 48, and 72 h with NaCl, namely, the control (270 mOsmol/kg), HS320 (320 mOsmol/kg), and HS350 (350 mOsmol/kg). AngII was administered at the half-time of the NaCl incubation (10−4–10−7 mol/L). Results: The cell viability was significantly reduced after 24 h in the HS350 group and in all groups after longer incubation. AngII partly preserved the viability in the HAECs with shorter exposure and lower concentrations of NaCl. Intracellular hydrogen peroxide (H2O2) and peroxynitrite (ONOO−) significantly increased in the HS320 group following AngII exposure compared to the control, while it decreased in the HS350 group compared to the HS control. A significant decrease in superoxide anion (O2.−) formation was observed following AngII exposure at 10−5, 10−6, and 10−7 mol/L for both HS groups. There was a significant decrease in intracellular adhesion molecule 1 (ICAM-1) and endoglin expression in both groups following treatment with 10−4 and 10−5 mol/L of AngII. Conclusions: The results demonstrated that AngII significantly reduced ROS production at HS350 concentrations and modulated the viability, proliferation, and activation states in ECs.

Establishment of a HFpEF model using female Dahl salt-sensitive rats: a valuable tool for elucidating the pathophysiology of HFpEF in women.

The pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains unclear, and effective treatments are limited. HFpEF is more prevalent in females, indicating potential gender differences in its pathogenesis. However, no female HFpEF model animals have been established. Hypertension is a major contributor to HFpEF, and sympathetic activation is thought to play a role in both conditions. This study aimed to establish a female HFpEF model using hypertensive Dahl salt-sensitive rats and to assess the presence of sympathetic activation. Seven-week-old female Dahl salt-sensitive rats were fed an 8% high-salt diet (HS group, n = 6), while a low-salt diet group (LS group, n = 9) served as controls. The HS group exhibited increased systolic blood pressure and heart rate. Echocardiography revealed an increased left ventricular (LV) wall thickness, a decreased E/A ratio, and an increased E/e' ratio, all indicative of diastolic dysfunction without reduced LV ejection fraction. Additionally, the HS group showed elevated LV end-diastolic pressure, LV weight, and lung weight, along with histological cardiomyocyte hypertrophy and interstitial fibrosis. Gene expression markers for cardiac hypertrophy and fibrosis were also increased. Renal function was significantly impaired, and plasma norepinephrine levels were elevated, consistent with heightened pre-sympathetic neuronal activity in the brain. In conclusion, high salt loading from 7 weeks of age in female Dahl salt-sensitive rats induced hypertensive HFpEF phenotypes with LV hypertrophy and fibrosis, and sympathetic activation by 16 to 19 weeks of age. This model provides a valuable tool for studying HFpEF pathophysiology in women.