Organic Accumulation Research Articles

Bismuth release from endodontic materials: in vivo analysis using Wistar rats

Calcium silicate-based materials are used to block the communication between the root canal and the periodontal ligament space. This brings the materials into contact with tissues and the potential for local and systemic elemental release and movement. The aim of the study was to evaluate the elemental release of bismuth from ProRoot MTA in contact with connective tissues after 30 and 180 days as well as any accumulation in peripheral organs using an animal model. Tricalcium silicate and hydroxyapatite containing 20% bismuth oxide (HAp-Bi) were used as controls. The null hypothesis was that bismuth migrates from tricalcium silicate-based materials when associated with silicon. The materials were examined using scanning electron microscopy, energy dispersive spectroscopy (SEM/EDS) and X-ray diffraction prior to implantation as well as using SEM/EDS, micro X-ray fluorescence and Raman spectroscopy after implantation to assess elemental presence in surrounding tissues. Histological analysis was used to evaluate the changes in tissue architecture and inductively coupled plasma mass spectrometry (ICP-MS) was used to investigate the elemental deposition. For the systemic investigation, routine blood analysis was performed and organs were obtained to evaluate the presence of bismuth and silicon using ICP-MS after acid digestion. In the histological analysis of the implantation sites, macrophages and multinucleated giant cells could be observed after 30 days which after 180 days became a chronic infiltrate; although, no major differences were identified in red and white blood cell analyses and biochemical tests. Implantation altered the materials as observed in the Raman analysis and bismuth was detected both locally and within kidney samples after both periods of analysis, indicating the potential for accumulation of bismuth in this organ. Smaller amounts of bismuth than observed in the kidney were also detected in blood, liver and brain for the ProRoot MTA and HAp-Bi after 180 days. Bismuth was released from the ProRoot MTA locally and was detected systemically and in samples without silicon; thus, the null hypothesis was rejected. The bismuth release demonstrated that this element accumulated both locally and systemically, mainly in the kidneys in comparison with brain and liver regardless of the material base.

Skin autofluorescence as an indicator of advanced glycation end-product accumulation in the prognosis of age-related cardiovascular disease: literature review

Advanced glycation end products (AGEs) are represented by heterogeneous molecular structures and their accumulation in organs and tissues reflects the intensity of oxidative stress and glycemia. As a physiological process, aging is associated with AGE accumulation and changing the morphology and functions of the vascular wall. Accelerated AGE accumulation initiates inflammation, contributing to the development of cardiovascular diseases, such as arterial hypertension, coronary heart diseases, and atherosclerosis of peripheral arteries; conditions associated with high cardiovascular risks such as prediabetes, diabetes mellitus type 2, and chronic kidney diseases are also characterized by the accelerated AGEs accumulation. The ability of AGEs to fluorescence underlies noninvasively in blood serum, tissues, and skin using a well-proven technique of autofluorescence, which is little known to domestic specialists. This review presents the possibilities of autofluorescence to reflect arterial wall remodeling, which includes stiffness, vascular endothelial function, atherosclerotic plaque formation, and instability, using modern materials. The review emphasizes the evidence base regarding the ability of this method to predict mortality and cardiovascular events in a large population from low to high risk.

Palaeoenvironmental history of the Middle Pleistocene deposits at Gilson, Warwickshire, England: part of the High Speed Two railway route alignment

ABSTRACTThe investigation of a hillside at Gilson (Lat. 52.510341, Long. ‐1.718313), southwest of Coleshill, Warwickshire (within the High Speed Two railway ‘Delta Junction’ compound), England, has yielded evidence of sedimentation during a temperate stage. The site's stratigraphy starts with the aggregation of cold‐climate sand and gravels deposited during the Anglian Stage within the proto‐Tame and proto‐Blythe palaeovalleys. A warm‐climate period is recorded by the infill of organic material representing the second half of the Hoxnian interglacial Stage. Picea, Abies and Pinus dominate vegetation within a swamp‐like environment, before a Pinus forest develops in the upper part of the organic sequence. The following cold‐climate period saw incision and aggregation of the surrounding region throughout much of the Wolstonian and Devensian Stages, where much of the overlying silt, sand and gravel were reworked under intense periglacial conditions. Presented here is a geophysical examination of the shallow basin by ground‐penetrating radar undertaken to understand the spatial distribution and stratigraphical history of the basin. The deposits at Gilson provide a valuable stratigraphic marker in the glacial sequence of the English West Midlands and are correlated to similar deposits at neighbouring Quinton and Nechells. At these regional sites organic accumulation occurred for most of the temperate stage, infilling lake basins. These sequences indicate an environment dominated by pollen of Abies, Quercus, Ulmus and Corylus woodland vegetation. These assemblages differ markedly from those typically found in the last interglacial and confirm correlation to the Middle Pleistocene Hoxnian interglacial Stage (c. MIS 11c).

EE523 Analysis of Healthcare Resource Utilization and Costs in Patients with Glycogen Storage Disease Type Ia (GSDIA)

Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited glucose-6-phosphatase deficiency characterized by glycogen accumulation in organs and tissues. Despite best practices with dietary carbohydrate supplementation, patients experience serious complications and require frequent care. This retrospective cohort study quantified healthcare resource utilization (HRU) and management costs associated with GSDIa.

Absence of aluminium compromises root integrity, reduces leaf hydration and Rubisco performance in Qualea grandiflora, an Al-accumulating species.

Aluminium (Al) is toxic to most plants. Nevertheless, some species accumulate Al without showing toxicity symptoms. Previous studies have evidenced Al in chloroplasts of Al-accumulating species from the Cerrado vegetation in South America. We ask whether Al increases carbon assimilation through enhanced apparent efficiency of Rubisco. Seedlings of the Al-accumulator Qualea grandiflora (Vochysiaceae) were grown in nutrient solution with 0, 740, and 1480 μm Al. Growth parameters, relative leaf water content, Al concentration in organs, gas exchange and apparent carboxylation efficiency (measured from A/Ci curves) were evaluated for 60 days. Plants without Al showed no root growth, necrotic roots, low gas exchange rates, and decreased apparent carboxylation efficiency. Al-treated plants, however, showed new white roots and increased root biomass leading to higher leaf hydration, and apparent carboxylation efficiency was higher in these plants. Increased Al available in the nutrient solution increased Al accumulation in plant organs. Absence of Al compromised root integrity in Q. grandiflora, thus limiting leaf hydration. No positive direct effect of Al on Rubisco was evidenced in Al-treated plants.

68Ga]Ga-Ornibactin for Burkholderia cepacia complex Infection Imaging Using Positron Emission Tomography.

Bacteria from the Burkholderia cepacia complex are generally considered to be non-pathogenic to the healthy population. However, some of these species may cause serious nosocomial infections in immunocompromised patients; as such, it is essential to diagnose these infections rapidly so that adequate treatment can be initiated. We report here the use of a radiolabeled siderophore, ornibactin (ORNB), for positron emission tomography imaging. We successfully radiolabeled ORNB with gallium-68 with high radiochemical purity and proved that the resulting complex has optimal in vitro characteristics. In mice, the complex did not show excessive accumulation in organs and was excreted in the urine. We demonstrated that the [68Ga]Ga-ORNB complex accumulates at the site of Burkholderia multivorans infection, including pneumonia, in two animal infection models. These results suggest that [68Ga]Ga-ORNB is a promising tool for the diagnosis, monitoring, and evaluation of the therapeutic response to B. cepacia complex infection.

Mineral Nutrient Uptake, Accumulation, and Distribution in Cunninghamia lanceolata in Response to Drought Stress.

Mineral accumulation in plants under drought stress is essential for drought tolerance. The distribution, survival, and growth of Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.), an evergreen conifer, can be affected by climate change, particularly seasonal precipitation and drought. Hence, we designed a drought pot experiment, using 1-year-old Chinese fir plantlets, to evaluate drought effects under simulated mild drought, moderate drought, and severe drought, which corresponds to 60%, 50%, and 40% of soil field maximum moisture capacity, respectively. A treatment of 80% of soil field maximum moisture capacity was used as control. Effects of drought stress on mineral uptake, accumulation, and distribution in Chinese fir organs were determined under different drought stress regimes for 0-45 days. Severe drought stress significantly increased phosphorous (P) and potassium (K) uptake at 15, 30 and 45 days, respectively, within fine (diameter < 2 mm), moderate (diameter 2-5 mm), and large (diameter 5-10 mm) roots. Drought stress decreased magnesium (Mg) and manganese (Mn) uptake by fine roots and increased iron (Fe) uptake in fine and moderate roots but decreased Fe uptake in large roots. Severe drought stress increased P, K, calcium (Ca), Fe, sodium (Na), and aluminum (Al) accumulation in leaves after 45 days and increased Mg and Mn accumulation after 15 days. In stems, severe drought stress increased P, K, Ca, Fe, and Al in the phloem, and P, K, Mg, Na, and Al in the xylem. In branches, P, K, Ca, Fe, and Al concentrations increased in the phloem, and P, Mg, and Mn concentrations increased in the xylem under severe drought stress. Taken together, plants develop strategies to alleviate the adverse effects of drought stress, such as promoting the accumulation of P and K in most organs, regulating minerals concentration in the phloem and xylem, to prevent the occurrence of xylem embolism. The important roles of minerals in response to drought stress should be further evaluated.

Evaluation of proximate compositions and heavy metal concentrations of Amaranthus spinosus L. and Talinum fruticosum (L.) Juss. harvested on some poultry dumpsites in Badagry, Lagos State, Nigeria

Abstract Poultry waste as enhancement for crop development has become a norm for nutrients’ source but their pollution potentials is a source for concern. Thus, this study aimed at assessing proximate compositions and heavy metal accumulation in organs of Amaranthus spinosus and Talinum fruticosum handpicked from three poultry faecal sites in Badagry, Lagos State. Leaves and roots of A. spinosus and T. fruticosum as well as soil samples were collected from Yafin, Agric and Badagry dumpsites in Badagry Local Government and these were subjected to proximate and heavy metal analyses using standard analytical procedures. Data obtained were analyzed using mean-standard deviation. Proximate analyses of A. spinosus and T. fruticosum from three faecal sites contained appreciable Moisture, protein, carbohydrate, fiber, ash, and fat contents. Also, heavy metal analyses of the vegetables from the three faecal sites ranged as follows: Cd: 0.01-0.05mg/100g in leaves; 0.04-0.12mg/100g in roots, Co: 0.04-0.05 in leaves; 0.04-0.12mg/100g in roots, Cr: 0.58-0.84mg/100g in leaves; 0.91-1.01mg/100g in roots, Cu: 0.27-70.51mg/100g in leaves; 0.50-58.55mg/100g in roots for A. spinosus; Cd: 0.04-0.07mg/100g in leaves; 0.06-0.12mg/100g in roots, Co: 0.02-0.06mg/100g in leaves; 0.08-0.34mg/100g in roots, Cr: 0.05-0.12mg/100g in leaves; 0.04-0.23mg/100g in roots, Cu: 61.55-121.81mg/100g in leaves; 48.45-147.45mg/100g in roots for T. fruticosum and Cd: 3.53-9.05mg/100g, Co: 0.14-0.69mg/100g, Cr:0.14-4.22mg/100g: and Cu: 2.59-8.11mg/100g in soils for all three dumpsites sampled. However, all metals analysed were below WHO limits for vegetable and soils except cobalt, copper and chromium. Thus, locals should be advised against consumption of vegetables from dumpsites since toxic substances often accumulates in the environment and maybe hazardous to man’s health.

The Accumulation of Health-Promoting Nutrients from Representative Organs across Multiple Developmental Stages in Orange Chinese Cabbage.

Orange Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an excellent source of health-promoting nutrients that could reduce the risk of chronic diseases. This study mainly investigated the accumulation patterns of eight lines of orange Chinese cabbage for indolic glucosinolates (GLSs) and pigment content from representative plant organs across multiple developmental stages. The indolic GLSs were highly accumulated at the rosette stage (S2), especially in inner and middle leaves, and the order of indolic GLSs accumulation in non-edible organs was flower > seed > stem > silique. The expression levels of biosynthetic genes in light signaling, MEP, carotenoids, and GLS pathways were consistent with the metabolic accumulation patterns. The results of a principal component analysis show a clear separation of high indolic GLS lines (15S1094 and 18BC6) from low indolic GLS lines (20S530). A negative correlation between the accumulation of indolic GLS and carotenoids was identified in our study. Our work contributes to providing valuable knowledge required to breed, grow, and select orange Chinese cabbage varieties and their eatable organs with higher nutritional value.

Dapaglifozin on Albuminuria in Chronic Kidney Disease Patients with FabrY Disease: The DEFY Study Design and Protocol.

Fabry disease (FD) is a rare genetic disorder caused by a deficiency in the α-galactosidase A enzyme, which results in the globotriaosylceramide accumulation in many organs, including the kidneys. Nephropathy is a major FD complication that can progress to end-stage renal disease if not treated early. Although enzyme replacement therapy and chaperone therapy are effective, other treatments such as ACE inhibitors and angiotensin receptor blockers can also provide nephroprotective effects when renal damage is also established. Recently, SGLT2 inhibitors have been approved as innovative drugs for treating chronic kidney disease. Thus, we plan a multicenter observational prospective cohort study to assess the effect of Dapagliflozin, a SGLT2 inhibitor, in FD patients with chronic kidney disease (CKD) stages 1-3. The objectives are to evaluate the effect of Dapagliflozin primarily on albuminuria and secondarily on kidney disease progression and clinical FD stability. Thirdly, any association between SGT2i and cardiac pathology, exercise capacity, kidney and inflammatory biomarkers, quality of life, and psychosocial factors will also be evaluated. The inclusion criteria are age ≥ 18; CKD stages 1-3; and albuminuria despite stable treatment with ERT/Migalastat and ACEi/ARB. The exclusion criteria are immunosuppressive therapy, type 1 diabetes, eGFR < 30 mL/min/1.73 m2, and recurrent UTIs. Baseline, 12-month, and 24-month visits will be scheduled to collect demographic, clinical, biochemical, and urinary data. Additionally, an exercise capacity and psychosocial assessment will be performed. The study could provide new insights into using SGLT2 inhibitors for treating kidney manifestations in Fabry disease.

Accumulation of Microplastics in the Digestive Tract and Gonads and its Effects on Gonad Quality of Sea urchins Tripnesutes gratilla

Marine plastic debris that is transported will move with the flow of water and float and then be degraded into smaller particles, namely microplastics, sink and settle on the substrate. Sea urchins as deposit feeders have the potential to ingest microplastic particles, where these particles can influence changes in behavior, growth, enzyme production, reproduction, and tissue structure. This study used a purposive sampling method with descriptive analysis for data related to the recording of morphometrics and gonadal quality as well as follow-up tests of the Tukey test and Pearson test. This study aims to analyze how the accumulation of microplastics in organs (digestive tract and gonads) affects the gonadal quality of sea urchins Tripneustes gratilla. The results showed that the number of microplastic particles found in the digestive tract of sea urchins was 233 particles/individual and in the gonads were 205 particles/individual with the color variants transparent, multicolor, blue, yellow, red, green, and purple. Gonadal quality assessment indicators are color, firmness, and gonadal index. Gonads with good quality were shown by sea urchins from Laha beach (site 1) with a composition of 40% bright orange, 40% yellow/pale yellow, 20% bright orange, very firm 80% and not firm20%, and a gonadal index value of 7.57 %. In contrast, gonads with poor quality were shown by sea urchins from Erie beach (site 4) with a composition of 80% brown and 20% gray, a very firm of 60% and 40% firm, and a gonadal index value of 3.08%. This difference in quality is thought to be the result of microplastic accumulation in the sea urchin organs which causes the satiated delusion.

Analysis of organic acid metabolism reveals citric acid and malic acid play major roles in determining acid quality during the development of kiwifruit (Actinidia eriantha).

Actinidia eriantha is one of the most important kiwifruit species in Actinidia. The relative high accumulation of organic acids in fruit of A. eriantha is an unfavorable factor for organoleptic quality. To identify key metabolic enzymes and genes involved in organic acids accumulation during fruit development, physiological, biochemical, and molecular experiments were conducted for the dynamic fruit samples of a new kiwifruit cultivar, A. eriantha 'Ganlv 1'. The contents of citric acid and malic acid increased greatly during fruit development, while quinic acid content decreased obviously. Significant positive correlations were observed between fruit titratable acidity and the contents of both citric acid and malic acid, and a significant negative correlation was found between fruit titratable acidity and the quinic acid content. The high accumulation of citric acid was found to be caused by the increased activity of citrate synthase (CS), and the decreased activities of two degradation-related enzymes, mitochondrial aconitase and nicotinamide adenine dinucleotide (NAD)-dependent isocitrate dehydrogenase. In addition, the accumulation of malic acid depended mainly on the increased synthesis catalyzed by NAD-dependent malate dehydrogenase (NAD-MDH) and phosphoenolpyruvate carboxylase. Further analysis suggested that AeCS2 and AeMDH2 played pivotal roles in controlling the activities of CS and NAD-MDH respectively. The high accumulation level of citric acid relied on both the strong synthesis ability and the weak degradation ability. The accumulation level of malic acid was mainly affected by the synthesis. The novel information would be helpful for our understanding of the formation of fruit acidity quality. © 2023 Society of Chemical Industry.

Imaging Plate Autoradiography for Ingested Anthropogenic Cesium-137 in Butterfly Bodies: Implications for the Biological Impacts of the Fukushima Nuclear Accident.

The Fukushima nuclear accident in March 2011 caused biological impacts on the pale grass blue butterfly Zizeeria maha. At least some of the impacts are likely mediated by the host plant, resulting in "field effects". However, to obtain the whole picture of the impacts, direct exposure effects should also be evaluated. Here, we examined the distribution of experimentally ingested anthropogenic cesium-137 (137Cs) in adult butterfly bodies using imaging plate autoradiography. We showed that 137Cs ingested by larvae was incorporated into adult bodies and was biased to females, although the majority of ingested 137Cs was excreted in the pupal cuticle and excretory material during eclosion. 137Cs accumulation in adult bodies was the highest in the abdomen, followed by the thorax and other organs. These results suggest that 137Cs accumulation in reproductive organs may cause adverse transgenerational or maternal effects mediated by reactive oxygen species (ROS) on germ cells. 137Cs accumulation was detected in field individuals collected in September 2011 and September 2016 but not in May 2011, which is consistent with the abnormality dynamics known from previous studies. Taken together, these results contribute to an integrative understanding of the multifaceted biological effects of the Fukushima nuclear accident in the field.

Hydrogen peroxide reduces root cadmium uptake but facilitates root-to-shoot cadmium translocation in rice through modulating cadmium transporters

Cadmium (Cd) contamination in agricultural soils has become a serious worldwide environmental problem threatening crop production and human health. Hydrogen peroxide (H2O2) is a critical second messenger in plant response to Cd exposure. However, its role in Cd accumulation in various organs of plants and the mechanistic basis of this regulation remains to be elucidated. In this study, we used electrophysiological and molecular approaches to understand how H2O2 regulates Cd uptake and translocation in rice plants. Our results showed that the pretreatment of H2O2 significantly reduced Cd uptake by rice roots, which was associated with the downregulation of OsNRAMP1 and OsNRAMP5. On the other hand, H2O2 promoted the root-to-shoot translocation of Cd, which might be attributed to the upregulation of OsHMA2 critical for Cd2+ phloem loading and the downregulation of OsHMA3 involved in the vacuolar compartmentalization of Cd2+, leading to the increased Cd accumulation in rice shoots. Furthermore, such regulatory effects of H2O2 on Cd uptake and translocation were notably amplified by the elevated level of exogenous calcium (Ca). Collectively, our results suggest that H2O2 can inhibit Cd uptake but increase root to shoot translocation through modulating the transcriptional levels of genes encoding Cd transporters, furthermore, application of Ca can amplify this effect. These findings will broaden our understanding of the regulatory mechanisms of Cd transport in rice plants and provide theoretical foundation for breeding rice for low Cd accumulation.

Small Ceria Nanoclusters with High ROS Scavenging Activity and Favorable Pharmacokinetic Parameters for the Amelioration of Chronic Kidney Disease.

The over production of reactive oxygen species (ROS) plays a critical role in the progression of chronic kidney disease (CKD). Organic ROS scavengers currently used for CKD treatment do not satisfy low dosage and high efficiency requirements. Ceria nanomaterials featured with renewable ROS scavenging activity are potential candidates for CKD treatment. Herein, a method for the synthesis of ceria nanoclusters (NCs) featured with small size of ≈1.2 nm is reported. The synthesized NCs are modified by three hydrophilic ligands with different molecular weights, including succinic acid (SA), polyethylene glycol diacid 600 (PEG600), and polyethylene glycol diacid 2000 (PEG2000). The surface modified NCs exhibit excellent ROS scavenging activity due to the high Ce3+ /Ce4+ ratio in their crystal structures. Compared with bigger-sized ceria nanoparticles (NPs) (≈45 nm), NCs demonstrate smoother blood concentration-time curve, lower organ accumulation, and faster metabolic rate superiorities. The administration of NCs to CKD mice, especially PEG600 and PEG2000 modified NCs, can effectively inhibit oxidative stress, inflammation, renal fibrosis, and apoptosis in their kidneys. Due to these benefits, the constructed NCs can ameliorate the progression of CKD. These findings suggest that NCs is a potential redox nanomedicine for future clinical treatment of CKD.

Improving ultrafiltration of algae-laden water with chitosan quaternary ammonium salt enhanced by sodium percarbonate

Ultrafiltration (UF) is extensively used for algae removal because of its ability to retain algal cells with high efficiency, but it still faces the problem of membrane fouling and low retention capacity of dissolved organics. Hence, a strategy of coagulation with chitosan quaternary ammonium salt (HTCC) enhanced by sodium percarbonate (SPC) pre-oxidation was proposed to improve the UF performance. The fouling resistances were calculated by a resistance-in-series model based on Darcy's formula, and the membrane fouling mechanism was evaluated using a pore plugging-cake filtration model. The effect of SPC-HTCC treatment on the properties of algal foulants was explored, and the result showed that the water quality was improved with the maximum removal rates of 78.8 %, 52.4 % and 79.5 % for algal cells, dissolved organic carbon and turbidity, respectively. The SPC could achieve a mild oxidation effect that degraded the electronegative organics attached to algal cells without destroying the cell integrity, making the algal pollutants easier to agglomerate through subsequent HTCC coagulation by forming larger flocs. In terms of membrane filtration, the terminal normalized flux was increased from 0.25 to 0.71, with the reversible and irreversible resistances reduced by 90.8 % and 40.2 %, individually. The synergistic treatment reduced the accumulation of algal cells and algae-derived organics on the membrane surface as inferred from the interface fouling characteristics. The interfacial free energy analysis showed that the synergistic treatment reduced the adhesion of contaminants to the membrane surface, as well as the attraction among pollutants. Overall, the proposed process has high application prospects for algae-laden water purification.

Early afforestation on islands of proglacial Lake Ojibway as evidence of post-glacial migration outposts

At the end of the last glacial period in the northern hemisphere, meltwater from receding ice sheets accumulated into large proglacial lakes, potentially limiting postglacial afforestation. We explored whether former islands of proglacial Lake Ojibway (Canada) (hilltops in the current landscape) could have acted as migration outposts and thus accelerated the postglacial migration. We extracted sediments from two small lakes located on “paleo-islands” and used XRF to detect changes in soil erosion and vegetation biomass. We also used plant macro-remains and wood charcoal to determine if (and which) tree species colonized the sites and to detect local fire events. Organic sediment accumulation started around 9657 and 9947 cal. yr BP at Lakes Perché and Despériers, respectively, before the level of Lake Ojibway started to decrease and liberate parts of the studied landscape ca 9400 cal. yr BP. Lithogenic elements (Ti, K, Sr, Fe, Zr, and Rb) decreased between the beginning of organic sediment accumulation and 8800–8700 cal. yr BP, indicating reduced soil erosion, possibly due to soil stabilization by vegetation. Then, the S/Ti ratio, a proxy of organic matter increased around 8800 and 8400 cal. yr BP. The earliest tree macro-remains ( Larix laricina and Pinus spp.) were found between 9850 and 9500 cal. yr BP. Local fires were detected around 9820 and 8362 cal. yr BP. Early afforestation occurred on the islands of Lake Ojibway, 200 and 450 years before its level started to decrease, confirming that some islands acted as migratory outposts accelerating postglacial migration.

H2S Crosstalk in Rhizobia Modulates Essential Nutrient Allocation and Transport in Soybean

Hydrogen sulfide (H2S), a novel gas signaling molecule, plays a crucial role in plant growth and stress response. However, little attention has been devoted to the regulation of H2S on nutrient transport and utilization in legume–rhizobia symbiosis systems. Although we have previously proven that H2S synergized with rhizobia to considerably enhance nitrogen (N) metabolism and remobilization in N-deficient soybeans, it remains uncertain if changes in nutrient absorption, metabolism, and accumulation occur concurrently. Therefore, employing a synergistic treatment of H2S and rhizobia, we examined the dry matter biomass and carbon (C), N, phosphorous (P), and potassium (K) nutrient content in various organs of soybean from blooming to maturity. Firstly, H2S and rhizobia application obviously improved leaf and plant phenotypes and biomass accumulation in different organs during N-deficient soybean development. Second, from flowering to maturity, the contents and stoichiometric ratios of C, N, P, and K in various organs of soybean were changed to variable degrees by H2S and rhizobia. Furthermore, H2S collaborated with rhizobia to significantly affect grain nutrient harvest across soybean growth as well as overall plant nutrient accumulation. Consequently, H2S synergizes with rhizobia to optimize grain harvest quality and nutrient accumulation across the plant by managing the rational allocation and dynamic balance of nutrients in diverse organs, hence boosting soybean development and production.

PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role

BackgroundDelayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored.MethodsPeripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry.ResultsPD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis.ConclusionIn this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.

Induction of macrophages matriptase and activation of macrophage stimulating protein 1 in sickle cell anemia - related chronic kidney disease

BACKGROUND: More than 50% of sickle cell anemia (SCA) patients develop chronic kidney disease (CKD). The mechanism of CKD is multifactorial and is not yet fully understood. SCA is a vasculopathy associated with multiple mechanisms driven by cell-free mutated hemoglobin (HbS). We have demonstrated that activation of recepteur d'origine nantais (RON) kinase contributes to the renal endothelial injury in SCA mouse model. Inhibition of RON reduces endothelial injury and ameliorates renal disease. Macrophage-stimulating protein 1 (MSP1) is the only known ligand for RON. MSP1 is synthesized by the liver and released in the circulation as biologically inactive pro-MSP1 protein that is activated by proteolytic cleavage. Macrophage membrane matriptase (MT-SP1) cleaves MSP1, making it able to bind RON receptor. The levels of plasma MSP1 and macrophage MT-SP1 in SCA have not been investigated. OBJECTIVES: To evaluate MT-SP1 expression and serum MSP1 levels in SCA patients and mouse model. HYPOTHESIS: The level of circulating MSP1 is reduced in SCA patients and mice due to its accumulation in organs. METHODS: The study was approved by Howard University IRB.All subjects provided written informed consent. Whole blood samples were obtained from 44 SCA patients enrolled at HU CSCD Registry study and 6 healthy control individuals. SCA mice (Townes) were housed in Howard University; the animal protocol was approved by the IACUC. ELISA kits were used to test human and mouse MSP1. Human THP-1 promonocytic cells were differentiated into macrophages with 25 nM PMA for 72 hrs and treated with either purified HbS or HbA (5 μM). Total RNA was used for RNA Seq. Comparisons were conducted using Dragen differential expression software v. 3.6.3 (Illumina), and gene counts were normalized using DESeq2 package from Bioconductor. RESULTS: RNA Seq results demonstrated increased levels of MT-SP1 in THP-1-derived macrophages after treatment with HbS compared to treatment with normal hemoglobin (HbA) (p=0.036). The results were further confirmed by real-time RT-PCR. The levels of plasma MSP1 were about 7-fold lower in SCD patients compared to non-SCD controls (146.8±111.7 ng/ml, N=6 in control vs. 20.6 ng/ml, N=44 in SCD, p=3.97x10-10). Log2 (MSP1) slightly correlated with albuminuria log2 (ALB/CRE) (r=0.1243, R2=0.0154, p=0.4216, N=44). This correlation was more profound in females (r=0.3158, R2=0.0997, p=0.1632, N=21). No correlation was found in males. We found moderate inverted correlation between eGFR and log2 (MSP1) (r=-0.3313, R2=0.1094, p=0.0280, N=44). In SCA patients with renal disease, MSP1 levels positively correlated with stages of CKD (r=0.3990, R2=0.1592, p=0.0320, N=29). In mouse, serum MSP1 levels were about 2.3-fold reduced in SCA compared to control mice (441.0±97.98 ng/ml, N=5 in control vs. 192.2 ±27.02, N=7 in SCD, p=0.0173). Immunostaining demonstrated the high levels of MSP1 accumulation on the surface of endothelial cells in the ki This work was supported by NIH Research Grants SC1HL150685, P50HL118006, R01HL125005, and G12MD007597. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.