•Early vascular development involves proliferation, patterning and fate commitment.•A LHW-TMO5 bHLH complex plays a central role in early vascular development.•Regulation of auxin and cytokinin ...activities is tightly linked with LHW-TMO5.•Negative feedback loop regulates the output levels of LHW-TMO5.
The vascular system spreads throughout the plant body. This highly organized network contains several types of cells. Vascular cell development is initiated during embryogenesis, and then vascular cells proliferate, form a vascular pattern, and commit to specific cell fates. Recent molecular genetics and modeling approaches have increased our understanding of the molecular mechanisms underlying early vascular development. Early events during vascular development are tightly linked and controlled by transcriptional complexes consisting of LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS5 (TMO5) families. The role of LHW-TMO5 is tightly coupled with biosynthesis and/or signaling of phytohormones such as auxin and cytokinin. In this review, we discuss the regulatory network mediated by LHW-TMO5 during early vascular development.
•Specific modes of metabolism play important roles in hematopoietic stem cell (HSC) self-renewal.•Heterogeneity and technical challenges have prevented the elucidation of HSC behavior.•Recent ...advances have highlighted mitochondrial quality control as a key HSC fate factor.•A deeper understanding of HSC fate via metabolic control has clinical implications.
Hematopoietic stem cells maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions and this damage may eventually compromise the cells’ self-renewal capacity. Hematopoietic stem cell divisions result in either self-renewal or differentiation, with the balance between the two affecting hematopoietic homeostasis directly; however, the heterogeneity of available hematopoietic stem cell-enriched fractions, together with the technical challenges of observing hematopoietic stem cell behavior, has long hindered the analysis of individual hematopoietic stem cells and prevented the elucidation of this process. Recent advances in genetic models, metabolomics analyses, and single-cell approaches have revealed the contributions made to hematopoietic stem cell self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality control as a key factor in the equilibrium of hematopoietic stem cells. A deeper understanding of precisely how specific modes of metabolism control hematopoietic stem cells fate at the single-cell level is therefore not only of great biological interest, but will also have clear clinical implications for the development of therapies for hematological diseases.
Introduction
Phosphate binders (PBs) account for a large proportion of the daily pill burden in hemodialysis patients. However, patients do not take them all at once but at several dosing timings.
...Methods
We analyzed the dosing timings of all 322 types of oral drugs prescribed to 533 hemodialysis patients.
Results
The median daily dosing frequency for all drugs was 6 (4–7) times/day/patient. Patients prescribed PBs had a markedly higher daily dosing frequency than those not taking PBs (7 5–8 times/day/patient vs. 4 3–5 times/day/patient, respectively p < 0.001). In addition, the ratio of the number of PB pills to other drugs varied greatly at each dosing timing. Furthermore, it was simulated that the daily dosing frequency could be reduced by approximately two times/day/patient by combining the dosing timings of PBs.
Conclusion
Changing PB dosing timings can reduce the daily dosing frequency, which may lead to improved medication adherence.
Abstract
Coronary artery calcification (CAC) is associated with cardiovascular disease (CVD). CAC might contain calcium oxalate, and a high serum oxalate (S
Ox
) concentration is associated with ...cardiovascular mortality in dialysis patients. We assessed the associations between S
Ox
and CAC or CVD events in Japanese hemodialysis patients. This cross-sectional and retrospective cohort study was done in 2011. Seventy-seven hemodialysis patients’ Agatston CAC score was measured, and serum samples were collected. S
Ox
concentrations were measured in 2021 by using frozen samples. Also, new-onset CVD events in 2011–2021 were retrospectively recorded. The association between S
Ox
concentration and CAC score ≥ 1000, and new-onset CVD events were examined. Median S
Ox
concentration and CAC score were 266.9 (229.5–318.5) µmol/L and 912.5 (123.7–2944), respectively. CAC score ≥ 1000 was associated with S
Ox
adjusted odds ratio (OR) 1.01, 95% confidence interval (CI), 1.00–1.02. The number of new-onset CVD events was significantly higher in patients with S
Ox
≥ median value hazard ratio (HR) 2.71, 95% CI 1.26–6.16. By Cox proportional hazard models, new-onset CVD events was associated with S
Ox
≥ median value (adjusted HR 2.10, 95% CI 0.90–4.91). S
Ox
was associated with CAC score ≥ 1000 and new-onset CVD events in Japanese hemodialysis patients.
The analysis of intraocular pressure by age using a mega database showed a consistent age-related intraocular pressure decrease.
To clarify the association between age and intraocular pressure (IOP), ...the IOP value by age was assessed using a large IOP database.
This cross-sectional study was conducted among 103 health checkup institutions registered to the Japan Society of Ningen Dock, and included participants who underwent annual health checkups between April 2014 and March 2015. The inclusion criteria were as follows: complete data for IOP in eyes, body mass index, waist circumference, blood pressure, hemoglobin A1c, and a self-administered health questionnaire. A total of 655,818 participants were enrolled. The mean age was 51.5±10.5 years (range, 20-96 y), and 40.1% were women. IOP was measured using a noncontact tonometer. Multiple linear regression analysis was conducted to explore factors associated with IOP, including age, and analyses stratified by age group: <40, 40-69, and ≥70 years.
A consistent negative association between IOP and age β=-0.353 (95% confidence interval: -0.360--0.346) was observed. In the age groups of <40 and ≥70 years, the age-related IOP decline was more pronounced β=-0.502 (95% CI: -0.566 to -0.439); β=-0.674 (95% CI: -0.753 to -0.595), with it being 14.21±2.95 and 11.18±2.52 mm Hg in the 20-24 and 90-96 year age groups, respectively. The middle-aged (aged 40-69 y) population showed gradual decline β=-0.313 (95% CI: -0.323 to -0.303).
Age was strongly and negatively associated with IOP. The magnitude of IOP decline across lifespans was ∼3 mmHg. Age-related decreases in IOP were nonlinear and phasic.
In order to design a work environment that improves office workers’ intellectual productivity, the authors have focused on airflow, which is a key factor in thermal environments. An airflow control ...method that improves the degree of concentration is proposed, and its effectiveness is evaluated objectively and quantitatively by evaluative experiments. The designed airflow environment is composed of two airflow components: a stimulative airflow and a mild airflow. In this experiment, cognitive tasks are given to participants. The concentration time ratio (CTR), which is a quantitative and objective evaluation index of the degree of concentration, is measured. The results show that the average CTR under the proposed airflow condition is 61.1%, while that under the no airflow condition is 54.6%. The proposed airflow control shows a significant improvement in CTR, with an increase of 6.5% (p < 0.001). Consequently, our findings suggest that intellectual work can be performed better in an environment that fosters a high concentration time ratio.
•Indoor environmental control that improves concentration during intellectual work.•Objective/quantitative index of concentration to evaluate intellectual productivity.•Proposing concentration-improving airflow composed of two types of control.•Effectiveness of the proposed airflow control validated by subject experiment.•Degree of concentration improved by 6.5% under the airflow control (p < 0.001).
Spatiotemporal control of cell division in the meristem is vital for plant growth. In the stele of the root apical meristem (RAM), procambial cells divide periclinally to increase the number of ...vascular cell files. Class III homeodomain leucine zipper (HD-ZIP III) proteins are key transcriptional regulators of RAM development and suppress the periclinal division of vascular cells in the stele; however, the mechanism underlying the regulation of vascular cell division by HD-ZIP III transcription factors (TFs) remains largely unknown. Here, we performed transcriptome analysis to identify downstream genes of HD-ZIP III and found that HD-ZIP III TFs positively regulate brassinosteroid biosynthesis-related genes, such as
(
), in vascular cells. Introduction of
in a quadruple loss-of-function mutant of
genes partly rescued the phenotype in terms of the vascular defect in the RAM. Treatment of a quadruple loss-of-function mutant, a gain-of-function mutant of
, and the wild type with brassinosteroid and a brassinosteroid synthesis inhibitor also indicated that HD-ZIP III TFs act together to suppress vascular cell division by increasing brassinosteroid levels. Furthermore, brassinosteroid application suppressed the cytokinin response in vascular cells. Together, our findings suggest that the suppression of vascular cell division by HD-ZIP III TFs is caused, at least in part, by the increase in brassinosteroid levels through the transcriptional activation of brassinosteroid biosynthesis genes in the vascular cells of the RAM. This elevated brassinosteroid level suppresses cytokinin response in vascular cells, inhibiting vascular cell division in the RAM.
Fibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease. In this post hoc analysis of the ASTRIO study (UMIN000019176), we investigated the ...relationship between FGF23 and α-klotho during treatment with an iron-based phosphate binder, ferric citrate hydrate (FC), compared with non-iron-based phosphate binders in hemodialysis (HD) patients. We examined the effect of iron absorption by FC on the relationship between FGF23 and α-klotho. There have been few clinical studies evaluating these biomarkers simultaneously in HD patients.
The ASTRIO study was a 24-week, randomized, open-label, multicenter trial. HD patients taking non-iron-based phosphate binder(s) were randomized at a 1:1 ratio to continue other binder(s) (control group) or switch to FC (FC group). Serum phosphate (P) and hemoglobin (Hb) were maintained within 3.5-6.0 mg/dL and 10-12 g/dL, respectively. Plasma levels of intact FGF23 (i-FGF23), C-terminal FGF23 (c-FGF23), and α-klotho were measured, as were iron-related parameters. Association analyses of FGF23 and α-klotho were conducted.
Patients were randomized to FC (n = 48) and control (n = 45) groups. Serum ferritin significantly increased from baseline to end-of-treatment (EOT) in the FC group, compared with the control group (adjusted mean difference 95% confidence interval: 79.5 44.7, 114.4 ng/mL; p < 0.001). The mean change from baseline to EOT in c-FGF23 was significantly different between the FC and control groups (mean ± standard deviation (SD): - 0.2 ± 0.8 log
pg/mL vs. 0.2 ± 0.8 log
pg/mL, respectively; p = 0.04). The mean change from baseline to EOT in i-FGF23 and α-klotho were not significantly different between the FC and control groups (mean ± SD: - 0.1 ± 0.8 log
pg/mL vs. 0.1 ± 0.9 log
pg/mL; p = 0.33, and 2.0 ± 91.5 pg/mL vs. - 8.9 ± 145.3; p = 0.58, respectively). However, both forms of FGF23 and α-klotho were not significantly associated with each other in both groups.
Iron absorbed via FC administration in HD patients did not influence the correlation relationship between plasma levels of FGF23 and α-klotho under the condition of serum P and Hb were maintained.
ASTRIO study ( UMIN000019176 , registered at UMIN Clinical Trials Registry on October 1, 2015).
We compared quantity and structures of food-derived gelatin hydrolysates in human blood from three sources of type I collagen in a single blind crossover study. Five healthy male volunteers ingested ...type I gelatin hydrolysates from fish scale, fish skin, or porcine skin after 12 h of fasting. Amounts of free form Hyp and Hyp-containing peptide were measured over a 24-h period. Hyp-containing peptides comprised approximately 30% of all detected Hyp. The total area under the concentration−time curve of the fish scale group was significantly higher than that of the porcine skin group. Pro-Hyp was a major constituent of Hyp-containing peptides. Ala-Hyp, Leu-Hyp, Ile-Hyp, Phe-Hyp, and Pro-Hyp-Gly were detected only with fish scale or fish skin gelatin hydrolysates. Ala-Hyp-Gly and Ser-Hyp-Gly were detected only with fish scale gelatin hydrolysate. The quantity and structure of Hyp-containing peptides in human blood after oral administration of gelatin hydrolysate depends on the gelatin source. Keywords: Collagen; gelatin; gelatin hydrolysate; peptide; absorption
Abstract Background End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing ...mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 sST2, galectin-3 Gal-3), and uremic toxicity (indoxyl sulfate IS). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients, and have incremental prognostic value over the clinical score and NT-proBNP level. Methods A total of 423 hemodialysis patients were prospectively followed for primary (all-cause death) and secondary endpoints (a composite of all-cause death or cerebro-cardiovascular events). Results During a mean follow-up of 2.1 ± 0.4 years, there were 48 all-cause deaths and 78 composite outcomes. sST2, Gal-3, and NT-proBNP were associated with all-cause deaths but IS was not in both log-rank test and receiver operating characteristic analysis. Both sST2 and Gal-3 had independent and incremental prognostic value for both outcomes over the AROii score and NT-proBNP. Although adding sST2 did not reclassify over the model based AROii score and NT-proBNP for all-cause death, further addition of Gal-3 did. Subgroup analyses of patients with left ventricular ejection fraction measurement (n=301) corroborated these results, where the two biomarkers remained independent and incremental for both all-cause death and composite outcome after adjusting for the risk score and the ejection fraction. Conclusions Both sST2 and Gal-3 had independent and incremental prognostic values over NT-proBNP and an established risk score in patients with hemodialysis. Assessment of sST2 and Gal-3 further enhances risk stratification.
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