Metal- and solvent-free domino reaction of 2-isocyanophenol esters to benzoxazines: long-range 1,5-acyl migration on 1,4-diazabutatriene.

The first example of intramolecular nucleophilic addition of 1,4-diazabutatriene to ester is disclosed. This approach provides a facile and versatile synthesis for functionalized 2H-1,4-benzoxazines under metal-, reagent-, and solvent-free conditions. Experimental and computational studies revealed the pivotal role of 1,5-acyl migration as the self-catalytic step in the reaction selectivity.

Redefining the concept of residual renal function with kidney sodium MRI: a pilot study.

RATIONALE & OBJECTIVE: The concept of residual kidney function (RKF) is exclusively based upon urine volume and small solute clearance, making RKF challenging to assess in clinical practice. The aim of this study was to test the technical feasibility of obtaining useable 23Na-MRI kidney images in hemodialysis (HD) participants. STUDY DESIGN: We conducted an exploratory prospective study to quantify the cortico-medullary sodium gradient in healthy and HD participants. Participants fasted for eight hours prior to their study visit. Urine samples were collected to measure urinary osmolarity, before MRI. Proton and sodium pictures were merged; ROIs were delineated for the medulla and cortex when feasible. In cases where cortex could not be identified, we considered the cortico to medulla gradient (CMG) to be no longer present, resulting in a medulla-to-cortex ratio of 1. SETTING & PARTICIPANTS: 17 healthy volunteers and 21 HD participants. FINDINGS: Median (IQR) fasting medulla to cortex ratio was significantly higher 1.56 [1.5-1.61] in healthy volunteers compared to HD patients 1.22 [1.13-1.3], p < 0.0001. Medulla to cortex ratio and median urinary osmolarity were correlated (r = 0.87, p < 0.0001) in the whole population. We found a significant association between HD vintage and medulla to cortex ratio whereas we did not find any association with urine volume. Sodium signal intensity distribution within healthy kidney describes two different peaks- relating to well defined cortex and medulla; whereas HD participants displays only a single peak indicative of the markedly lower sodium concentration. LIMITATIONS: This study is only an exploratory study with a modest number of patients. CONCLUSIONS: the application of kidney sodium MRI to the study of RKF in patients receiving maintenance HD is practical and provides a previously unavailable ability to interrogate the function of remnant tubular function.

Positive correlation between echocardiographic tricuspid E peak velocity and central venous pressure in dogs: A preliminary study.

In the absence of vascular obstruction, central venous pressure (CVP) is a hydrostatic pressure in the cranial and caudal vena cava, providing valuable information about cardiac function and intravascular volume status. It is also a component in evaluating volume resuscitation in patients with septic shock and monitoring patients with right heart disease, pericardial disease, or volume depletion. Central venous pressure is calculated in dogs by invasive central venous catheterization, which is considered high-risk and impractical in critically ill patients. This study aimed to investigate the feasibility of using echocardiographic tricuspid E/E' as a noninvasive method to estimate CVP in anesthetized healthy dogs under controlled hypovolemic conditions. Ten male mixed-breed dogs were included in the study after a thorough health assessment. For hypovolemia induction, blood withdrawal was performed, and echocardiographic factors of the tricuspid valve, including peak E and E' velocities, were measured during CVP reduction. Repeated measures analysis of variance and Bonferroni post hoc tests were employed to compare the average difference between measured echocardiographic indices and CVP values derived from catheterization and intermittent measurement methods. Spearman's ρ correlation coefficient was used to evaluate the correlation between echocardiographic indices and CVP. E peak velocity had a significant negative correlation with venous blood pressure phases (r = -0.44, P = .001), indicating a decrease in peak E velocity with progressive CVP reduction. However, tricuspid valve E' peak velocity and E/E' did not correlate with CVP, suggesting that these parameters are not reliable for CVP estimation in dogs.

Reassuring Data on the Cardiovascular Risk in Adults With X-linked Hypophosphatemia Receiving Conventional Therapy.

CONTEXT: X-linked hypophosphatemia (XLH) is a rare genetic disorder that results in increased plasma levels of fibroblast growth factor 23 (FGF23). Several studies have demonstrated a direct association between FGF23 and cardiovascular mortality in cohorts of patients with chronic renal failure. However, in patients with XLH, studies on the cardiovascular impact of the disease are rare, with contradictory results. OBJECTIVE: The aim was to assess whether the disease led to an increased cardiovascular risk. METHODS: We conducted a single-center retrospective observational study on a local cohort of adult patients with XLH. The primary endpoint was a composite endpoint of the frequency of left ventricular hypertrophy (LVH) or presence of high blood pressure. Our secondary objectives were to assess echocardiographic, pulse wave velocity, and central blood pressure data as other markers of CV health. Independently of this cohort, tissue sodium content with magnetic resonance imaging was studied in 2 patients with XLH before and after burosumab. RESULTS: Twenty-two patients were included. Median serum phosphate was 0.57 (0.47-0.72) mmol/L and FGF23 94 pg/L (58-2226). Median blood pressure was 124 (115-130)/68 (65-80) mm Hg, with only 9% of patients being hypertensive. A majority of patients (69%) had no LVH, only 1 had a left ventricular mass >100 g/m² and 25% of patients had left ventricular remodeling. Pulse wave velocity was normal in all patients. No differences in skin and muscle sodium content were observed before and after burosumab in the 2 patients who underwent sodium magnetic resonance imaging. CONCLUSION: We found no elevated risk of developing hypertension or LVH in patients with XLH.

Recent Advances in Sodium Magnetic Resonance Imaging and Its Future Role in Kidney Disease.

Sodium imbalance is a hallmark of chronic kidney disease (CKD). Excess tissue sodium in CKD is associated with hypertension, inflammation, and cardiorenal disease. Sodium magnetic resonance imaging (23Na MRI) has been increasingly utilized in CKD clinical trials especially in the past few years. These studies have demonstrated the association of excess sodium tissue accumulation with declining renal function across whole CKD spectrum (early- to end-stage), biomarkers of systemic inflammation, and cardiovascular dysfunction. In this article, we review recent advances of 23Na MRI in CKD and discuss its future role with a focus on the skin, the heart, and the kidney itself.

Genome-wide transcriptional profiling provides clues to molecular mechanisms underlying cold tolerance in chickpea.

Chickpea is an important food legume cultivated in several countries. A sudden drop in autumn temperature, freezing winter temperature, and late spring cold events result in significant losses in chickpea production. The current study used RNA sequencing of two cold tolerant (Saral) and sensitive (ILC533) Kabuli chickpea genotypes to identify cold tolerance-associated genes/pathways. A total of 200.85 million raw reads were acquired from the leaf samples by Illumina sequencing, and around 86% of the clean reads (199 million) were mapped to the chickpea reference genome. The results indicated that 3710 (1980 up- and 1730 down-regulated) and 3473 (1972 up- and 1501 down-regulated) genes were expressed differentially under cold stress in the tolerant and sensitive genotypes, respectively. According to the GO enrichment analysis of uniquely down-regulated genes under cold stress in ILC533, photosynthetic membrane, photosystem II, chloroplast part, and photosystem processes were enriched, revealing that the photosynthesis is severely sensitive to cold stress in this sensitive genotype. Many remarkable transcription factors (CaDREB1E, CaMYB4, CaNAC47, CaTCP4, and CaWRKY33), signaling/regulatory genes (CaCDPK4, CaPP2C6, CaMKK2, and CaHSFA3), and protective genes (CaCOR47, CaLEA3, and CaGST) were identified among the cold-responsive genes of the tolerant genotype. These findings would help improve cold tolerance across chickpea genotypes by molecular breeding or genetic engineering.

Magnetic excitations in the helical Rashba superconductor.

We investigate the magnetic excitation spectrum in the helical state of a noncentrosymmetric superconductor with inversion symmetry breaking and strong Rashba spin-orbit coupling. For this purpose we derive the general expressions of the dynamical spin response functions under the presence of strong Rashba splitting of conduction bands, superconducting gap and external field which lead to stabilization of Cooper pairs with finite overall momentum in a helical state. The latter is characterized by momentum space regions of paired and unpaired states with different quasiparticle dispersions. The magnetic response is determined by i) excitations within and between both paired and unpaired regions ii) anomalous coherence factors and iii) additional spin matrix elements due to helical Rashba spin texture of bands. We show that as a consequence typical correlated real space and spin space anisotropies appear in the dynamical susceptibility which would be observable as a characteristic fingerprint for a helical superconducting state in inelastic neutron scattering investigations.

In vitro cytotoxicity, antibacterial activity and HSA and ct-DNA interaction studies of chlorogenic acid loaded on γ-Fe2O3@SiO2 as new nanoparticles.

In this study, nanoparticles with both anticancer and antibacterial features were synthesized through loading chlorogenic acid (CGA) of essential oils on magnetic nanoparticles (MNPs). Characterization of γ-Fe2O3@SiO2-CGA MNPs was performed using Fourier transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM) that show effective coating of the MNPs with SiO2 and CGA ligand and spherical shape of the nanoparticles with a mean diameter of 16 nm, respectively. The cytotoxicity study demonstrated that γ-Fe2O3@SiO2-CGA MNPs had fewer toxic effects on normal cells (Huvec) than on cancerous cells (U-87 MG, A-2780 and A-549), and could be a new potential candidate for use in biological and pharmaceutical applications. The interaction of calf thymus deoxyribonucleic acid (ct-DNA) with γ-Fe2O3@SiO2-CGA MNPs indicated that the anticancer activity might be associated with the DNA binding properties of γ-Fe2O3@SiO2-CGA MNPs. Moreover, the interaction of γ-Fe2O3@SiO2-CGA MNPs with human serum albumin (HSA) suggests that the native conformation of HSA was preserved at the level of secondary structure, indicating that the γ-Fe2O3@SiO2-CGA MNPs do not show any cytotoxicity effect when they are injected into the blood. Antibacterial tests were performed and represented γ-Fe2O3@SiO2-CGA MNPs attained better antibacterial function than CGA as free.

Effects of pediatric chronic kidney disease and its etiology on tissue sodium concentration: a pilot study.

BACKGROUND: Sodium-23 magnetic resonance imaging (23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na+] compared to healthy controls. METHODS: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg 23Na MRI for tissue [Na+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na+] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na+] and kidney function. RESULTS: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na+] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na+] Z-scores. Reduced whole-leg [Na+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na+] measures were significantly associated with proteinuria and hypoalbuminemia. CONCLUSIONS: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na+] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information.

Outcomes and predictors of skin sodium concentration in dialysis patients.

Background: Sodium-23 magnetic resonance imaging (23Na MRI) allows the measurement of skin sodium concentration ([Na+]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition. Methods: This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na+] quantification with leg 23Na MRI at the study's beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan-Meier survival function after stratification into skin [Na+] quartiles. Cox proportional hazards regression was used to model the association between skin [Na+] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na+]. Results: A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353-602). Increasing skin [Na+] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ2(1) = 3.926, log-rank χ2(1) = 5.685; P for trend <0.05 in both instances). Skin [Na+] was associated with all-cause mortality {hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988-8.101]; P < 0.001} and composite events [HR 2.332 (95% CI 1.378-3.945); P < 0.01], independently of age, sex, serum [Na+] and albumin. In multiple regression models, dialysate [Na+], serum albumin and congestive heart failure were significantly associated with skin [Na+] in HD patients (R2 adj = 0.62). Conclusions: Higher skin [Na+] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.

Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys.

Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups (r2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 (P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Laustsen and Bøgh in this issue.

Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?

BACKGROUND: Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. METHODS: We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. RESULTS: There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23-37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22-35] mmol/L), P=0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19-26] mmol/L), P=0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P=0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium (P=0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% (P=0.03). CONCLUSIONS: We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03004547.

Green synthesis of colloidal selenium nanoparticles in starch solutions and investigation of their photocatalytic, antimicrobial, and cytotoxicity effects.

In this research, we have offered a green and new synthesizing procedure for selenium nanoparticles (Se-NPs) through the utilization of Na2SeO3, in which starch has a role of stabilizer and capping agent, as the functionality of green reducing mediums is taken by glucose and ascorbic acid. According to the observations, this method has been capable of producing Se-NPs in lab conditions. Additionally, the synthesized Se-NPs can be separated from the aqueous solution of stabilizer and reducing agents by a high-speed. Certain analyzing procedures have been used to characterize the obtained particles including TEM, XRD, UV-VIS, DLS, FESEM, EDX, FTIR, and AFM. In this paper, we have investigated the antimicrobial and photocatalytic functionality of Se-NPs on Mycobacterium tuberculosis and Methylene blue (MB) and according to the results, these particles have shown satisfying activity in both cases. To be stated in exact, about 60% of MB has degraded under UV light after 150 min, which indicates the acceptable position of Se-NPs could be applied for eliminating water pollutions. Moreover, the attained data on colorectal cancer SW480 cell lines in regards to the in vitro cytotoxicity assessments have exhibited non-toxic effects, which had lasted throughout concentrations that had measured up to even 100 µg/mL within MTT assay.

Spatially dispersing Yu-Shiba-Rusinov states in the unconventional superconductor FeTe0.55Se0.45.

By using scanning tunneling microscopy (STM) we find and characterize dispersive, energy-symmetric in-gap states in the iron-based superconductor FeTe0.55Se0.45, a material that exhibits signatures of topological superconductivity, and Majorana bound states at vortex cores or at impurity locations. We use a superconducting STM tip for enhanced energy resolution, which enables us to show that impurity states can be tuned through the Fermi level with varying tip-sample distance. We find that the impurity state is of the Yu-Shiba-Rusinov (YSR) type, and argue that the energy shift is caused by the low superfluid density in FeTe0.55Se0.45, which allows the electric field of the tip to slightly penetrate the sample. We model the newly introduced tip-gating scenario within the single-impurity Anderson model and find good agreement to the experimental data.

Pruritus: Is there a grain of salty truth?

Hemodialysis patients characteristically suffer from a range of unpleasant symptoms. Uremic pruritus effects close to half of the chronic kidney disease population, reducing quality of life and associated with increased mortality. Its pathophysiology though is poorly understood; currently deployed therapeutic approaches are ineffective. Excessive levels of skin and soft tissue sodium accumulate in dialysis patients, producing a range of biological consequences, including inflammation. We report an index case of a hemodialysis patient with debilitating pruritus and extreme levels of tissue sodium, measured with Sodium-23 magnetic resonance imaging. Both the tissue sodium loading and pruritus responded fully to initiation of expanded hemodialysis therapy with a recently introduced medium cutoff dialysis membrane-based dialyzer.

Corrigendum to "Plant growth promoting Streptomyces strains are selectively interacting with the wheat cultivars especially in saline conditions" [Heliyon 6 (2) (2020) e03445].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03445.].

Tissue sodium concentrations in chronic kidney disease and dialysis patients by lower leg sodium-23 magnetic resonance imaging.

BACKGROUND: Sodium-23 magnetic resonance imaging (23Na MRI) allows direct measurement of tissue sodium concentrations. Current knowledge of skin, muscle and bone sodium concentrations in chronic kidney disease (CKD) and renal replacement therapy patients is limited. In this study we measured the tissue sodium concentrations in CKD, hemodialysis (HD) and peritoneal dialysis (PD) patients with 23Na MRI of the lower leg and explored their correlations with established clinical biomarkers. METHODS: Ten healthy controls, 12 CKD Stages 3-5, 13 HD and 10 PD patients underwent proton and 23Na MRI of the leg. The skin, soleus and tibia were segmented manually and tissue sodium concentrations were measured. Plasma and serum samples were collected from each subject and analyzed for routine clinical biomarkers. Tissue sodium concentrations were compared between groups and correlations with blood-based biomarkers were explored. RESULTS: Tissue sodium concentrations in the skin, soleus and tibia were higher in HD and PD patients compared with controls. Serum albumin showed a strong, negative correlation with soleus sodium concentrations in HD patients (r = -0.81, P < 0.01). Estimated glomerular filtration rate showed a negative correlation with tissue sodium concentrations (soleus: r = -0.58, P < 0.01; tibia: r = -0.53, P = 0.01) in merged control-CKD patients. Hemoglobin was negatively correlated with tissue sodium concentrations in CKD (soleus: r = -0.65, P = 0.02; tibia: r = -0.73, P < 0.01) and HD (skin: r = -0.60, P = 0.04; tibia: r = -0.76, P < 0.01). CONCLUSION: Tissue sodium concentrations, measured by 23Na MRI, increase in HD and PD patients and may be associated with adverse metabolic effects in CKD and dialysis.

Tragacanth-mediate synthesis of NiO nanosheets for cytotoxicity and photocatalytic degradation of organic dyes.

In this study, NiO nanosheets have been manufactured using a co-precipitation approach that involved the usage of nickel nitrate (Ni (NO3)2.6H2O) as the raw material and tragacanth in the role of a stabilizing agent. NiO nanosheets have been fabricated through the reduction of nickel nitrate solution that had been obtained by the application of aqueous extract of tragacanth, which is capable of functioning as a reducing and stabilizing agent. In the following, the physical and chemical properties of tragacanth-stabilized NiO nanosheets have been identified via FESEM, EDS, XRD, UV-Vis, and FT-IR techniques. According to the XRD pattern, these particular nanosheets have contained a cubic structure and group space Fm3m, along with the average size of about 18 to 43 nm that had been in agreement with the FESEM measurements. In addition, we have evaluated the photocatalytic activity of tragacanth-stabilized NiO nanosheets on the degradations of methylene blue (MB) and methyl orange (MO) dyes. The performed photocatalytic assessment has displayed that the nanosheets can degrade 82% of MO within 210 min and 60% of MB in 300 min. The cytotoxicity of tragacanth-stabilized NiO nanosheets on human Glioblastoma cancer (U87MG) cell lines has been investigated via the MTT assay, while it has been detected in the obtained results that the inhibitory concentration (IC50) had been 125 µg/mL.