Characterisation of experimental flowable composites containing fluoride-doped calcium phosphates as promising remineralising materials.

OBJECTIVE: Remineralising composites with antibacterial properties may seal the cavity and prevent secondary caries. This study aimed at developing experimental flowable composites containing different concentrations of fluoride-doped calcium phosphate fillers and evaluating their remineralising and antibacterial properties. METHODS: Experimental resin-based composites containing different concentrations (0-20 %) of fluoride-doped calcium phosphate fillers (VS10/VS20) were formulated. The release of calcium (Ca), phosphate (PO) and fluoride (F) ions was assessed for 30 days. Remineralisation properties were evaluated through ATR-FTIR and SEM/EDX after storage in simulated body fluid (SBF). The metabolic activity and viability of Streptococcus gordonii was also evaluated through ATP, CFU and live/dead confocal microscopy. The evaluation of specific monomer elution from the experimental composites was conducted using high-performance liquid chromatography (HPLC). RESULTS: The composites containing VS10 showed the highest release of Ca, those containing VS20 released more F over time (p < 0.05), while there was no significant difference in terms of PO ions release between the groups (p > 0.05). A quick 7-day mineral precipitation was observed in the tested composites containing VS10 or VS20 at 10 %; these materials also showed the greatest antibacterial activity (p < 0.05). Moreover, the tested composites containing VS10 presented the lowest elution of monomers (p < 0.05). CONCLUSIONS: Innovative composites were developed with low monomers elution, evident antibacterial activity against S. gordonii and important remineralisation properties due to specific ions release. CLINICAL SIGNIFICANCE: Novel composites containing fluoride-doped calcium phosphates may be promising to modulate bacteria growth, promote remineralisation and reduce the risk of cytotoxicity related to monomers' elution.

Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups.

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.

Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation.

The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive 31P-MRS scans, 1H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.

Copper-doped magnesium phosphate nanopowders for critical size calvarial bone defect intervention.

Calvarial defects of bone present difficult clinical situations, and their restoration using biocompatible materials requires special treatments that enable bone regeneration. Magnesium phosphate (MgP) is known as an osteoinductive biomaterial because it contains Mg2+ ions and P ions that enhance the activity of osteoplast cells and help in bone regeneration. In this study, MgP and CuO-doped MgP were fabricated and characterized for their physicomechanical properties, particle size, morphology, surface area, antibacterial test, and in vitro bioactivity evaluation using the following techniques: X-rays diffraction, Fourier-transformer infrared, TEM, and Brunauer, Emmett and Teller (BET) surface area, X-rays photoelectron spectroscopy (XPS), and Scanning electron microscopy (SEM). Furthermore, these nanopowders were implanted in adult inbred male Wistar rats and studied after two periods (28 and 56 days). The results demonstrated that the obtained semiamorphous powders are in nanoscale (≤ 50 nm). XPS analysis ensured the preparation of MgP as mono MgP and CuO were incorporated in the structure as Cu2+ . The bioactivity was supported by the observation of calcium phosphate layer on the nanopowders' surface. The in vivo study demonstrated success of MgP nanopowders especially those doped with CuO in restoration of calvarial defect bone. Therefore, fabricated biomaterials are of great potential in restoration of bone calvarial defects.

Tris(1,3-dichloro-2-propyl) phosphate induces endoplasmic reticulum stress and mitochondrial-dependent apoptosis in mouse spermatocyte GC-2 cells.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a frequently detected organophosphorus flame retardants (OPFRs) in various environmental media, and has been evidenced as reproductive toxicity. However, its adverse effects on spermatogenic cells are unknown. In this study, mouse spermatocyte GC-2spd (GC-2) cells were selected as an in vitro model, and the impact of mitochondrial structure and function, endoplasmic reticulum (ER) stress, cell apoptosis and the related molecular mechanisms were investigated. Our study indicated that cell viability was decreased significantly in a dose-dependent manner after TDCIPP treatment with the half lethal concentration (LC50) at 82.8 µM, 50.0 µM and 39.6 µM for 24 h, 48 h and 72 h, respectively. An apoptosis was observed by Annexin V-FITC/PI stain. In addition, fragmentation of mitochondrial structure, an increase of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, release of cytochrome c and activation of Caspase-3 and Caspase-9 activity implicated that Caspase-3 dependent mitochondrial pathway might play a key role in the process of GC-2 cell apoptosis. Furthermore, ER stress induction was convinced by altered morphology of ER and up-regulation of ER targeting genes, including (Bip, eIF2α, ATF4, XBP1, CHOP, ATF6 and Caspase-12). Taken together, these results demonstrate that both mitochondrial apoptotic pathways and ER stress apoptotic pathways might play important roles in the process of apoptosis in GC-2 cells induced by TDCIPP treatment. Therefore, the potential reproductive toxicity of TDCIPP should not be ignored.

Sucrose-phosphate osmotic system improves the quality characteristics of reduced-salt salted egg yolk: Profiling from protein structure and lipid distribution perspective.

This paper was dedicated to the study of the effect of sucrose-phosphate on aspects of physicochemical properties, lipid distribution and protein structure during the picklig of reduced-salt salted egg yolk (SEY). This work constructed a reduced-salt pickling system from a new perspective (promoting osmosis) by using a sucrose-phosphate-salt. Results showed that SEY-28d achieved a desirable salt content (1.07 %), hardness (573.46 g) and springiness (0.65 g). The matured SEY was in excellent quality with orange-red color and loose sandy texture. This was because the lipoprotein aggregated with each other through hydrophobic interaction to form a stable network structure. In addition, the hypertonic environment accelerated salt penetration. These also created good condition for lipid spillage. The results of confocal laser scanning microscope also verified this phenomenon. This work provides important guidance for new reduced-salt curing of traditional pickled foods, deep processing of SEY, and industry development in the field of poultry egg.

Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification.

BACKGRUOUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system. METHODS: To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide. RESULTS: Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs. CONCLUSION: These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.

Cresyl Diphenyl Phosphate exposure induces reproductive functional defects in men and male mice.

Cresyl Diphenyl Phosphate (CDP), as a novel organophosphate esters (OPEs), achieves widely used and exposed in multiple industries. However, its male reproductive toxicity and underlying mechanism remains unclear. In vivo, male mice were gavaged with CDP (0, 4, 20, or 100 mg/kg/d) for 8 weeks. And we treated TM3, TM4 and GC-2 cells with 0, 10, 25, and 50 µM CDP for 24 h to detect its reproductive toxicity effect in vitro. In our study, we revealed that CDP inhibited proliferation and induced apoptosis in mice testis and GC-2 cells, thereby leading to the decreased sperm quality. In mechanism, CDP trigger the oxidative stress and ROS production, thus partially causing DNA damage and cell apoptosis. Moreover, CDP exposure causes injury to Ledyig cells and Sertoli cells, thus disturbing the testicular microenvironment and inhibiting spermatogonia proliferation. In conclusion, this research reveals multiple adverse impacts of CDP on the male reproductive system and calls for further study of the toxicological effects of CDP on human health.

Characterization of the Pneumocystis jirovecii and Pneumocystis murina phosphoglucomutases (Pgm2s): a potential target for Pneumocystis therapy.

Pneumocystis cyst life forms contain abundant ß-glucan carbohydrates, synthesized using ß-1,3 and ß-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose. In yeast, phosphoglucomutase (PGM) plays a crucial role in carbohydrate metabolism by interconverting glucose 1-phosphate and glucose 6-phosphate, a vital step in UDP pools for ß-glucan cell wall formation. This pathway has not yet been defined in Pneumocystis. Herein, we surveyed the Pneumocystis jirovecii and Pneumocystis murina genomes, which predicted a homolog of the Saccharomyces cerevisiae major PGM enzyme. Furthermore, we show that PjPgm2p and PmPgm2p function similarly to the yeast counterpart. When both Pneumocystis pgm2 homologs are heterologously expressed in S. cerevisiae pgm2Δ cells, both genes can restore growth and sedimentation rates to wild-type levels. Additionally, we demonstrate that yeast pgm2Δ cell lysates expressing the two Pneumocystis pgm2 transcripts individually can restore PGM activities significantly altered in the yeast pgm2Δ strain. The addition of lithium, a competitive inhibitor of yeast PGM activity, significantly reduces PGM activity. Next, we tested the effects of lithium on P. murina viability ex vivo and found the compound displays significant anti-Pneumocystis activity. Finally, we demonstrate that a para-aryl derivative (ISFP10) with known inhibitory activity against the Aspergillus fumigatus PGM protein and exhibiting 50-fold selectivity over the human PGM enzyme homolog can also significantly reduce Pmpgm2 activity in vitro. Collectively, our data genetically and functionally validate phosphoglucomutases in both P. jirovecii and P. murina and suggest the potential of this protein as a selective therapeutic target for individuals with Pneumocystis pneumonia.

Mycorrhizal fungus Serendipita indica-associated acid phosphatase rescues the phosphate nutrition with reduced arsenic uptake in the host plant under arsenic stress.

Symbiotic interactions play a vital role in maintaining the phosphate (Pi) nutrient status of host plants and providing resilience during biotic and abiotic stresses. Serendipita indica, a mycorrhiza-like fungus, supports plant growth by transporting Pi to the plant. Despite the competitive behaviour of arsenate (AsV) with Pi, the association with S. indica promotes plant growth under arsenic (As) stress by reducing As bioavailability through adsorption, accumulation, and precipitation within the fungus. However, the capacity of S. indica to enhance Pi accumulation and utilization under As stress remains unexplored. Axenic studies revealed that As supply significantly reduces intracellular ACPase activity in S. indica, while extracellular ACPase remains unaffected. Further investigations using Native PAGE and gene expression studies confirmed that intracellular ACPase (isoform2) is sensitive to As, whereas extracellular ACPase (isoform1) is As-insensitive. Biochemical analysis showed that ACPase (isoform1) has a Km of 0.5977 µM and Vmax of 0.1945 Unit/min. In hydroponically cultured tomato seedlings, simultaneous inoculation of S. indica with As on the 14thday after seed germination led to hyper-colonization, increased root/shoot length, biomass, and induction of ACPase expression and secretion under As stress. Arsenic-treated S. indica colonized groups (13.33 µM As+Si and 26.67 µM As+Si) exhibited 8.28-19.14 and 1.71-3.45-fold activation of ACPase in both rhizospheric media and root samples, respectively, thereby enhancing Pi availability in the surrounding medium under As stress. Moreover, S. indica (13.33 µM As+Si and 26.67 µM As+Si) significantly improved Pi accumulation in roots by 7.26 and 9.46 times and in shoots by 4.36 and 8.85 times compared to the control. Additionally, S. indica induced the expression of SiPT under As stress, further improving Pi mobilization. Notably, fungal colonization also restricted As mobilization from the hydroponic medium to the shoot, with a higher amount of As (191.01 ppm As in the 26.67 µM As+Si group) accumulating in the plant's roots. The study demonstrates the performance of S. indica under As stress in enhancing Pi mobilization while limiting As uptake in the host plant. These findings provide the first evidence of the As-Pi interaction in the AM-like fungus S. indica, indicating reduced As uptake and regulation of PHO genes (ACPase and SiPT genes) to increase Pi acquisition. These data also lay the foundation for the rational use of S. indica in agricultural practices.

BMP2 restores erectile dysfunction through neurovascular regeneration and fibrosis reduction in diabetic mice.

BACKGROUND: The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase-5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis. OBJECTIVES: To assess the efficacy of bone morphogenetic protein 2 in stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction. MATERIALS AND METHODS: The induction of diabetes mellitus was performed by streptozotocin (50 mg/kg daily) administered intraperitoneally for 5 successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post-inductions, animals were allocated to one of five groups: a control group, a streptozotocin-induced diabetic mouse group receiving two intracavernous 20 µL phosphate-buffered saline injections, or one of three bone morphogenetic protein 2 groups administered two injections of bone morphogenetic protein 2 protein (1, 5, or 10 µg) diluted in 20 µL of phosphate-buffered saline within a 3-day interval between the first and second injections. The erectile functions were assessed 2 weeks after phosphate-buffered saline or bone morphogenetic protein 2 protein injections by recording the intracavernous pressure through cavernous nerve electrical stimulation. Angiogenic activities and nerve regenerating effects of bone morphogenetic protein 2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured mouse cavernous endothelial cells. Moreover, fibrosis-related factor protein expressions were evaluated by western blotting. RESULTS: Erectile function recovery to 81% of the control value in diabetic mice was found with intracavernous bone morphogenetic protein 2 injection (5 µg/20 µL). Pericytes and endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with bone morphogenetic protein 2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of mouse cavernous endothelial cells. Bone morphogenetic protein 2 protein enhanced cell proliferation and reduced apoptosis in mouse cavernous endothelial cells and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, bone morphogenetic protein 2 suppressed fibrosis by reducing mouse cavernous endothelial cell fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions. CONCLUSION: Bone morphogenetic protein 2 modulates neurovascular regeneration and inhibits fibrosis to revive the mouse erection function in diabetic conditions. Our findings propose that the bone morphogenetic protein 2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction.

Elevated extracellular inorganic phosphate inhibits ecto-phosphatase activity in breast cancer cells: Regulation by hydrogen peroxide.

For cells to obtain inorganic phosphate, ectoenzymes in the plasma membrane, which contain a catalytic site facing the extracellular environment, hydrolyze phosphorylated molecules. In this study, we show that increased Pi levels in the extracellular environment promote a decrease in ecto-phosphatase activity, which is associated with Pi-induced oxidative stress. High levels of Pi inhibit ecto-phosphatase because Pi generates H2 O2 . Ecto-phosphatase activity is inhibited by H2 O2 , and this inhibition is selective for phospho-tyrosine hydrolysis. Additionally, it is shown that the mechanism of inhibition of ecto-phosphatase activity involves lipid peroxidation. In addition, the inhibition of ecto-phosphatase activity by H2 O2 is irreversible. These findings have new implications for understanding ecto-phosphatase regulation in the tumor microenvironment. H2 O2 stimulated by high Pi inhibits ecto-phosphatase activity to prevent excessive accumulation of extracellular Pi, functioning as a regulatory mechanism of Pi variations in the tumor microenvironment.

Synthesis and biological evaluation of structurally diverse 6-aryl-3-aroyl-indole analogues as inhibitors of tubulin polymerization.

The synthesis and evaluation of small-molecule inhibitors of tubulin polymerization remains a promising approach for the development of new therapeutic agents for cancer treatment. The natural products colchicine and combretastatin A-4 (CA4) inspired significant drug discovery campaigns targeting the colchicine site located on the beta-subunit of the tubulin heterodimer, but so far these efforts have not yielded an approved drug for cancer treatment in human patients. Interest in the colchicine site was enhanced by the discovery that a subset of colchicine site agents demonstrated dual functionality as both potent antiproliferative agents and effective vascular disrupting agents (VDAs). Our previous studies led to the discovery and development of a 2-aryl-3-aroyl-indole analogue (OXi8006) that inhibited tubulin polymerization and demonstrated low nM IC50 values against a variety of human cancer cell lines. A water-soluble phosphate prodrug salt (OXi8007), synthesized from OXi8006, displayed promising vascular disrupting activity in mouse models of cancer. To further extend structure-activity relationship correlations, a series of 6-aryl-3-aroyl-indole analogues was synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity against human cancer cell lines. Several structurally diverse molecules in this small library were strong inhibitors of tubulin polymerization and of MCF-7 and MDA-MB-231 human breast cancer cells. One of the most promising analogues (KGP591) caused significant G2/M arrest of MDA-MB-231 cells, disrupted microtubule structure and cell morphology in MDA-MB-231 cells, and demonstrated significant inhibition of MDA-MB-231 cell migration in a wound healing (scratch) assay. A phosphate prodrug salt, KGP618, synthesized from its parent phenolic precursor, KGP591, demonstrated significant reduction in bioluminescence signal when evaluated in vivo against an orthotopic model of kidney cancer (RENCA-luc) in BALB/c mice, indicative of VDA efficacy. The most active compounds from this series offer promise as anticancer therapeutic agents.

Phosphorylation modification of bovine bone collagen peptide enhanced its effect on mineralization of MC3T3-E1 cells via improving calcium-binding capacity.

This study aimed to investigate the effect of phosphorylation modification of collagen peptide on its calcium-binding capacity and pro-mineralization activity. In this study, collagen peptide (Leu-Thr-Phe, LTF) and phosphorylated LTF (P-LTF) were synthesized and further chelated with calcium ions. The results showed that phosphorylation of LTF significantly enhanced its calcium-binding capacity. Spectra analysis revealed that the calcium-binding sites of P-LTF were mainly carbonyl, carboxyl, and phosphate groups. Molecular docking further demonstrated that the phosphate group introduced by phosphorylation enhanced the calcium-binding capacity of LTF by ionic bonds and coordination bonds. The stability analysis results suggested that intestinal fluid could repair the peptide-calcium complex destroyed by gastric fluid. The cell experiment displayed that P-LTF-Ca significantly improved the mineralization activity of MC3T3-E1 cells, and the order of effective influence was P-LTF-Ca > LTF-Ca > P-LTF > LTF. This study provided the theoretical basis for the potential application of phosphorylation modification in improving bone health.

Contrasting effects of MgAl- and MgFe-based layered double hydroxides on phosphorus mobilization and microbial communities in sediment.

The effects of two types of layered double hydroxides (LDH) in-situ treatment on sediment phosphorus (P) mobilization and microbial community's structure were studied comparatively. The results presented that magnesium/aluminum-based (MA) and magnesium/iron (MF)-based LDH displayed great phosphate uptake ability in aqueous solution in a broad pH range of 3-8. The maximum phosphate sorption capacity of MA was 64.89 mg/g, around four times greater than that of MF (14.32 mg/g). Most of phosphate bound by MA and MF is hard to re-liberate under reduction and ordinary pH (5-9) conditions. In the in-situ remediation, the MA and MF capping/amendment both prevented P migration from the sediment to the overlying water (OL-water) under long-term anaerobic conditions, and MA had a better interception efficiency compared to MF in the same application mode. MA amendment significantly reduced mobile P (Mob-P) content in sediment and could remain its stable Mob-P inactivation capacity over a wide pH range. On the contrary, MF amendment increased Mob-P content in sediment and exhibited a variable ability to inactivate Mob-P under elevated pH conditions. MF can decrease Mob-P content at pH of 7 and 11 but increase Mob-P content at pH of 8-10. Under resuspension conditions, MA and MF capping groups still maintained low P levels in OL-water, while MA capping simultaneously showed a certain degree of resistance to sediment resuspension, but it had a weaker stabilizing effect for sediment than MF. Microbial community analysis manifested neither MA nor MF addition observably altered the sediment microbial diversity, but impacted the functional microorganisms' abundance and reshaped the microbial community's structure, intervening the sediment-P stabilization. Viewed from environmental friendliness, control efficiency, stability of P fixation capacity, and application convenience, MA capping wrapped by fabric is more suitable for addressing internal P loading in eutrophic lakes and holds great potential application.

Measuring and Modelling the Effect of Inorganic Phosphate on Cross-bridge Mechanics in Human Cardiac Muscle.

Many common chronic diseases operate at the intersection of metabolic and cardiovascular dysfunction. In order to model the effects of these diseases and investigate underlying causes we are developing a cardiomyocyte model which incorporates both the mechanics and metabolic factors that underlie work done by the heart. In this paper we present the first experimental results from our study measuring mechanical properties in human cardiac trabeculae, including the effect of inorganic phosphate (Pi) on the complex modulus at 37 °C. Extending our previous mathematical model, we have developed a computationally efficient model of cardiac cross-bridge mechanics which is sensitive to changes in cellular Pi. This extended model was parameterised with human cardiac complex modulus data. It captured the changes to cardiac mechanics following an increase in Pi concentration that we measured experimentally, including a reduced elastic modulus and a right-shift in frequency. The human cardiac trabecula we studied had a low sensitivity to Pi compared to what has been previously reported in mammalian cardiac tissue, which suggests that the muscle may have cellular compensatory mechanisms to cope with elevated Pi levels. This study demonstrates the feasibility of our experimental-modelling pipeline for future investigation of mechanical and metabolic effects in the diseased human heart.Clinical Relevance- This study presents the first measurement of the effect of Pi on the stiffness frequency response of human cardiac tissue and extends an experimental-modelling framework appropriate for investigating effects of disease on the human heart.

Biological and chemical nitrification inhibitors exhibited different effects on soil gross N nitrification rate and N2O production: a 15N microcosm study.

Nitrification inhibitors (NIs) are considered as an effective strategy for reducing nitrification rate and related environmental nitrogen (N) loss. However, whether plant-derived biological NIs had an advantage over chemical NIs in simultaneously inhibiting nitrification rate and N2O production remains unclear. Here, we conducted an aerobic 15N microcosmic incubation experiment to compare the effects of a biological NI (methyl 3-(4-hydroxyphenyl) propionate, MHPP) with three chemical NIs, 2-chloro-6-(trichloromethyl) pyridine (nitrapyrin), dicyandiamide (DCD), and 3,4-dimethylpyrazole phosphate (DMPP) on (i) gross N mineralization and nitrification rate and (ii) the relative importance of nitrification and denitrification in N2O emission in a calcareous soil. The results showed that DMPP significantly inhibited m_gross rate (P < 0.05), whereas DCD, nitrapyrin, and MHPP only numerically inhibited it. Gross N nitrification (n_gross) rates were inhibited by 9.48% in the DCD treatment to 51.5% in the nitrapyrin treatment. Chemical NIs primarily affected the amoA gene abundance of ammonia-oxidizing bacteria (AOB), whereas biological NIs affected the amoA gene abundance of ammonia-oxidizing archaea (AOA) and AOB. AOB's community composition was more susceptible to NIs than AOA, and NIs mainly targeted Nitrosospira clusters of AOB. Chemical NIs of DCD, DMPP, and nitrapyrin proportionally reduced N2O production from nitrification and denitrification. However, the biological NI MHPP stimulated short-term N2O emission and increased the proportion of N2O from denitrification. Our findings showed that the influence of NIs on gross N mineralization rate (m_gross) was dependent on the NI type. MHPP exhibited a moderate n_gross inhibitory capacity compared with the three chemical NIs. The mechanisms of chemical and biological NIs inhibiting n_gross can be partly attributed to changes in the abundance and community of ammonia oxidizers. A more comprehensive evaluation is needed to determine whether biological NIs have advantages over chemical NIs in inhibiting greenhouse gas emissions.

Effect of Atmospheric Pressure Plasma Jet Treatments on Magnesium Phosphate Cements: Performance, Characterization, and Applications.

Atmospheric pressure plasma treatments are nowadays gaining importance to improve the performance of biomaterials in the orthopedic field. Among those, magnesium phosphate-based cements (MPCs) have recently shown attractive features as bone repair materials. The effect of plasma treatments on such cements, which has not been investigated so far, could represent an innovative strategy to modify MPCs' physicochemical properties and to tune their interaction with cells. MPCs were prepared and treated for 5, 7.5, and 10 min with a cold atmospheric pressure plasma jet. The reactive nitrogen and oxygen species formed during the treatment were characterized. The surfaces of MPCs were studied in terms of the phase composition, morphology, and topography. After a preliminary test in simulated body fluid, the proliferation, adhesion, and osteogenic differentiation of human mesenchymal cells on MPCs were assessed. Plasma treatments induce modifications in the relative amounts of struvite, newberyite, and farringtonite on the surfaces on MPCs in a time-dependent fashion. Nonetheless, all investigated scaffolds show a good biocompatibility and cell adhesion, also supporting osteogenic differentiation of mesenchymal cells.

Effects of propranolol on glucose metabolism in hemangioma-derived endothelial cells.

Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.

Valorization of phosphate sludge and its bacterial biomass as a potential bioformulation for improving tomato growth.

Phosphorus (P) is a vital limiting nutrient element for plant growth and yield. In Morocco, the natural phosphate rock extractions generate significant amounts of phosphate wash sludge (PS), which could be reused productively, thus creating another added value for farmers. The present study aimed to demonstrate the combination effect of soil amendment by two different PS concentrations (1% and 5%) associated with three phosphate-solubilizing bacteria (PSB) consortia (C1, C2, and C3), isolated from phosphate mining sludge, on plant growth and nutrient uptake in tomato seedlings (Solanum lycopersicum). The results obtained showed that this bioformulation significantly improved P solubilization and plant growth compared to control conditions. Of all the combinations, C3-inoculated soil amended with 5% PS was the most effective in significantly improving plant height and dry and fresh biomass of shoots and roots. P solubilization and its availability for tomato seedlings uptake were maximal with the bioformulation (C3 + 5% PS). This latter enhanced P and potassium (K) uptake by 27.89 and 38.81% in shoots and 38.57% and 74.67% in roots, respectively, compared to non-inoculated soil amended with 5% PS. The highest flowering rate (200 %) was recorded in C3-inoculated soil amended with 5% PS. Supporting these results, the principal component analysis discriminated this bioformulation (C3 + 5% PS) from the other combinations. Our results open up prospects for upgrading phosphate sludge enriched with PSB consortia as a biofertilizer that can be used in ecofriendly agriculture integrated into the circular economy.