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Transient receptor potential canonical 6 (TRPC6) variants, which were initially detected in adult-onset familial focal segmental glomerulosclerosis (FSGS), were also identified in pediatric-onset one. Here, we present a patient with adult-onset steroid-resistant nephrotic syndrome (SRNS) who harbored a likely pathogenic TRPC6 variant and partially responded to calcineurin inhibitors (CNIs). A 44-year-old woman with stable rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome was presented with nephrotic syndrome. Her renal biopsy results showed minor glomerular abnormalities. Upon admission, she was treated with steroids for around 4 weeks, but it was ineffective. After 1-2 weeks of cyclosporine A (CyA) administration, urine output increased, renal function improved without a decrease in proteinuria, and she was discharged. Her renal function was maintained for 2 months, but after a CyA dose reduction, she was again admitted to the hospital due to relapsing edema, decreased urine output, and worsening renal function. CyA was replaced by tacrolimus (TAC). A second renal biopsy showed nearly the same findings as the first except for tubulointerstitial lesions. After 1-2 weeks of TAC administration, urine output increased, and renal function improved. However, urinary protein levels did not decrease as before. After discharge, a whole exome analysis revealed a heterozygous splice donor site variant NM_004621.6;c.2644 + 1G > A in TRPC6. Genetic testing identified a novel splice donor site variant of TRPC6 in a patient with adult-onset SRNS, which prevented unnecessary steroid continuation. The safety and efficacy of CNI in TRPC6 glomerulopathy must be evaluated in future larger studies with longer follow-up., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Nicotinamide adenine dinucleotide (NAD + ) is a universal coenzyme regulating cellular energy metabolism in many cell types. Recent studies have demonstrated the close relationships between defective NAD + metabolism and aging and age-associated metabolic diseases. The major purpose of the present study was to test the hypothesis that NAD + biosynthesis, mediated by a rate-limiting NAD + biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT), is essential for maintaining normal adipose tissue function and whole body metabolic health during the aging process. To this end, we provided in-depth and comprehensive metabolic assessments for female adipocyte-specific Nampt knockout (ANKO) mice during aging. We first evaluated body fat mass in young (≤4-mo-old), middle aged (10-14-mo-old), and old (≥18-mo-old) mice. Intriguingly, adipocyte-specific Nampt deletion protected against age-induced obesity without changing energy balance. However, data obtained from the hyperinsulinemic-euglycemic clamp procedure (HECP) demonstrated that, despite the lean phenotype, old ANKO mice had severe insulin resistance in skeletal muscle, heart, and white adipose tissue (WAT). Old ANKO mice also exhibited hyperinsulinemia and hypoadiponectinemia. Mechanistically, loss of Nampt caused marked decreases in WAT gene expression of lipogenic targets of peroxisome proliferator-activated receptor gamma (PPAR-γ) in an age-dependent manner. In addition, administration of a PPAR-γ agonist rosiglitazone restored fat mass and improved metabolic abnormalities in old ANKO mice. In conclusion, these findings highlight the importance of the NAMPT-NAD + -PPAR-γ axis in maintaining functional integrity and quantity of adipose tissue, and whole body metabolic function in female mice during aging. NEW & NOTEWORTHY Defective NAD + metabolism is associated with aging and age-associated metabolic diseases. In the present study, we provided in-depth metabolic assessments in female mice with adipocyte-specific inactivation of a key NAD + biosynthetic enzyme NAMPT and revealed an unexpected role of adipose tissue NAMPT-NAD + -PPAR-γ axis in maintaining functional integrity and quantity of adipose tissue and whole body metabolic health during the aging process.

Objective: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients., Methods: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men)., Results: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (β = -0.26, P < 0.001), RRI (β = 0.17, P = 0.022), global glomerular sclerosis (β = 0.21, P = 0.002), and IFTA (β = 0.17, P = 0.012)., Conclusion: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

This research aims to elucidate the physiological mechanisms behind the accidental acquisition of high-concentration cesium ions (Cs + ) tolerance of Escherichia coli and apply this understanding to develop bioremediation technologies. Bacterial Cs + resistance has attracted attention, but its physiological mechanism remains largely unknown and poorly understood. In a prior study, we identified the Cs + /H + antiporter TS&#95;CshA in Microbacterium sp. TS-1, resistant to high Cs + concentrations, exhibits a low Cs + affinity with a K m value of 370 mM at pH 8.5. To enhance bioremediation efficacy, we conducted random mutagenesis of TS&#95;cshA using Error-Prone PCR, aiming for higher-affinity mutants. The mutations were inserted downstream of the P BAD promoter in the pBAD24 vector, creating a mutant library. This was then transformed into E. coli -competent cells. As a result, we obtained a Cs + -resistant strain, ZX-1, capable of thriving in 400 mM CsCl-a concentration too high for ordinary E. coli . Unlike the parent strain Mach1 ™ , which struggled in 300 mM CsCl, ZX-1 showed robust growth even in 700 mM CsCl. After 700 mM CsCl treatment, the 70S ribosome of Mach1 ™ collapsed, whereas ZX-1 and its derivative ΔZX-1/pBR322ΔAp remained stable. This means that the ribosomes of ZX-1 are more stable to high Cs + . The inverted membrane vesicles from strain ZX-1 showed an apparent K m value of 28.7 mM (pH 8.5) for Cs + /H + antiport activity, indicating an approximately 12.9-fold increase in Cs + affinity. Remarkably, the entire plasmid isolated from ZX-1, including the TS&#95;cshA region, was mutation-free. Subsequent whole-genome analysis of ZX-1 identified multiple SNPs on the chromosome that differed from those in the parent strain. No mutations in transporter-related genes were identified in ZX-1. However, three mutations emerged as significant: genes encoding the ribosomal bS6 modification enzyme RimK, the phage lysis regulatory protein LysB, and the flagellar base component protein FlgG. These mutations are hypothesized to affect post-translational modifications, influencing the K m value of TS&#95;CshA and accessory protein expression. This study unveils a novel Cs + resistance mechanism in ZX-1, enhancing our understanding of Cs + resistance and paving the way for developing technology to recover radioactive Cs + from water using TS&#95;CshA-expressing inverted membrane vesicles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kojima, Tanaka, Kurosaki, Zhiyu and Ito.)

Context: Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear., Objective: We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes., Methods: We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men)., Results: RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group ( P < .05). RSF% was greater in men than in women ( P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients., Conclusion: Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

A decreased body mass index (BMI) over time is associated with a poor prognosis for patients on hemodialysis. We aimed to examine whether this association also applies to patients with peritoneal dialysis (PD). BMI change was defined as the percentage change in the BMI between the time of PD catheter insertion and six months after its insertion. The association between the BMI change and all-cause mortality or PD discontinuation from six months after PD catheter insertion until October 2021 was investigated. This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (21.2-78.8) months. The median six-month percentage change in the BMI was -2.14 (-5.56-1.84)%, and patients were categorized into tertiles based on their BMI changes. The fully-adjusted Cox regression analysis revealed a significantly higher rate of PD discontinuation or all-cause mortality (hazard ratio (HR): 2.48; 95%; confidence interval (CI): 1.41-4.37) in patients with the lowest tertile (T1, BMI change: < -4.13%) compared to patients with the middle tertile (T2, BMI change: -4.13%-0.67%). The risk was not significantly higher in patients with the highest tertile (T3, BMI change: >0.67%) than those in the T2 group (HR: 1.18; 95% CI: 0.66-2.11). A decreased BMI over time is independently associated with HD transfer or all-cause mortality among patients initiating PD, which highlights the importance of the 6-month BMI change as a novel prognostic marker.

We present a case of life-threatening gastrointestinal bleeding caused by a penetrating atherosclerotic ulcer (PAU) that ruptured into the esophagus. A 65-year-old man presented with pyrexia and nausea. Contrast-enhanced computed tomography (CT) performed on admission revealed a hematoma between the lower esophagus and descending aorta due to a contained rupture of a PAU, which was undiagnosed at that time. Esophagogastroduodenoscopy (EGD) performed on the fifth day of admission revealed a subepithelial lesion in the lower esophagus, further complicated by ulcer formation. Biopsy did not reveal any malignant findings. On the eighth day of admission, the patient experienced substantial hematemesis with vital signs indicative of shock. Emergency EGD was performed, which revealed life-threatening bleeding in the lower esophagus. Contrast-enhanced CT revealed an aortoesophageal fistula with massive hematemesis, after which the patient died. An autopsy revealed perforation of the PAU into the esophagus without aortic dissection or a true aneurysm.Patients with atherosclerosis who develop recent-onset gastrointestinal symptoms, progressive anemia, and/or periaortic lesions should be carefully evaluated using contrast-enhanced CT, and PAU should be considered in the differential diagnosis., (© 2023. Japanese Society of Gastroenterology.)

Introduction: We aimed to determine the correlation between the serum urea-to-creatinine ratio and residual kidney function (RKF) in patients undergoing peritoneal dialysis (PD), as well as its predictive value for PD-related outcomes., Methods: This study included a cross-sectional study to assess the correlation between serum urea-to-creatinine ratio and RKF in 50 patients on PD and a retrospective cohort study to assess the association between serum urea-to-creatinine ratio and PD-related outcomes in 122 patients who initiated PD., Results: Serum urea-to-creatinine ratios had significant positive correlations with renal Kt/V and creatinine clearance values (r = 0.60, p < 0.001 and r = 0.61, p < 0.001, respectively). Additionally, serum urea-to-creatinine ratio was significantly associated with a lower risk of transfer to hemodialysis or PD/hemodialysis hybrid therapy (hazard ratio: 0.84, 95% confidence interval: 0.75-0.95)., Conclusion: The serum urea-to-creatinine ratio can be an indicator of RKF and a prognostic factor in patients undergoing PD., (© 2023 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

We present the description of the new suctorian genus Copterus gen. n. with type species Copterus tyloloricatus sp. n. from the family Acinetidae, inhabiting the prosomes and urosomes of calanoid copepods from the northern North Pacific Ocean. The new taxon is characterized by (i) an ellipsoidal to triangular, asymmetric, dorsoventrally flattened cell body, which lies horizontally on the lorica surface; (ii) an unflattened lorica; and (iii) the presence of three to five radially arranged bundles of tentacles positioned at the edge of the body or on actinophores., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD + ) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD + biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD + concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD + concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function., Objective: This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan., Methods: UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration., Results: Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 m 2 ). The pre- and post-tolvaptan 24-h UVs were significantly higher in patients not administered thiazide diuretics (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day; p < 0.001) than in those administered thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day; p = 0.93). In a multivariate regression model, thiazide diuretic use was significantly associated with decreased 24-h UV (β coefficient - 486.7, 95% confidence interval [CI] - 674.5 to - 298.8); increased urine osmolality (β coefficient 37.7, 95% CI 17.1-58.4); increased body weight (β coefficient 0.62, 95% CI 0.31-0.92); and increased 30-day dialysis initiation rate (odds ratio 3.40, 95% CI 1.18-9.82) after tolvaptan administration., Conclusions: Tolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use., (© 2022. The Author(s).)

Black carbon (BC) is a pyrolyzed product derived from incomplete combustion. A major fraction of BC produced by landscape fires is initially deposited onto onsite soils. Atmospheric deposition of soot is known to be an important source of soil BC, especially in watersheds that are not affected by landscape fires. The transport of the dissolved fraction of oxidized BC in soil, defined as dissolved black carbon (DBC), to streams is considered one of the important loss pathways of BC in soil, but the mechanism is not well documented. We measured the quantity and quality of DBC, determined by a benzenepolycarboxylic acid method, and the quantitative and qualitative parameters of bulk dissolved organic matter (DOM) in streams in Hokkaido, northern Japan, whose catchments were not affected by landscape fire for at least 110 years. DBC with relatively low polycondensed signatures occurred in the streams, irrespective of differences in watershed characteristics and seasons, suggesting that atmospheric deposition of soot into the catchment is probably a major source of stream DBC. The DBC concentration was linearly related to the dissolved organic carbon (DOC) concentration, irrespective of the differences in watershed characteristics and seasons. Furthermore, the polycondensation degree of DBC was observed to correlate with the qualitative parameters of bulk DOM. Such quantitative and qualitative relationships between DBC and bulk DOM imply that the transfer mechanism from soils to streams of soot-derived polycondensed DBC is linked with that of higher plant-derived, high-molecular-weight aromatic DOM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)