SCN1A intronic variants impact on Nav1.1 protein expression and sodium channel function, and associated with epilepsy phenotypic severity.

High-throughput sequencing has identified numerous intronic variants in the SCN1A gene in epilepsy patients. Abnormal mRNA splicing caused by these variants can lead to significant phenotypic differences, but the mechanisms of epileptogenicity and phenotypic differences remain unknown. Two variants, c.4853-1 G>C and c.4853-25 T>A, were identified in intron 25 of SCN1A, which were associated with severe Dravet syndrome (DS) and mild focal epilepsy with febrile seizures plus (FEFS+), respectively. The impact of these variants on protein expression, electrophysiological properties of sodium channels and their correlation with epilepsy severity was investigated through plasmid construction and transfection based on the aberrant spliced mRNA. We found that the expression of truncated mutant proteins was significantly reduced on the cell membrane, and retained in the cytoplasmic endoplasmic reticulum. The mutants caused a decrease in current density, voltage sensitivity, and an increased vulnerability of channel, leading to a partial impairment of sodium channel function. Notably, the expression of DS-related mutant protein on the cell membrane was higher compared to that of FEFS+-related mutant, whereas the sodium channel function impairment caused by DS-related mutant was comparatively milder than that caused by FEFS+-related mutant. Our study suggests that differences in protein expression levels and altered electrophysiological properties of sodium channels play important roles in the manifestation of diverse epileptic phenotypes. The presence of intronic splice site variants may result in severe phenotypes due to the dominant-negative effects, whereas non-canonical splice site variants leading to haploinsufficiency could potentially cause milder phenotypes.

Can cadmium-contaminated rice be used to produce food additive sodium erythorbate?

Cadmium (Cd) in rice is a significant concern for its quality and safety. Currently, there is a crucial need to develop cost-effective and efficient ways to remove Cd or re-utilize Cd-contaminated rice. The food additive sodium erythorbate is produced via 2-ketogluconic acid (2KGA) fermentation by Pseudomonas plecoglossicida and lactonization using starch-rich raw materials, such as rice. We aimed to determine whether cadmium-contaminated rice can be used to produce sodium erythorbate. To achieve this aim, the migration of cadmium during the production of sodium erythorbate from Cd-contaminated rice was studied. Five rice varieties with different Cd contents from 0.10 to 0.68 mg/kg were used as raw materials. The results indicated the presence of Cd in rice and CaCO3 did not have a notable impact on the fermentation performance of 2KGA. The acidification of 2KGA fermentation broth, the addition of K4Fe(CN)6·3H2O and ZnSO4, and 2KGA purification using cation exchange effectively removed >98% of the Cd in the fermentation broth, but the 2KGA yield remained high at approximately 94%. The sodium erythorbate synthesized from Cd-contaminated rice was of high quality and free from Cd, meeting the requirements of the Chinese National Standard, GB 1886.28-2016. The study provided a safe and effective strategy for comprehensively utilizing Cd-contaminated rice to produce high value-added food additive.

Effect of concentration and wavelength of excitation on the photophysics of salicylate anion in acetonitrile and water.

Sodium salicylate (NaSA) molecule exists as salicylate anion in acetonitrile (ACN) and water solvents, and exhibits large Stokes shifted fluorescence due to excited state intramolecular proton transfer (ESIPT), with decay times of âˆ¼5 ns in ACN and âˆ¼3.9 ns in water by 300 nm (absorption maxima) excitation. Previous studies report both ground and excited state enol-keto tautomerization in ACN, but only excited state tautomerization in water at 10-4 M. However, the current work explores the effect of concentration and excitation wavelengths on the photoinduced dynamics of ESIPT in the salicylate anion. On increasing the concentration of NaSA, no change in absorption spectra appears in both the solvents, and emission spectra of NaSA in water remain unaffected by changes in concentration or excitation wavelength, whereas, a slight red shift and decrease in FWHM appears in ACN. Time-domain fluorescence measurements show predominantly single-exponential decay throughout the emission profile by 300 nm excitation above the 10-5 M concentration in both the solvents, while by 375 nm excitation, multi-exponential fluorescence decay is observed at low concentrations, and as the concentration of NaSA increases, this decay behaviour tends to converge towards a single exponential decay. These results suggest that solute-solvent interactions stabilize the ground-state intermolecular hydrogen-bonded species at low concentrations, while higher concentrations weaken these interactions, leading to emission solely from the salicylate anion. Peak fit analysis of excitation spectra confirms enol-keto tautomerization in both the solvents, with the keto form being more stabilized in ACN. These findings underscore that in ACN, behaviour of NaSA is influenced by both concentration and excitation wavelength and contrary to previous reports, the keto form of the molecule is also present in water, though at a very low concentration and an increase in non-radiative transitions in water cause fluorescence quenching.

Fluorescent probes based on N-CQDs: For direct detection of food additives STPP and Al3.

Sodium tripolyphosphate (STPP), as one of the many food additives, can cause gastrointestinal discomfort and a variety of adverse reactions when ingested by the human body, which is a great potential threat to human health. Therefore, it is necessary to develop a fast, sensitive and simple method to detect STPP in food. In this study, we synthesized a kind of nitrogen-doped carbon quantum dots (N-CQDs), and were surprised to find that the addition of STPP led to the gradual enhancement of the emission peaks of the N-CQDs, with a good linearity in the range of 0.067-1.96 µM and a low detection limit as low as 0.024 µM. Up to now, there is no report on the use of carbon quantum dots for the direct detection of STPP. Meanwhile, we found that the addition of Al3+ effectively bursts the fluorescence intensity of N-CQDs@STPP solution and has a good linear relationship in the range of 0.33-6.25 µM with a lower detection limit of 0.24 µM. To this end, we developed a fluorescent probe to detect STPP and Al3+. In addition, the probe was successfully applied to the detection of bread samples, which has great potential for practical application.

Sodium salicylate as a green fluorescent probe for ultrasensitive determination of vonoprazan fumarate via fluorescence switch off strategy; greenness assessment.

A green, simple and sensitive spectrofluorometric approach for determining vonoprazan fumarate in bulk and pharmaceutical dosage form by turning off the fluorescence of sodium salicylate is developed. The addition of vonoprazan fumarate reduced linearly the fluorescence intensity of 0.4 mM sodium salicylate at λem 408 nm and at λex 330 nm. The approach was found to be linear in the 50.0-3000.0 ng/mL range. The limits of detection and quantification were 10.97 and 33.23 ng/mL, respectively. The presented method proved its suitability in determination of vonoprazan fumarate in its pure and pharmaceutical dosage form. This method employs water as the exclusive solvent and utilizes safe reagents, evaluated using the Analytical Eco Scale, Green Analytical Procedure Index (GAPI), and carbon footprint. In contrast, previous methods relied on toxic reagents and required extended heating times, resulting in higher environmental impact. The novel method not only enhances analytical efficiency but also aligns with green chemistry principles, offering a sustainable solution for routine pharmaceutical analysis.

A pH switchable hydrophilic fluorescent BODIPY sodium disulfonate for Fe3+ multicolor detection: Experimental and DFT studies.

BODIPY-based chemosensors are widely used owing to merits like good selectivity, high fluorescence quantum yield, and excellent optical stability. As such, a pH-switchable hydrophilic fluorescent probe, BODIPY-PY-(SO3Na)2, was developed for detection of Fe3+ ion in aqueous solutions. BODIPY-PY-(SO3Na)2 revealed strong fluorescence intensity and was responsive to pH value in the range of 6.59-1.96. Additionally, BODIPY-PY-(SO3Na)2 showed good selectivity and sensitivity towards Fe3+. A good linear relationship for Fe3+ detection was obtained from 0.0 µM to 50.0 µM with low detecting limit of 6.34 nM at pH 6.59 and 2.36 nM at pH 4.32, respectively. The response to pH and detection of Fe3+ induced obvious multicolor changes. BODIPY-PY-(SO3Na)2 can also be utilized to quantitatively detect Fe3+ in real water sample. Different mechanisms of Fe3+ detection at investigated pH values were unraveled through relativistic density functional theory (DFT) calculations in BODIPY-PY-(SO3Na)2 and experiments of coexisting cations, anions and molecules. These results enabled us to gain a deeper understanding of the interactions between BODIPY-PY-(SO3Na)2 and Fe3+ and provide valuable fundamental information for design of efficient multicolor chemosensors for Fe3+ as well.

Coal-derived boron and phosphorus co-doped activated carbon with expanded interlayer space for high performance sodium ion capacitor anode.

Aiming at the key problem of Na+ insertion difficulty and low charge transfer efficiency of activated carbon materials. It is an effective strategy to increase the lattice spacing and defect concentration by doping to reduce the ion diffusion resistance and improve the kinetics. Hence, anthracitic coal is used to prepare activated carbon (AC) and B,P-doped activated carbon (B,P-AC) as the cathode and anode materials for high-performance all-carbon SICs, respectively. AC cathode material has high specific surface area and reasonable micropore structure, which shows excellent capacitance performance. B,P-AC anode material has the advantages of extremely high specific surface area (1856.1 m2/g), expanded interlayer spacing (0.40 nm) and uniform distribution of B and P heteroatoms. Hence, B,P-AC anode achieves a highly reversible Na+ storage capacity of 243 mAh/g at a current density of 0.05 A/g. Density functional theory (DFT) calculations further verify that B,P-AC has stronger Na+ storage performance. The final assembled B,P-AC//AC SIC offers a high energy density of 109.78 Wh kg-1 and a high-power density of 10.03 kW kg-1. The high-performance coal-derived activated carbon of this work provides a variety of options for industrial production of electrode materials for sodium ion capacitors.

Synergetic interface engineering and space-confined effect in CoSe2@Ti3C2Tx heterostructure for high power and long life sodium ion capacitors.

The intriguing characteristics of two-dimensional (2D) heterostructures stem from their unique interfaces, which can improve ion storage capability and rate performance. However, there are still challenges in increasing the proportion of heterogeneous interfaces in materials and understanding the complex interaction mechanisms at these interfaces. Here, we have successfully synthesized confined CoSe2 within the interlayer space of Ti3C2Tx through a simple solvothermal method, resulting in the formation of a superlattice-like heterostructures of CoSe2@Ti3C2Tx. Both density functional theory (DFT) calculations and experimental results show that compared with CoSe2 and Ti3C2Tx, CoSe2@Ti3C2Tx can significantly improve adsorption of Na+ ions, while maintaining low volume expansion and high Na+ ions migration rate. The heterostructure formed by MXene and CoSe2 is a Schottky heterostructure, and its interfacial charge transfer induces a built-in electric field that promotes rapid ion transport. When CoSe2@Ti3C2Tx was used as an anode material, it exhibits a high specific capacity of up to 600.1 mAh/g and an excellent rate performance of 206.3 mAh/g at 20 A/g. By utilizing CoSe2@Ti3C2Tx as the anode and activated carbon (AC) as the cathode, the sodium-ion capacitor of CoSe2@Ti3C2Tx//AC exhibits excellent energy and power density (125.0 Wh kg-1 and 22.5 kW kg-1 at 300.0 W kg-1 and 37.5 Wh kg-1, respectively), as well as a long service life (86.3 % capacity retention over 15,300 cycles at 5 A/g), demonstrating its potential for practical applications.

High-throughput arousing interconnected interfaces for excellent sodium storage chemistry.

Heterostructures endow electrochemical hybrids with promising energy storage properties owing to synergistic effects and interfacial interaction. However, developing a facile but effective approach to maximize interface effects is crucial but challenging. Herein, a bimetallic sulfide/carbon heterostructure is realized in a confined carbon network via a high-throughput template-assisted strategy to induce highly active and stable electrode architecture. The designed heterostructures not only yield abundant interconnected Co9S8/MoS2/N-doped carbon (Co9S8/MoS2/NC) heterojunctions with continuous channels for ion/electron transfer but maintain excellent conversion reversibility. Serving as anode for sodium storage, the Co9S8/MoS2/NC framework displayed excellent sodium storage properties (reversible capacity of 480 mAh/g after 100 cycles at 0.2 A/g and 286.2 mAh/g after 500 cycles at 2 A/g). Given this, this study can guide future design protocols for interface engineering by forming dynamic channels of conversion reaction kinetics for potential applications in high-performance electrodes.

Saloplastics based on protein-peptides complexes immobilizing organic molecules in gastrointestinal drug delivery for ulcerative colitis treatment.

Ulcerative colitis (UC) stands as a chronic inflammatory intestinal disease. This study aimed to explore a sustained-release strategy to alleviate DSS-induced colitis in mice using polyelectrolyte complexes (PECs) encapsulating an alkaloid, isoliensinine (ISO). The drug delivery platform, termed "Saloplastics (SAL)", was prepared by fabrication of PECs through the solid-liquid phase separation of sodium caseinate (SC) and ε-polylysine (EPL), followed by centrifugation to yield compact structures. Coarse-grained molecular dynamics simulations demonstrated that SAL had a nanorod-like structure formation between EPL and SC, which implied that the self-assembly of SAL is driven by hydrophobic aggregation and strong electrostatic attractions. A comprehensive evaluation of SAL was conducted, including characterizations of its physicochemical and biological properties. The results showed SAL had thermal plasticization properties and excellent swelling capacity as well as susceptibility to hydrolysis by pH and proteinase in simulated gastric fluid. Moreover, SAL displayed a porous morphology with high surface area for immobilizing organic molecules. ISO@SAL, formulated by ISO encapsulated in SAL, not only demonstrated high potency in alleviating DSS-induced colitis in mice, but also increased the dosing intervals from one day to three days. In conclusion, SAL is a biocompatible sustained-release oral drug delivery platform for gastrointestinal applications.

Optimization Strategies of Na3V2(PO4)3 Cathode Materials for Sodium-Ion Batteries.

Na3V2(PO4)3 (NVP) has garnered great attentions as a prospective cathode material for sodium-ion batteries (SIBs) by virtue of its decent theoretical capacity, superior ion conductivity and high structural stability. However, the inherently poor electronic conductivity and sluggish sodium-ion diffusion kinetics of NVP material give rise to inferior rate performance and unsatisfactory energy density, which strictly confine its further application in SIBs. Thus, it is of significance to boost the sodium storage performance of NVP cathode material. Up to now, many methods have been developed to optimize the electrochemical performance of NVP cathode material. In this review, the latest advances in optimization strategies for improving the electrochemical performance of NVP cathode material are well summarized and discussed, including carbon coating or modification, foreign-ion doping or substitution and nanostructure and morphology design. The foreign-ion doping or substitution is highlighted, involving Na, V, and PO43- sites, which include single-site doping, multiple-site doping, single-ion doping, multiple-ion doping and so on. Furthermore, the challenges and prospects of high-performance NVP cathode material are also put forward. It is believed that this review can provide a useful reference for designing and developing high-performance NVP cathode material toward the large-scale application in SIBs.

Differences in seasonal dynamics and pyrethroid resistance development among Anopheles Hyrcanus group species.

BACKGROUND: The Anopheles Hyrcanus group, which transmits Plasmodium vivax, consists of six confirmed species in South Korea. An epidemiological study revealed differences in the seasonal occurrence patterns of each species. Pyrethroid resistance in An. sinensis dates back to the early 2000s, whereas information on pyrethroid resistance in other species is lacking despite their greater significance in malaria epidemiology. METHODS: Anopheles mosquitoes were collected from two malaria-endemic regions in South Korea for 2 years and their knockdown resistance (kdr) mutations were genotyped. The larval susceptibility to λ-cyhalothrin was compared in six Anopheles species and its seasonal changes in three species were investigated. The full-length sequences of the voltage-sensitive sodium channel (VSSC) were compared across six species to evaluate potential target-site insensitivity. The contribution of the kdr mutation to phenotypic resistance was confirmed by comparing median lethal time (LT50) to λ-cyhalothrin between populations of Anopheles belenrae with distinct genotypes. RESULTS: The composition and seasonal occurrence of rare species (Anopheles kleini, Anopheles lestri, and Anopheles sineroides) varied considerably, whereas An. sinensis occurs continuously throughout the season. A kdr mutation in the form of heterozygous allele was newly identified in An. belenrae, An. lesteri, An. pullus, and An. sineroides. The baseline susceptibility to λ-cyhalothrin was the highest in An. belenrae, followed by An. lesteri, An. sineroides, An. kleini, An. pullus, and An. sinensis, with median lethal concentration (LC50) values ranging from 6.0- to 73.5-fold higher than that of An. belenrae. The susceptibility of An. sinensis and An. pullus varied by season, whereas that of An. belenrae remained stable. The kdr-heterozygous An. belenare population exhibited 5.1 times higher LT50 than that of the susceptible population. Species-specific VSSC sequence differences were observed among the six species. CONCLUSIONS: Our findings suggest that the status and extent of pyrethroid resistance vary among Anopheles Hyrcanus group species. While An. sinensis, the predominant species, developed a considerable level of pyrethroid resistance through kdr mutation, the resistance levels of other species appeared to be less pronounced. Large-scale monitoring is crucial to fully understand species-specific seasonal occurrence and resistance status for effective management strategies, considering the ongoing impact of climate change on their vectorial capacity.

A Comparative Evaluation of the Effect of Different Endodontic Irrigating Solutions on Microhardness of Root Canal Dentin: An in vitro Study.

Statement of the Problem: During endodontic therapy, irrigation solutions applied in the root canal may affect the physicochemical properties of the dentinal wall, thereby changing its microhardness. This may adversely affect the sealing ability and adhesion of dental materials. Therefore, many studies have focused on the search for an ideal root canal irrigant that has a minimal effect on dentinal microhardness. Purpose: This in vitro study was conducted to determine the changes in dentin microhardness after root canal irrigation with different endodontic irrigants. Materials and Method: Ninety-five freshly extracted maxillary central incisor teeth with straight single canals were selected. These teeth were sectioned transversely at the level of the cementoenamel junction. The working length of each tooth was determined, and canal space was prepared by the HyFlex CM rotary file system. During instrumentation, normal saline was used for irrigation. Then, teeth were split longitudinally into two segments. According to the irrigating solution employed, samples were divided into five groups (n=19): normal saline (Group A), 3% sodium hypochlorite (Group B), 2% chlorhexidine (Group C), 5% calcium hypochlorite (Group D), and 0.2% nanochitosan (Group E).3 mL of the corresponding irrigating solution was administered for total15 minutes in each prepared sample. The Vickers micro-hardness tester was then used to assess micro-hardness. The data was analyzed using one-way analysis of variance (ANOVA). Results: All tested irrigating solutions decreased the dentinal microhardness. Samples irrigated with 5% calcium hypochlorite demonstrated dentinal microhardness of 42.43±1.62, which is the lowest among all the tested groups, followed by nano chitosan, sodium hypochlorite, and chlorhexidine. Samples treated with control group (saline) demonstrated the maximum microhardness of dentin in the present study. Conclusion: Within the limitations of this research, it can be concluded that the tested novel irrigating solutions, 5% calcium hypochlorite and 0.2% nanochitosan, were more detrimental to radicular dentin microhardness when compared with conventional endodontic irrigants.

Multifocal Nonmetastatic Radioactive Iodine Avidity on Whole Body Scan After Thyroidectomy for Thyroid Cancer.

Background/Objective: Non-metastatic radioactive iodine (RAI) uptake can complicate the interpretation of whole-body scan (WBS) for differentiated thyroid carcinoma (DTC) post-thyroidectomy. We present a patient with DTC whose follow-up WBS showed nonmetastatic multifocal avidity in skeletal tissue, an uncommonly reported site of RAI uptake. Case report: A 42-year-old woman underwent a right hemithyroidectomy, followed by completion thyroidectomy and RAI remnant ablation therapy, for a 4.8 cm thyroid tumor consistent with stage pT3aNxMx follicular thyroid cancer. Follow-up WBS showed intense activity in the thyroid bed, right breast, left medial subcortical acetabulum, and several vertebral bodies. Her biochemical and clinical findings were not suggestive of cancer recurrence. Further workup with SPECT/CT and MRI showed no focal vertebral lesions and identified the left femoral lesion as a benign peripheral nerve sheath. Diagnostic mammography and ultrasound showed no evidence of suspicious breast lesions. Neck ultrasound was clear with no suspicious masses or pathologic lymphadenopathy. She remained in remission on continued active surveillance. Discussion: Nonmetastatic RAI uptake on WBS has many causes, including functional sodium-iodide symporter expression in nonthyroidal tissues, radioiodine accumulation in tissues and bodily fluids, and benign tumors. False-positive uptake can decrease the utility of post-treatment WBS in low-risk patients. Careful clinical examination, biochemical and radiologic follow-up, and close active surveillance can help distinguish false-positive uptake from metastatic or recurrent disease. Conclusion: We describe an uncommon case of RAI uptake in skeletal tissues after thyroidectomy for DTC, and we outline the steps taken to rule out underlying metastases.

Kinetic properties of gill (Na+, K+)-ATPase in the Pacific whiteleg shrimp Penaeus vannamei (Decapoda, Penaeidae).

The whiteleg marine shrimp Penaeus vannamei, originally from the Eastern Pacific Ocean, now inhabits tropical waters across Asia and Central and Southern America. This benthic species exhibits rapid growth, wide salinity and temperature tolerance, and disease resistance. These physiological traits have led to extensive research on its osmoregulatory mechanisms, including next-generation sequencing, transcriptomic analyses, and lipidomic responses. In crustaceans, osmotic and ionic homeostasis is primarily maintained by the membrane-bound metalloenzyme (Na+, K+)-ATPase. However, little is known about how various ligands modulate this enzyme in P. vannamei. Here, we examined the kinetic characteristics of the gill (Na+, K+)-ATPase to get biochemical insights into its modulation. A prominent immunoreactive band of ~120 kDa, corresponding to the (Na+, K+)-ATPase alpha-subunit, was identified. The enzyme exhibited two ATP hydrolyzing sites with K0.5 = 0.0003 ±â€¯0.00002 and 0.05 ±â€¯0.003 mmol L-1 and was stimulated by low sodium ion concentrations. Potassium and ammonium ions also stimulated enzyme activity with similar K0.5 values of 0.08 ±â€¯0.004 and 0.06 ±â€¯0.003 mmol L-1, respectively. Ouabain inhibition profile suggested a single enzyme isoform with a KI value of 2.10 ±â€¯0.16 mmol L-1. Our findings showed significant kinetic differences in the (Na+, K+)-ATPase in Penaeus vannamei compared to marine and freshwater crustaceans. We expect our results to enhance understanding of the modulation of gill (Na+, K+)-ATPase in Penaeus vannamei and to provide a valuable tool for studying the shrimp's biochemical acclimation to varying salinity conditions.

Discovery of Knock-Down Resistance in the Major African Malaria Vector Anopheles funestus.

A major insecticide resistance mechanism in insect pests is knock-down resistance (kdr) caused by mutations in the voltage-gated sodium channel (Vgsc) gene. Despite being common in most malaria Anopheles vector species, kdr mutations have never been observed in Anopheles funestus, the principal malaria vector in Eastern and Southern Africa, with resistance mainly being conferred by detoxification enzymes. In a parallel study, we monitored 10 populations of An. funestus in Tanzania for insecticide resistance unexpectedly identified resistance to a banned insecticide, DDT, in the Morogoro region. Through whole-genome sequencing of 333 An. funestus samples from these populations, we found eight novel amino acid substitutions in the Vgsc gene, including the kdr variant, L976F (equivalent to L995F in An. gambiae), in tight linkage disequilibrium with another (P1842S). The mutants were found only at high frequency in one region and were accompanied by weak signatures of a selective sweep, with a significant decline between 2017 and 2023. Notably, kdr L976F was strongly associated with survivorship to exposure to DDT insecticide, while no clear association was noted with a pyrethroid insecticide (deltamethrin). The WHO prequalifies no DDT products for vector control, and the chemical is banned in Tanzania. Widespread DDT contamination and a legacy of extensive countrywide stockpiles may have selected for this mutation. Continued monitoring is necessary to understand the origin of kdr in An. funestus, and the threat posed to insecticide-based vector control in Africa.

Alpha-adducin 1 (rs4961) gene and its expression associated with sodium sensitivity in hypertensive patients: a cohort study in the western Ukrainian population.

Objective. The aim of this study was to evaluate the association of the α-adducin-1 gene (ADD1) (Gly460Trp [rs4961]) polymorphism and its expression in association with renal dysfunction and sodium sensitivity in hypertensive patients in western Ukrainian population. Methods. One-hundred patients with essential arterial hypertension (EAH) and hypertensive-mediated target organ damage (stage 2), moderate, high, and very high cardiovascular risk were enrolled in case-control study. Sixty healthy individuals were assigned as controls. Sodium sensitivity and sodium resistance were determined by salt load reaction. The ADD1 (rs4961) genotyping was performed in RT-PCR. Results. The expression of the quantitative trait loci (eQTL) of ADD1 gene (rs4961) (chr4:2906707 [hg19]) was confirmed in 37 tissues and organs with 23 phenotypic traits. Two hundred eQTL associations revealed - all cis-variants (cis-QTL); 73 methylation QTL (mQTL), 34 splicing QTL (sQTL), 14 histone modification QTL (hQTL), 2 protein QTL (pQTL), 23 transcript utilization QTL (tuQTL), and 4 loci of incorporated long noncoding areas of RNA (lncRNA). GG-genotype unreliably enhances EAH risk (OR=1.92; 95%CI: 0.90-4.10; p=0.066). Sodium sensitivity was observed in 54.0% of patients and in 20.0% of controls (c2=17.89; p<0.001). Sodium sensitivity in T-allele carriers of the ADD1 gene (1378G>T; rs4961) dominated 12-fold in general (OR 95%CI: 2.24-64.29; p=0.001), in women - 4.71 times (OR 95%CI: 1.92-11.56; p<0.001), and in men - 4.09 times (OR 95%CI: 1.03-16.28; p=0.041). Sodium sensitivity elevated the likelihood of severe EAH twice (OR=2.19; OR 95%CI: 1.00-5.05; p=0.049). Conclusion. T-allele associates with sodium sensitivity in essential arterial hypertension patients and increases the risk of hypertension regardless the gender. Sodium sensitivity enhances the probability of severe essential arterial hypertension in observed population.

Exploring SGLT-2 inhibitors and sarcopenia in FAERS: a post-marketing surveillance study.

BACKGROUND: The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear. RESEARCH DESIGN AND METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs. RESULTS: The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use. CONCLUSIONS: Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

Practical use and target value of urine sodium-to-potassium ratio in assessment of hypertension risk for Japanese: Consensus Statement by the Japanese Society of Hypertension Working Group on Urine Sodium-to-Potassium Ratio.

Epidemiological studies have demonstrated that the urine sodium-to-potassium (Na/K) ratio is more positively associated with high blood pressure and cardiovascular disease risk than either urine sodium or potassium excretion alone. In this consensus statement, we recommend using the average Na/K ratio of casual urines randomly taken in various times on at least four days a week for a reliable individual estimate because of high day-to-day and intraday variability of casual urine Na/K ratio within individuals. Although a continuous positive association exists between the Na/K ratio and high blood pressure or cardiovascular disease risk, for clinical and public health decision making for Japanese, we recommend using an average urine Na/K ratio of 2 as an optimal target value because this aligns with recommendations for both sodium and potassium intake in the Dietary Reference Intakes for Japanese, 2020, considering a typical Japanese dietary pattern. We also suggest that an average urine Na/K ratio of 4 is a feasible target value to achieve a temporary goal of being below the mean values of the urine Na/K ratio across Japanese general populations. These recommendations apply mainly for apparently healthy individuals, but not for patients with specific conditions due to the lack of supporting data. Current evidence for the usefulness of measuring the urine Na/K ratio for the prevention or control of hypertension remains inconclusive and warrants further investigation.

Statistics design for the synthesis optimization of lignin-sulfonate sulfur-doped mesoporous carbon materials: promising candidates as adsorbents and supercapacitors materials.

This study employed lignin-sulfonated (LS) to develop biobased carbon materials (LS-Cs) through a sulfur-doping approach to enhance their physicochemical properties, adsorption capabilities, and energy storage potentials. Various characterization techniques, including BET surface area analysis, SEM imaging, XPS, Raman spectroscopy, and elemental composition (CHNS), were employed to assess the quality of the LS-Cs adsorbent and electrode samples. Response Surface Methodology (RSM) was utilized for optimizing the two main properties (specific surface area, ABET, and mesopore area, AMESO) by evaluating three independent factors (i.e., activation temperature, ZnCl2:LS ratio, and sulfur content). According to the statistical analysis, ABET and AMESO were affected by ZnCl2 and sulfur content, while the pyrolysis temperature did not affect the responses in the studied conditions. It was found that increasing the ZnCl2 and sulfur contents led to an increment of the ABET and AMESO values. The LS-C materials exhibited very high ABETvalues up to 1993 m2 g-1 and with predominantly mesoporous features. The S-doping resulted in LS-Cs with high sulfur contents in their microstructures up to 15% (wt%). The LS-C materials were tested as adsorbents for sodium diclofenac (DCF) adsorption and reactive orange 16 dye (RO-16) and as electrodes for supercapacitors. The LS-Cs exhibited excellent adsorption capacity values for both molecules (197-372 mg g-1) for DCF, and (223-466 mg g-1) for RO-16. When tested as electrodes for supercapacitors, notably, LS-C3, which is a doped sample with sulfur, exhibited the best electrochemical performance, e.g. high specific capacitance (156 F/g at 50 mV/s), and delivered an excellent capacitance after 1000 cycles (63 F/g at 1 A/g), which denotes the noteworthy capacitive behavior of the S-doped electrode. Thus, the present work suggests an eco-friendly resource for developing effective, productive carbon materials for adsorbent and electrodes for SC application. However, further studies on the complete application of these materials as adsorbents and electrodes are needed for a deeper understanding of their behavior in environmental and energy storage applications.