Elevated Phosphate Research Articles

Sex-dependent interplay of phosphate and inflammation on muscle strength irrespective of muscle mass in middle-aged and older adults

BackgroundElevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations. MethodsThe study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship. ResultsThe study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone. ConclusionsThis study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

Improvement of Bone Metabolism in Prepubertal Girls with Turner Syndrome Following Long-term Pegylated Growth Hormone Treatment.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis

Abstract Disclosure: T.G. de Souza: None. T.J. Weber: None. Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC. Presentation: 6/1/2024

Unravelling the Seasonal Dynamics of Limnological Parameters and Assessment of Ecological Health: A Case Study of Lingadheeranahalli Lake in Bangalore North, Karnataka, India

ABSTRACT: The present study investigates the seasonal dynamics of limnological variables and the developmental response of D. rerio in the wetland ecosystem of Lingadheeranahalli in the northern clutches of Bangalore in Karnataka. Once a vital water source for agriculture and replenishing groundwater, the lake faces degradation due to anthropogenic activities and the need for more awareness. A yearlong analysis was conducted with five sampling seasons and three sampling stations identified within the wetland. Parameters viz. physical, chemical, and biological were analyzed following American Public Health Association (APHA) guidelines. Somite development was studied using embryos while the heart rate was counted during the torpedo stage of D. rerio. The results of this comprehensive study revealed unique and significant seasonal variations over limnological parameters, providing novel insights into the dynamics of the wetland ecosystem. pH values are slightly acidic and influenced by precipitation and terrestrial vegetation. Turbidity spiked during winter due to colloidal dispersions, while conductivity peaked in spring due to sewage disposal. Reduced dissolved oxygen, high biochemical and chemical oxygen demand indicated organic pollution and microbial activity, particularly affecting the inlet station. Elevated phosphate and nitrate levels in spring indicated eutrophication potential. The influence of rains and mineral leaching during monsoons affected parameters such as alkalinity, total dissolved solids, total hardness, and Magnesium. Analysis of D. rerio demonstrated delayed development and decreased heart rates in the inlet and deposit stations, indicative of potent stressors in the wetland ecosystem. All-inclusive Lingadheeranahalli Lake exhibited poor water quality, focusing on the need for adaptive management strategies to mitigate pollution and safeguard wetland ecosystems. Continued wetland research gives more insights into water quality and seasonal dynamics, paving the way for its conservation.

Enhanced phosphate removal from aqueous environments using three-dimensional La-doped carboxylic carbon nanotubes/alginate: Performance and mechanisms

The excessive amounts of phosphorus (P) discharged and usage have caused eutrophication and algal blooms, which seriously jeopardize the environment even the human health. In this study, carbon nanotubes (CNTs) served as carriers to develop a lanthanum-based sodium alginate hydrogel (La-CNT-COOH/SA) aimed at efficiently removing phosphate from wastewater. Characterization results confirmed successful deposition of La(OH)3 nanoparticles onto CNT-COOH. The optimal adsorption efficiency of La-CNT-COOH/SA hydrogels occurred at pH 4, with a maximum adsorption capacity of 54.4 mg/g under an initial phosphate concentration of 60 mg/L. Batch experiments demonstrated that La-CNT-COOH/SA performed well across a favorable pH range and exhibited high tolerance to common coexisting ions during phosphate adsorption. Adsorption isotherms indicated a dominance of both physical and chemical mechanisms in phosphate removal by La-CNT-COOH/SA. At elevated phosphate concentrations, the adsorption process followed quasi-second-order kinetics, primarily driven by chemical adsorption. Multi-instrument characterization emphasized that the substantial loading of La(OH)3 on CNT-COOH significantly contributed to adsorption, alongside crosslinked lanthanum ions on sodium alginate and abundant hydroxyl groups. Mechanisms of adsorption by La-CNT-COOH/SA encompassed electrostatic interactions, surface precipitation, and in-sphere complexation (La-O-P). These findings on fabrication, properties, and adsorption mechanisms of the phosphate-removal hydrogel lay a theoretical foundation for applying biomass-based materials in large-scale remediation practices.

Infiltration of secondary treated wastewater into an oxic aquifer: Hydrochemical insights from a large-scale sand tank experiment

To mitigate groundwater level decline, managed aquifer recharge (MAR) with secondary treated wastewater (STWW) is increasingly considered and implemented. However, the effectiveness and potential risks of such systems need evaluation prior to implementation. In this study, we present a large-scale sand tank experiment to analyse processes related to the infiltration of real STWW through the vadose zone and subsequent mixing with oxic native groundwater. The varying composition of STWW from 15 infiltration cycles over six months of operation and the retention times were the main drivers of the observed processes, which were characterized by a wide range of analytical techniques such as in situ high-resolution oxidation–reduction potential (ORP) measurements, closed mass balances of solutes, characterization of dissolved organic carbon (DOC), stable nitrate isotopes analysis, as well as numerical flow and transport modelling. Depending on the composition and infiltration rates of the STWW, both nitrification and denitrification could be observed, even simultaneously at different locations in the tank. Furthermore, due to the variability of the real STWW we observed enhanced arsenic mobilisation during times of elevated phosphate concentrations of the infiltrating STWW. Additionally, uranium was mobilised in our experimental system via carbonate mineral dissolution caused by the infiltrating STWW which was undersaturated of calcite for all infiltration cycles. Overall, our results showed the importance of conducting studies with waters of complex matrix, such as real STWW, and considering mixing with groundwater to assess the full range of possible processes encountered at MAR field sites.

Deficiency of metabolic regulator PKM2 activates the pentose phosphate pathway and generates TCF1+ progenitor CD8+ T cells to improve immunotherapy.

TCF1high progenitor CD8+ T cells mediate the efficacy of immunotherapy; however, the mechanisms that govern their generation and maintenance are poorly understood. Here, we show that targeting glycolysis through deletion of pyruvate kinase muscle 2 (PKM2) results in elevated pentose phosphate pathway (PPP) activity, leading to enrichment of a TCF1high progenitor-exhausted-like phenotype and increased responsiveness to PD-1 blockade in vivo. PKM2KO CD8+ T cells showed reduced glycolytic flux, accumulation of glycolytic intermediates and PPP metabolites and increased PPP cycling as determined by 1,2-13C glucose carbon tracing. Small molecule agonism of the PPP without acute glycolytic impairment skewed CD8+ T cells toward a TCF1high population, generated a unique transcriptional landscape and adoptive transfer of agonist-treated CD8+ T cells enhanced tumor control in mice in combination with PD-1 blockade and promoted tumor killing in patient-derived tumor organoids. Our study demonstrates a new metabolic reprogramming that contributes to a progenitor-like T cell state promoting immunotherapy efficacy.

Eiken syndrome with parathyroid hormone resistance due to a novel parathyroid hormone receptor type 1 mutation: clinical features and functional analysis.

We report two patients of east African ancestry with the same novel homozygous variant in the parathyroid hormone receptor type 1 (PTH1R). Both patients shared skeletal features including brachydactyly, extensive metacarpal pseudoepiphyses, elongated cone-shaped epiphyses, ischiopubic hypoplasia, deficient sacral ossification, suggestive of Eiken syndrome. Strikingly, both patients exhibited clinically manifest parathyroid hormone (PTH) resistance with hypocalcaemia and elevated serum phosphate levels. These laboratory and clinical abnormalities initially suggested pseudohypoparathyroidism, which is typically associated with GNAS abnormalities. In both patients, however, a homozygous novel PTH1R variant was identified (c.710T > A; p.IIe237Asn, p.I237N) that is located in the second transmembrane helical domain. Previously, others have reported a patient with a nearby PTH1R mutation (D241E) who presented with similar clinical features, e.g. delayed bone mineralization as well as clinical PTH resistance. Functional analysis of the effects of both novel PTH1R variants (I237N- and D241E-PTH1R) in HEK293 reporter cells transfected with plasmid DNA encoding the wild-type or mutant PTH1Rs demonstrated increased basal cAMP signalling for both variants, with relative blunting of responses to both PTH and PTH-related peptide (PTHrP) ligands. The clinical presentation of PTH resistance and delayed bone mineralization combined with the functional properties of the mutant PTH1Rs suggest that this form of Eiken syndrome results from alterations in PTH1R-mediated signalling in response to both canonical ligands, PTH and PTHrP.

Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3-/-). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3-/-, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

Higher phosphate concentrations as in aqueous humor of diabetic patients increase intraocular lens calcification

BackgroundClinical evidence suggests an association between phosphate concentrations in aqueous humor and the risk of intraocular lens (IOL) calcification. To test this hypothesis the influence of different phosphate concentrations on IOL calcification was evaluated in an in vitro electrophoresis model.Methods20 IOLs of two hydrophilic IOL models (CT Spheris 204, Zeiss; Lentis L-313, Oculentis) and one hydrophobic control IOL model (Clareon CNA0T0, Alcon) were exposed to physiologic and elevated phosphate concentrations, similar to diabetic aqueous humor. IOL calcification was analyzed by alizarin red staining, von Kossa staining, scanning electron microscopy, energy dispersive x-ray spectroscopy and transmission electron microscopy with electron diffraction.ResultsHigher phosphate concentrations were associated with IOL calcification. Analyses of IOL surfaces and cross-sections documented calcification in no CT Spheris and 4 Lentis IOLs following exposure to 10 mM Na2HPO4, compared with 7 and 11 positive analyses following exposure to 14 mM Na2HPO4, respectively. Furthermore, a clear association between IOL calcification and the duration of electrophoresis was demonstrated, confirming increased phosphate concentrations and duration of exposure as risk factors of IOL calcification.ConclusionsFindings suggest that higher phosphate concentrations in aqueous humor, as seen in diabetic patients, contribute to an increased IOL calcification risk, potentially explaining clinical observations showing an increased risk of IOL calcification in patients with diabetes.

Cardiac Fibroblasts Produce Fibroblast Growth Factor 23 in Response to Hyperphosphatemia

Chronic Kidney Disease (CKD) is accompanied by pathologic cardiac remodeling, including cardiac hypertrophy and fibrosis. The decline in renal function results in elevations of serum concentrations of phosphate (hyperphosphatemia) and of the bone-derived hormone Fibroblast Growth Factor (FGF) 23. Clinical studies have shown that hyperphosphatemia and high circulating levels of FGF23 are associated with cardiovascular mortality in CKD. We previously found that FGF23 can directly target cardiac myocytes via FGF Receptor (FGFR) 4 and induce cardiac hypertrophy in rodents. Furthermore, decreasing serum FGF23 levels or pharmacological blockade of FGFR4 in rodent models of hyperphosphatemia and CKD reduces cardiac hypertrophy, but not cardiac fibrosis. To directly determine whether cardiac fibroblasts are resistant to FGF23 elevations, we isolated cardiac fibroblasts from adult mice and treated them with recombinant FGF23 protein, which did not induce proliferation, pro-fibrotic gene programs or differentiation into myofibroblasts. Similarly, cardiac fibroblasts isolated from mice receiving a high-phosphate diet did also not respond to FGF23, indicating that hyperphosphatemia does not prime cardiac fibroblasts for FGF23 responsiveness. However, cardiac fibroblasts derived from mice on high-phosphate diet produced and secreted FGF23. Our study suggests that cardiac fibroblasts are not a target but a source of FGF23 and that FGF23/FGFR4 signaling is a driver of cardiac hypertrophy but not fibrosis. Elevated phosphate appears to not only induce FGF23 production in bone but also in cardiac fibroblasts which in a paracrine manner might contribute to cardiac hypertrophy in scenarios of hyperphosphatemia, such as CKD.

Snapshot of a Paleoarchean seafloor: Evidence from 3.43-3.35 Ga Strelley Pool chert-pebble conglomerate for deposition, silicification, and erosion of hydrothermal greenalite-apatite precipitates

Some of the oldest, well-preserved exhalative sedimentary rocks (ferruginous cherts and jaspilites) occur in volcanic-dominated Paleoarchean sequences in the northern Pilbara Craton, Australia. Jaspilites contain fine-grained hematite particles that have been interpreted to have formed following seawater oxidation of vent-derived Fe2+(aq) by photoautotrophs. However, recent studies suggest that most of the iron in the jaspilites was originally deposited as Fe(II)-rich silicates such as greenalite, sparking renewed debate about how iron was precipitated in the early oceans. Here we show that rounded clasts of dusty ferruginous chert in basal conglomerates of the 3.43–3.35 Ga Strelley Pool Formation, North Pole Dome, Pilbara Craton, Australia, contain abundant nanoparticles of greenalite and apatite that are texturally, mineralogically and chemically near-identical to occurrences in Neoarchean banded iron formations in the Hamersley Group, Australia. Hematite where present occurs in trace amounts and its distribution along the edges of clasts implies that at least some of the hematite formed during weathering. The greenalite-rich clasts display a pronounced positive shale-normalized Eu anomaly, small positive Y anomaly and lack a positive La anomaly, features typical of Paleoarchean exhalites. The co-occurrence of greenalite- and apatite-rich chert-pebbles with clasts of hydrothermal black chert and silicified felsic volcaniclastic sedimentary rocks points to a volcanically active provenance with vigorous hydrothermal activity, consistent with derivation from the underlying 3.43 Ga Panorama Formation. We argue that the greenalite and apatite nanoparticles precipitated during mixing between hydrothermal vent fluids and anoxic seawater and were silicified on the seafloor. The round to oval shape of the chert clasts indicates that the silica cement had recrystallized prior to erosion, consistent with the presence of polygonal shrinkage structures in the dusty chert clasts. Our findings imply that greenalite, contrary to recent suggestions, not only formed in Paleoarchean seawater, but was also stable during deposition, diagenesis, and resedimentation. The precipitation and non-dissolution of apatite nanoparticles in Paleoarchean seawater points to elevated phosphate concentrations, whereas the absence of primary hematite is consistent with models advocating a role for abiotic iron deposition during the Archean.

Nutrient accumulations in high-saline bottom waters in the eutrophic East China Sea inner shelf

Despite decades of mitigation efforts, eutrophication-induced algal blooms and hypoxia have not significantly decreased globally, possibly due to the legacy effects of eutrophication. The legacy effect has been more explored in inland waters and enclosed estuaries than in open coastal waters. Here, we reanalyzed cruise data from the East China Sea inner shelf to explore the effect of eutrophication on nutrient accumulations in high-saline bottom waters. Our dataset showed elevated nitrate (12.75 ± 6.51 μmol L−1) and phosphate (0.85 ± 0.26 μmol L−1) in high-salinity (salinity>34, temperature < 23 °C) bottom waters during the summer of 2006 to 2013. They were higher than those typically observed in the Taiwan Warm Current Bottom Water by approximately 5.45 ± 6.51, and 0.29 ± 0.26 μmol L−1, respectively. Significant correlations of nitrate with apparent oxygen utilization (AOU) and elevated AOU suggested that organic matter decomposition contributed to increased nitrate in bottom waters under eutrophication conditions. Based on an end-member mixing estimation, we found that the organic matter decomposition accounted for 28% to 37% of the nutrient concentrations in the bottom waters, with a standard deviation of 20%. Results from our mass-balance model indicated that 40–74% of regenerated nutrients are flushed out of the model box set within 95% equilibrium time due to the advection of offshore waters, assuming a residence time of 46.0 to 13.9 days. Based on cruise results in June and August 2009, the net accumulation rates of nitrate, phosphate, and AOU in the Taiwan Warm Current Bottom Water were estimated to be 0.046, 0.0036, and 0.44 μmol L−1 d−1, respectively. Such nutrient accumulations in the water column and the residual nutrients in sediment are crucial legacy nutrients, potentially triggering algal blooms. Conversely, the flushing effect suggests a significant transport of nutrients and other chemical elements to the offshore and open ocean.

Chronic Kidney Disease-associated Lung Injury Is Mediated by Phosphate-induced MAPK/AKT Signaling.

Chronic kidney disease (CKD) is associated with systemic phosphate elevations, called hyperphosphatemia. Translational studies have shown that hyperphosphatemia contributes to CKD-associated inflammation and injury in various tissues, including the kidney, heart, liver, and parathyroid gland. Mechanisms underlying pathologic actions of elevated phosphate on cells are not well understood but seem to involve uptake of phosphate through sodium-phosphate cotransporters and phosphate-induced signaling via fibroblast growth factor receptor (FGFR) 1. Clinical studies indicate CKD patients are more likely to develop inflammatory and restrictive lung diseases, such as fibrotic interstitial lung diseases, and here we aimed to determine whether hyperphosphatemia can cause lung injury. We found that a mouse model of CKD and hyperphosphatemia, induced by an adenine-rich diet, develops lung fibrosis and inflammation. Elevation of systemic phosphate levels by administration of a high-phosphate diet in a mouse model of primary lung inflammation and fibrosis, induced by bleomycin, exacerbated lung injury in the absence of kidney damage. Our in vitro studies identified increases of proinflammatory cytokines in human lung fibroblasts exposed to phosphate elevations. Phosphate activated extracellular signal related kinase (ERK) 1/2 and protein kinase B (PKB/AKT) signaling, and pharmacological inhibition of ERK, AKT, FGFR1, or sodium-phosphate cotransporters prevented phosphate-induced proinflammatory cytokine upregulation. Additionally, inhibition of FGFR1 or sodium-phosphate cotransporters decreased the phosphate-induced activation of ERK and AKT. Our study suggests that phosphate can directly target lung fibroblasts and induce an inflammatory response and that hyperphosphatemia in CKD and non-CKD models contributes to lung injury. Phosphate-lowering strategies might protect from CKD-associated lung injury.

Mobile Phosphorus Presence of Typical Chernozems on Fertiliser System

Abstract Due to the systematic utilisation of substantial amounts of phosphorus fertilisers on agricultural crops in crop rotation, the amount of available phosphate compounds increases in the soil. It ensures the maximum increase in crop yields. The study of the phosphate level in chernozem soils in various agrocenoses is really up-to-date. The gist of our research was to determine the specifics of providing mobile phosphorus in typical chernozem in field crop rotation, especially in sunflower, varying according to fertilisation systems in the forest-steppe zone of Ukraine. The assessment of mobile phosphorus content was conducted using the Chirikov method, which involves extracting mobile phosphorus compounds from the soil using a solution containing acetic acid (CH3COOH) at a concentration of 0.5 mol dm−3, with a soil–to–solution ratio of 1:25. Phosphorus was determined with the spectrophotocolorimetric method, which is based on the colour intensity of the phosphorus-molybdenum complex. Our investigations showed that the typical low-humus chernozems have considerable reservoirs of potentially exploitable phosphorus for plant nourishment. We established that the mineral and organic-mineral fertilisation system leads to a greater use of mobile phosphorus with agricultural crops of crop rotation resulting in the formation of elevated phosphate content in the chernozem soil. By the end of the second rotation, the organic-mineral fertilisation system variant displayed the greatest concentration of mobile phosphorus within the 0–25 cm soil depth, marking a surge of 15.6 mg kg−1 compared to the unfertilised variant. In the period of sunflower germination, the content of mobile phosphates increased in the soil layers at depths of 0–25 cm and 25–50 cm in the variant of the mineral fertilisation system on 17.6 and 22.2 mg kg−1 of soil compared to the alternative without the fertiliser. In the sunflower’s ripening period, the mobile phosphorus concentration in the soil at 0–25 cm depth increased significantly in the variant of organic-mineral fertilisation system by 12.0 mg kg−1 and mineral fertilisation by 14.7 mg kg−1 of soil if compared with the variant lacking the fertiliser. In the variant of the mineral fertilisation system, the amount of mobile phosphorus increased in the 0–30 cm soil depth by 18.7 mg kg−1 of soil in two crop rotations compared to the beginning of the first crop rotation.

Water Quality Identification and Analysis of Saguling Reservoir, West Bandung Regency

The Saguling Reservoir in West Bandung Regency is crucial for local water supply and biodiversity. However, water quality has significantly declined due to human activities, environmental changes, and poor waste management. This degradation jeopardizes the reservoir's clean water supply and the ecological health of surrounding communities. This research used the STORET (Storage and Retrieval) method to assess water quality through purposive sampling in the most affected zones, analyzing physical, chemical, and biological parameters at multiple depths. Key indicators, such as dissolved oxygen, nutrient concentrations, and heavy metal presence, were measured. Results show severe water quality deterioration, especially in deeper sections with less sunlight and aeration. Elevated nitrate and phosphate levels, mainly from agricultural runoff and residential waste, exceeded environmental safety standards. Toxic heavy metals like lead and mercury were also detected, posing serious risks to aquatic life and human health. The study highlights that deeper water zones are critically impacted by pollutants, stressing the need for better regulatory frameworks and waste management. Immediate strategic interventions are crucial to restore and protect the Saguling Reservoir's water quality for future generations.

Serum phosphate levels at diagnosis predict long-term risk for hypopituitarism in patients with acromegaly.

Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated. This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conductingcorrelation analysis and multivariable logistic regression. Sixty-one patients were followed for 4.5years (range 1-21). Patients with hyperphosphatemia (> 4.5mg/dl) at baseline had larger adenomas (15.0mm [8.0, 47.0] vs. 10.0mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0nmol/l [27.6, 516.0] vs. 294.0nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01). Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

Zaxinone Synthase overexpression modulates rice physiology and metabolism, enhancing nutrient uptake, growth and productivity.

The rice Zaxinone Synthase (ZAS) gene encodes a carotenoid cleavage dioxygenase (CCD) that forms the apocarotenoid growth regulator zaxinone in vitro. Here, we generated and characterized constitutive ZAS-overexpressing rice lines, to better understand ZAS role in determining zaxinone content and regulating growth and architecture. ZAS overexpression enhanced endogenous zaxinone level, promoted root growth and increased the number of productive tillers, leading to about 30% higher grain yield per plant. Hormone analysis revealed a decrease in strigolactone (SL) content, which we confirmed by rescuing the high-tillering phenotype through application of a SL analogue. Metabolomics analysis revealed that ZAS overexpressing plants accumulate higher amounts of monosaccharide sugars, in line with transcriptome analysis. Moreover, transgenic plants showed higher carbon (C) assimilation rate and elevated root phosphate, nitrate and sulphate level, enhancing the tolerance towards low phosphate (Pi). Our study confirms ZAS as an important determinant of rice growth and architecture and shows that ZAS regulates hormone homoeostasis and a combination of physiological processes to promote growth and grain yield, which makes this gene an excellent candidate for sustainable crop improvement.

Effect of Phosphate on the Molecular Properties, Interactions, and Assembly of Engineered Spider Silk Proteins.

Phosphate plays a vital role in spider silk spinning and has been utilized in numerous artificial silk spinning attempts to replicate the remarkable mechanical properties of natural silk fiber. Its application in artificial processes has, however, yielded varying outcomes. It is thus necessary to investigate the origins and mechanisms behind these differences. By using recombinant silk protein SC-ADF3 derived from the garden spider Araneus diadematus, here, we describe its conformational changes under various conditions, elucidating the effect of phosphate on SC-ADF3 silk protein properties and interactions. Our results demonstrate that elevated phosphate levels induce the irreversible conformational conversion of SC-ADF3 from random coils to β-sheet structures, leading to decreased protein solubility over time. Furthermore, exposure of SC-ADF3 to phosphate stiffens already formed structures and reduces the ability to form new interactions. Our findings offer insights into the underlying mechanism through which phosphate-induced β-sheet structures in ADF3-related silk proteins impede fiber formation in the subsequent phases. From a broader perspective, our studies emphasize the significance of silk protein conformation for functional material formation, highlighting that the formation of β-sheet structures at the initial stages of protein assembly will affect the outcome of material forming processes.

RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.