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Inhibition of tissue‐nonspecific alkaline phosphatase (TNAP) may prevent ectopic soft tissue calcification by increasing endogenous pyrophosphate (PPi). DS‐1211 is a potent and selective novel small molecule TNAP inhibitor with well‐characterized pharmacokinetics (PKs) in rodent and monkey. Herein, we report a comprehensive summary of studies establishing the pharmaceutical profile of DS‐1211. In vitro studies characterized the mode of inhibition and inhibitory effects of DS‐1211 on three human alkaline phosphatase (ALP) isozymes—TNAP, human intestinal ALP, human placental ALP—and on ALP activity across species in mouse, monkey, and human plasma. In vivo PK and pharmacodynamic (PD) effects of a single oral dose of DS‐1211 in mice and monkeys were evaluated, including biomarker changes in PPi and pyridoxal 5′‐phosphate (PLP). Oral bioavailability (BA) was determined through administration of DS‐1211 at a 0.3‐mg/kg dose in monkeys. In vitro experiments demonstrated DS‐1211 inhibited ALP activity through an uncompetitive mode of action. DS‐1211 exhibited TNAP selectivity and potent inhibition of TNAP across species. In vivo studies in mice and monkeys after single oral administration of DS‐1211 showed linear PKs, with dose‐dependent inhibition of ALP activity and increases in plasma PPi and PLP. Inhibitory effects of DS‐1211 were consistent in both mouse and monkey. Mean absolute oral BA was 73.9%. Overall, in vitro and in vivo studies showed DS‐1211 is a potent and selective TNAP inhibitor across species. Further in vivo pharmacology studies in ectopic calcification animal models and clinical investigations of DS‐1211 in patient populations are warranted. © 2022 Daiichi Sankyo, Inc. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The determination of pyrophosphate and alkaline phosphatase activity plays a significant role in medical diagnosis. In this work, a label-free "ON-OFF-ON" fluorescence strategy is developed for the analysis of pyrophosphate and alkaline phosphatase activity. Using PolyT single strand DNA as templates to synthesize fluorescent copper nanoparticles, the coordination effect of pyrophosphoric acid on Cu2+ inhibited the generation of fluorescence. Afterwards, the addition of alkaline phosphatase into hydrolyze pyrophosphoric acid resulted in the release of Cu2+, whereby the fluorescence intensity could be recovered. Thereupon enhanced-sensitivity for alkaline phosphatase was obtained (0.1 mU/L), much better than previously reported methods. Meanwhile, it could be performed directly in homogeneous solution, which was very close to the actual activity level of alkaline phosphatase under physiological conditions. Likewise, satisfactory results were also obtained in specificity assessment, which demonstrated its potential application in clinical diagnosis. Notably, a new, sensitive, low-cost, short-time, and high-sensitivity platform for alkaline phosphatase detection was constructed, and the design of biosensor using DNA-templated Copper nanoclusters (CuNCs) was instructed in this study. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE) is a genetic multisystem ectopic calcification disorder caused by inactivating mutations in the ABCC6 gene encoding ABCC6, a hepatic efflux transporter. ABCC6-mediated ATP secretion by the liver is the main source of a potent endogenous calcification inhibitor, plasma inorganic pyrophosphate (PPi); the deficiency of plasma PPi underpins PXE. Recent studies demonstrated that INZ-701, a recombinant human ENPP1 that generates PPi and is now in clinical trials, restored plasma PPi levels and prevented ectopic calcification in the muzzle skin of Abcc6 -/- mice. This study examined the pharmacokinetics, pharmacodynamics, and potency of a new ENPP1-Fc isoform, BL-1118, in Abcc6 -/- mice. When Abcc6 -/- mice received a single subcutaneous injection of BL-1118 at 0.25, 0.5, or 1 mg/kg, they had dose-dependent elevations in plasma ENPP1 enzyme activity and PPi levels, with an enzyme half-life of approximately 100 h. When Abcc6 -/- mice were injected weekly from 5 to 15 weeks of age, BL-1118 dose-dependently increased steady-state plasma ENPP1 activity and PPi levels and significantly reduced ectopic calcification in the muzzle skin and kidneys. These results suggest that BL-1118 is a promising second generation enzyme therapy for PXE, the first generation of which is currently in clinical testing., Competing Interests: Declaration of interests D.T.B. and P.R.S. are inventors on patents owned by Yale University for therapeutics treating ENPP1 deficiency. D.T.B. is an equity holder and receives research and consulting support from Inozyme Pharma, Inc., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Pseudo-gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di-cationic calcium ions with tetra-anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra-anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra-cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo-gout., (© 2024 Wiley-VCH GmbH.)

Context: Causative factors for ectopic ossifications in X-linked hypophosphatemia (XLH) remain to be elucidated., Objective: This work aimed to investigate the genotype-phenotype correlations between the phosphate-regulating endopeptidase homologue, X-linked gene ( PHEX ) and ectopic ossifications in XLH., Methods: Biochemical data, spinal computed tomography scans, and x-rays of hip/knee joints were retrospectively reviewed. Genetic analysis and the measurement of plasma inorganic pyrophosphate (PP i )-a potent inhibitor of tissue calcification-were performed. The effect of PHEX mutations on protein function was predicted using nonsense-mediated decay (NMD) and 3-dimensional structure modeling. The index of ossification of the anterior/posterior longitudinal ligament and yellow ligament (OA/OP/OY index) and the sum of the OA/OP/OY index (OS index) were used to quantify the severity of spinal ligament ossification. The severity of the hip/knee osteoarthritis was evaluated by the Kellgren-Lawrence classification., Results: We examined 24 distinct pathogenic PHEX variants in 28 patients from a study population of 33 individuals in 27 unrelated, nonconsanguineous families. Among the 31 patients whose plasma samples were analyzed for PP i , 14 patients (45%) showed decreased plasma PP i concentrations; however, PP i concentrations did not correlate with mutation type or ectopic ossification. Fibroblast growth factor 23 levels in women with NMD-insensitive mutations trended lower than in men with NMD-sensitive mutations but failed to reach statistical significance. Both models revealed no correlations between PHEX pathogenic variant and ectopic ossification., Conclusion: Neither modeling found correlates between PHEX pathogenic variants and ectopic ossification. The effects of PP i on ectopic ossifications in adults with XLH revealed trends that should be investigated with a large sample size., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Much effort is made to achieve the negative thermal expansion (NTE) control, but rare methods reached the improvement of intrinsic NTE. In the present work, a significantly enhanced NTE is realized in Cu 2 P 2 O 7 by applying low pressure. Especially, the volumetric coefficient of thermal expansion (CTE) of Cu 2 P 2 O 7 reached to -50.0 × 10 -6 K -1 (150-325K) under 0.25 GPa, which is increased by 47.5% compared to its NTE in a similar temperature range under atmosphere pressure. This character enables a more effective manifestation of the thermal compensation role of Cu 2 P 2 O 7 in composites. The enhanced NTE mechanisms are analyzed by high pressure synchrotron X-ray diffraction, neutron diffraction at variable temperature and pressure, as well as density functional theory (DFT) calculations. The results show that applied pressure accelerates the contraction of the distance between adjacent CuO layers and CuO columns. Meanwhile, the low-frequency phonon contribution to NTE in α-Cu 2 P 2 O 7 is improved. This work is meaningful for the exploration of methods to enhance NTE and the practical application of NTE materials., (© 2024 Wiley‐VCH GmbH.)

Acetivibrio thermocellus (formerly Clostridium thermocellum) is a potential platform for lignocellulosic ethanol production. Its industrial application is hampered by low product titres, resulting from a low thermodynamic driving force of its central metabolism. It possesses both a functional ATP- and a functional PP i -dependent 6-phosphofructokinase (PP i -Pfk), of which only the latter is held responsible for the low driving force. Here we show that, following the replacement of PP i -Pfk by cytosolic pyrophosphatase and transaldolase, the native ATP-Pfk is able to carry the full glycolytic flux. Interestingly, the barely-detectable in vitro ATP-Pfk activities are only a fraction of what would be required, indicating its contribution to glycolysis has consistently been underestimated. A kinetic model demonstrated that the strong inhibition of ATP-Pfk by PP i can prevent futile cycling that would arise when both enzymes are active simultaneously. As such, there seems to be no need for a long-sought-after PP i -generating mechanism to drive glycolysis, as PP i -Pfk can simply use whatever PP i is available, and ATP-Pfk complements the rest of the PFK-flux. Laboratory evolution of the ΔPP i -Pfk strain, unable to valorize PP i , resulted in a mutation in the GreA transcription elongation factor. This mutation likely results in reduced RNA-turnover, hinting at transcription as a significant (and underestimated) source of anabolic PP i . Together with other mutations, this resulted in an A. thermocellus strain with the hitherto highest biomass-specific cellobiose uptake rate of 2.2 g/g x /h. These findings are both relevant for fundamental insight into dual ATP/PP i Pfk-nodes, which are not uncommon in other microorganisms, as well as for further engineering of A. thermocellus for consolidated bioprocessing., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The increased use of silica and silicon-containing nanoparticles (Si-NP) in agricultural applications has stimulated interest in determining their potential migration in the environment and their uptake by living organisms. Understanding the fate and behavior of Si-NPs will require their accurate analysis and characterization in very complex environmental matrices. In this study, we investigated Si-NP analysis in soil using single-particle ICP-MS. A magnetic sector instrument was operated at medium resolution to overcome the impact of polyatomic interferences (e.g., 14N14N and 12C16O) on 28Si determinations. Consequently, a size detection limit of 29 ± 3 nm (diameter of spherical SiO2 NP) was achieved in Milli-Q water. Si-NP were extracted from agricultural soil using several extractants, including Ca(NO3)2, Mg(NO3)2, BaCl2, NaNO3, Na4P2O7, fulvic acid (FA) and Na2H2EDTA. The best extraction efficiency was found for Na4P2O7, for which the size distribution of Si-NP in the leachates was well preserved for at least one month. On the other hand, Ca(NO3)2, Mg(NO3)2 and BaCl2 were relatively less effective and generally led to particle agglomeration. A time-of-flight ICP-MS was also used to examine the nature of the extracted Si-NP on a single-particle basis. Aluminosilicates accounted for the greatest number of extracted NP (~46%), followed by NP where Si was the only detected metal (presumably SiO2, ~30%).

A novel pyrophosphate Na7Ni3Fe(P2O7)4 was synthesized in two distinct forms, single-crystal and powder. Single-crystal X-ray diffraction was used to determine the crystal structure, and powder X-ray diffraction and scanning electron microscopy were used to examine the purity and morphology of the elaborated powder. This phosphate crystallizes in the P1¯ space group of the triclinic system with a = 6.3677 (2) Å, b = 9.3316 (4) Å, c = 10.8478 (4) Å, α = 65.191 (1)°, β = 80.533 (1)° and γ = 73.042 (1)°. The crystal framework is assembled from the linkage of centro-symmetrical clusters Ni2(Ni/Fe)2P4O28. Each cluster consists of two (Fe1/Ni1)O6 octahedra, two Ni2O6 octahedra and two P2O7 units. The linkage of these clusters is provided by two other P2O7 units to generate a three-dimensional structure with distinct tunnels in the [100], [010] and [001] directions, housing the Na+ cations. The infrared and Raman analyses show the characteristic bands of the pyrophosphate anion P2O74−. Remarkably, the magnetic investigations revealed the coexistence of two magnetic transitions at ~29 K and ~4.5 K with dominating antiferromagnetic interactions.

Membrane pyrophosphatases (mPPases) found in plant vacuoles and some prokaryotes and protists are ancient cation pumps that couple pyrophosphate hydrolysis with the H+ and/or Na+ transport out of the cytoplasm. Because this function is reversible, mPPases play a role in maintaining the level of cytoplasmic pyrophosphate, a known regulator of numerous metabolic reactions. mPPases arouse interest because they are among the simplest membrane transporters and have no homologs among known ion pumps. Detailed phylogenetic studies have revealed various subtypes of mPPases and suggested their roles in the evolution of the "sodium" and "proton" bioenergetics. This treatise focuses on the mechanistic aspects of the transport reaction, namely, the coupling step, the role of the chemically produced proton, subunit cooperation, and the relationship between the proton and sodium ion transport. The available data identify H+-PPases as the first non-oxidoreductase pump with a "direct-coupling" mechanism, i.e., the transported proton is produced in the coupled chemical reaction. They also support a "billiard" hypothesis, which unifies the H+ and Na+ transport mechanisms in mPPase and, probably, other transporters. [ABSTRACT FROM AUTHOR]

[Display omitted] Calciprotein particles (CPPs) are endogenous nanoparticles consisting of hybrid mineral-organic colloidal complexes made of calcium phosphates and Fetuin-A (Fet-A), a protein that in physiological conditions binds to amorphous calcium phosphate forming primary CPP (CPP1). CPP1 can crystallize resulting in hydroxyapatite-based secondary CPP (CPP2) that can eventually precipitate leading to vascular calcifications. The treatment of patients with molecules and ions that delay the amorphous-to-crystalline transition has shown promising results from a clinical perspective, but the study of their mechanism of action has not been thoroughly examined so far. This work describes the formation and crystallization mechanism of synthetic analogs of endogenous CPPs. The effect of different concentrations of Fet-A and of stabilizing agents (Mg2+, citrate and pyrophosphate) on the features and stability of CPPs was addressed by combining different characterization techniques such as turbidimetry, dynamic light scattering, infrared spectroscopy, and scanning electron microscopy. The results show that the stabilizing agents display different action mechanisms and are effective to a different extent in preventing the formation of CPPs or delaying their crystallization. Such findings could be of interest to develop effective therapies for vascular calcifications and to deepen the understanding of amorphous calcium phosphate stabilization and its interaction with proteins. [ABSTRACT FROM AUTHOR]

In this paper, we report a molecular diagnostic system—combining a colorimetric probe (RHthio-CuSO4) for pyrophosphate sensing and isothermal gene amplification (ramified rolling circle amplification)—that operates with high selectivity and sensitivity for clinical point-of-care diagnosis of SARS-CoV-2. During the polymerase phase of the DNA amplification process, pyrophosphate was released from the nucleotide triphosphate as a side product, which was then sensed by our RHthio-CuSO4 probe with a visible color change. This simple colorimetric diagnostic system allowed highly sensitive (1.13 copies/reaction) detection of clinical SARS-CoV-2 within 1 h, while also displaying high selectivity, as evidenced by its discrimination of two respiratory viral genomes (human rhino virus and respiratory syncytial virus) from that of SARS-CoV-2. All of the reactions in this system were performed at a single temperature, with positive identification being made by the naked eye, without requiring any instrumentation. The high sensitivity and selectivity, short detection time (1 h), simple treatment (one-pot reaction), isothermal amplification, and colorimetric detection together satisfy the requirements for clinical point-of-care detection of SARS-CoV-2. Therefore, we believe that this combination of a colorimetric probe and isothermal amplification will be useful for point-of-care testing to prevent the propagation of COVID-19. [ABSTRACT FROM AUTHOR]

Because of growing demands for thermal expansion control in a local region, typically inner components of electronic devices, there is currently a great deal of interest in negative thermal expansion (NTE) fine particles. The spray-drying method without grinding produced micrometer-scale fine particles of pyrovanadate Cu1.8Zn0.2V2O7 showing a large negative coefficient of linear thermal expansion αL ~ –14 ppm/K equivalent to that of the bulk body. The solid-solution system Cu1.8Zn0.2V2–xPxO7 maintains the NTE functionality in a wide x compositional range. Phosphorus substitution contributes to cost reduction and to improvement of electrical insulation. Control of the structural phase transition in the phosphate analog Zn2P2O7 by substituting Mg for Zn realized a huge negative αL exceeding –60 ppm/K over a wide temperature range including room temperature. Because small particles are obtainable even with the conventional solid-phase reaction, the 1 μm level fine particles were obtained successfully using the pulverization method without degrading the function. It has high practicality because it is composed only of inexpensive and environmentally friendly elements such as Zn, Mg, and P. These NTE fine particles are expected to support great progress in thermal expansion control engineering. [ABSTRACT FROM AUTHOR]

Background: Bone scintigraphy is a main diagnostic tool in suspected ATTR patients. Almost all literature is based on conventional whole body gamma cameras, and there is very sparse data evaluating the use of dedicated cardiac CZT cameras. The aim of this study was to evaluate the utility of bone scintigraphy in suspected transthyretin cardiac amyloidosis (ATTR-CA) patients on a dedicated cardiac CZT camera. Methods: Seventy-three patients with suspected ATTR-CA underwent planar and SPECT Tc-99 m pyrophosphate scintigraphy using dedicated cardiac CZT camera between May and August 2019. Results: Planar D-SPECT image quality was mostly good. Six patients were identified as ATTR-CA positive. Inter-observer agreement based on both Perugini score and on planar D-SPECT H/CL ratio was excellent. Conclusions: ATTR-CA scintigraphy using dedicated cardiac CZT camera was feasible, and yielded planar D-SPECT images with excellent inter-observer agreement. [ABSTRACT FROM AUTHOR]

In the present study, pyrophosphate (PP) was used to activate peroxymonosulfate (PMS) for acid orange 7 (AO7) removal under neutral pH conditions. The removal rate of AO7 (20 mg/L) was 84% within the reaction time with a rate constant value of 0.0165 min−1 under optimum conditions. Additionally, the effects of the concentrations of PMS and PP in solutions with various pH values and the coexisting inorganic anions on AO7 removal were measured. In addition, the performance of phosphate (P(V)) on PMS activation was compared with that of phosphite (P(III)) species. In contrast to P(III), the concentration of P(V) showed a positive correlation with the efficiency of AO7 decolorization. PMS activation in different types of buffer solutions was also examined, and the results indicated that the decolorization efficiency of AO7 induced by PP addition, and the buffer solution also contributed to PMS self-decomposition. Singlet oxygen (1O2) might be the primary reactive oxygen species (ROS) in the PP/PMS system in which AO7 is decolorized at an initial pH of 7.06, as indicated by quenching experiments and electron spin resonance (ESR) tests. Therefore, PP/PMS systems may be promising technologies for removing organic contaminants, particularly for PP-rich electroplating wastewater. [ABSTRACT FROM AUTHOR]

Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters. [ABSTRACT FROM AUTHOR]

Amorphous calcium phosphate powders stabilized by crystallization inhibitors based on carboxylate and phosphate salts have been obtained by precipitation from solutions at 10 and 25°C. The presence of inhibitors leads to dispersed precipitates especially for samples with and (the size of primary agglomerates is 300–400 nm); the high values of ζ potential for particles in , and suspensions (<–20 mV) indicate the sufficient aggregative stability of such suspensions. Practical interest in the context of the use of amorphous phosphate powders for production of bioceramics and composites by stereolithographic 3D printing is attracted to phosphates obtained in the presence of trimeta- and tripolyphosphates, inhibitors studied in this work for the first time. [ABSTRACT FROM AUTHOR]

• Matte black alloy film was made by simple multi-zone current density electrodeposition method. • The film has a high vertical light absorption of more than 96% in visible range. • The relationship between the surface morphology of alloy films and its coating process and parameters was investigated. • The distribution of the concentration of metal elements in the film layer along the thickness direction was analyzed. Black films have low reflectance or high absorptivity of light and can be used in a variety of optical applications. Tin-nickel alloys are commonly used to make black films, but both absorptivity coefficient and synthesis process need improvements for real applications. In this study, we prepared a uniform matte black thin film of Sn-Ni alloy by pyrophosphate electrodeposition, and investigate the effects of anode and cathode parameters, current density, anode and cathode distance, plating temperature, and pH and concentration of the plating solution on the absorptivity of the coating in visible range. Optimal process parameters were obtained by orthogonal experiment design and Hull Cell tests, and the resultant thin film has a high vertical absorptivity of 96.7% in the visible range. The experimental result shows that the most effective parameter for electrodeposition is the multi-zone current density regulation. Additives in the plating bath are also important factors, whereas micro-etching can be skipped without apparent degradation in light absorptivity of the deposited film in the visible range. [ABSTRACT FROM AUTHOR]

[Display omitted] • An aggregation-induced emission (AIE)-based strategy is proposed for immunoassay. • Metal-organic framework (MOF) is used to load enzyme and sequester pyrophosphate. • MOF is modified with recombinant target and enzyme by metal coordination interaction. • Dual signal amplification is achieved by enzyme hydrolysis and metal complexation. • Natural, inexpensive, and structurally-simple pyrophosphate is used as the substrate. An aggregation-induced emission (AIE)-based strategy was proposed for fluorescence immunoassays of protein biomarkers using Cu-based metal–organic frameworks (Cu-MOFs) to load recombinant targets and enzymes for dual signal amplification. The immunosensing platform was built based on the sequestration and consumption of the substrates of pyrophosphate (PPi) ions by Cu-MOFs and enzymatic catalysis. The negatively charged PPi could trigger the aggregation of positively charged tetraphenylethene (TPE)-substituted pyridinium salt nanoparticles (TPE-Py NPs) by electrostatic interactions, lighting up the fluorescence due to the AIE phenomenon. The consumption of PPi by the captured Cu-MOFs through the Cu2+-PPi chelation interaction and ALP–enzymatic hydrolysis depressed the aggregation of TPE-Py NPs. Capture of the tested targets in samples by the antibodies on the plate surface could prevent the attachment of target/ALP-loaded Cu-MOFs due to the competitive immunoreactions. The "signal-on" competitive immunoassay was applied for the detection of procalcitonin (PCT) as the model analyte with a linear range of 0.01–10 pg/mL and a detection limit down to 8 pg/mL. The conceptual integration of AIE with enzymatic and MOFs–based dual signal amplification endowed fluorescence immunoassays with high sensitivity and selectivity. The surface modification of Cu-MOFs with hexahistine (His 6)-tagged recombinant proteins through metal coordination interactions should be evaluable for the design of novel biosensors. [ABSTRACT FROM AUTHOR]

Abstract Objective To assess the effects for controlling extrinsic tooth stain of a whitening toothpaste containing 10% high cleaning silica, 0.5% sodium phytate and 0.5% sodium pyrophosphate, in comparison with a negative control toothpaste. Methods A total of 86 adults who met with the inclusion and exclusion criteria were invited to take part in the study. They were distributed into test and control groups randomly. At baseline, 4 weeks and 8 weeks, the same examiner provided the clinical examinations, including evaluations of oral soft and hard tissues and measurements of tooth stain of the anterior teeth using the Lobene Stain Index. Adverse events and any changes in general health conditions of the patients were monitored. Results When the study was completed, comparisons between patients in test and control groups yielded statistically significant differences in Lobene stain adjusted mean area score [0.83 (0.05) vs. 1.13 (0.05)], Lobene stain adjusted mean intensity score [0.99 (0.06) vs. 1.32 (0.06)] and Lobene stain adjusted mean composite score [1.45 (0.13) vs. 2.50 (0.13)] (All, P

The disruption of casein micelles through the addition of calcium sequestering salts (CSS) disodium phosphate (DSP), disodium pyrophosphate (DSPP) and tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP), sodium hexametaphosphate (SHMP) and trisodium citrate (TSC) at 10, 15, 20 and 30 mEq/L levels was investigated in 5% micellar casein isolate (MCI) solution. All the CSS, except DSPP and TSPP, showed a decrease in particle size and viscosity with increasing concentration. The addition of 10–30 mEq/L of CSS to MCI decreased the protein-bound sedimentable Ca and P at pH 6.5 10 kDa-permeable Ca decreased with increasing concentration of DSP, DSPP, TSPP, STPP and SHMP. These results indicate that orthophosphates, pyrophosphates and polyphosphates combined with Ca to form insoluble Ca phosphate complexes together with casein. Higher amount of 10 kDa permeable Ca for MCI samples with TSC confirms the formation of soluble Ca-citrate complexes. [Display omitted] • Phosphate- and citrate-based calcium chelating salts can disrupt casein micelles. • Only citrate-based calcium chelating salts sequested micellar calcium. • Phosphate-based calcium sequestering salts can cause peptization of calcium phosphate nanoclusters. • Hexametaphosphate can interact directly with caseins. [ABSTRACT FROM AUTHOR]

Manganese minerals are ubiquitous in aquatic environments, where both inorganic and organic components can form complexes with them, thereby impacting the release of reactive Mn(III) and the fate of pollutants. The available information about these processes remains insufficient, however, impeding the study of the migration and transformation of pollutants in the environment. In this study, pyrophosphate and humic acid were selected as inorganic and organic ligands typical of aquatic environments, and their impacts on the degradation of Bisphenol A by the β- and δ- variants of MnO 2 were investigated. The results indicate that 1.0–5.0 mM pyrophosphate promotes the generation of reactive Mn(III) from β-MnO 2 , resulting in enhanced degradation of Bisphenol A. Pyrophosphate inhibits δ-MnO 2 -mediated degradation of Bisphenol A due to competition for reactive sites. Humic acids increase the degradation of Bisphenol A mediated by δ-MnO 2 by forming complexes with reactive Mn(III) released from the δ-MnO 2. The degradation of Bisphenol A mediated by minerals in the presence of ligands occurs primarily through hydroxylation, one-electron transfer, and free radical coupling. These findings provide new insights into the role of ligands in the reductive dissolution of manganese minerals and their synergistic effect on the fate of Bisphenol A in aqueous environments. [Display omitted] • Pyrophosphate facilitates the degradation of BPA in the presence of β-MnO 2. • δ-MnO 2 -mediated degradation of BPA is enhanced by HA. • δ-MnO 2 can directly degrade BPA while β-MnO 2 relies on the presence of ligands. • Possible pathways for BPA degradation mediated by β-MnO 2 and δ-MnO 2 are proposed. [ABSTRACT FROM AUTHOR]

• A new anthraquinone-based fluorescent probe HBD was designed and synthesized. • An innovation strategy to sensing Al3+ based on cleaving the −C=N bond was reported. • The plausible binding mechanism was recognized by experimentally and theoretically. • HBD was employed for imaging the Al3+ and PPi in living cells and zebrafish. Anions are widely found in humans and the environment. The analysis of its content and distribution shows great potential in the fields of life science, environmental science and biochemical reactions. Herein, a new anthraquinone derivative appended fluorescent probe (HBD) was developed as a reversible fluorescent probe for the detection pyrophosphate (PPi) in methanol/urotropine buffer medium (1:1, v/v, pH 4.5). The probe displayed fluorescence "turn-on" response towards Al3+ with high specificity. Due to the cleaving of the -C N bond and subsequent creation of complex caused by coordination with Al3+, the chelation-enhanced fluorescence (CHEF) effect was activated, resulting in a significantly enhancement fluorescence response. Further, 1H NMR titration and HRMS analysis revealed that the Al3+ induced hydrolysis occurs on one side of the Schiff base and led to the formation of free primary amine compound. Moreover, the binding mechanism was also recognized density functional theory (DFT) studies. Due to the strong binding ability of PPi and Al3+, PPi could remove Al3+ from the complex, causing fluorescence quenching. The specific determination of Al3+ and PPi with the detecting limit of 31.6 nM and 56.8 nM. Due to its good biocompatibility, the sensor was successfully applied to fluorescence imaging of Al3+ and PPi in HeLa cells and zebrafish. The results show that HBD has broad application prospects in environmental and biological analysis. Anthraquinone-based high selective fluorescent sensor for detection of PPi via an Al3+ disaplacement approach in living cells and zebrafish was reported [Display omitted] [ABSTRACT FROM AUTHOR]

Fenton chemistry has aroused widespread concern due to its application in the green oxidation and mineralization of organic wastes. Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate ions (PPi) and provides a thermodynamic driving force for many biosynthetic reactions. Fluoride (F−) is widely applied to fight against tooth decay and reduce cavities. The electrochemical determination of PPase activity and F− was realized based on Fenton chemistry in this work. Glassy carbon electrode modified with poly (azure A) and acetylene black (GCE/PAA-AB) was fabricated. Hydroxyl radicals (∙OH) that were generated from a Cu2+-catalyzed Fenton-type reaction could oxidize PAA in the near-neutral medium, leading to a great increase of the cathodic peak current (I pc). A coordination reaction between PPi and Cu2+ exerted a negative effect on Fenton reaction and hindered the I pc enhancement. Cu2+-PPi complex was decomposed due to the hydrolysis of PPi induced by PPase, which caused the reappearance of the notably increased current response. F− could effectively inhibit PPase activity. As a result, the stable Cu2+-PPi complex remained and the high I pc suffered from the decline again. The I pc difference was used for the highly sensitive determination of PPase activity in the content range of 0.001–20 mU mL−1 with a detection of limit (LOD) at 0.6 μU mL−1 and that of F− in the concentration range of 0.01–100 μM with a LOD at 7 nM. The proposed PPase and F− sensor displayed a good selectivity, stability and reproducibility, and a high accuracy. [Display omitted] • GCE/PAA-AB was fabricated via a one-pot and two-step method. • PPi, PPase and F− affected the amount of free Cu2+. • Generation, inhibition, recovery and re-inhibition of a Fenton-type reaction appeared. • Peak current during CV scan of GCE/PAA-AB changed repeatedly. • Sensitive detection of PPase activity and F− using the I pc difference was realized. [ABSTRACT FROM AUTHOR]

• The phonon anomalies in Zn 2 P 2 O 7 during the α - to β -phase transition have been unveiled. • The specific bond lengths, bond angles, and polyhedral distortion indices are confirmed to induce the phonon anomalies. • The negative Grüneisen parameter γ i in the α -phase explains the lower thermal expansion compared to that of the β -phase. Zn 2 P 2 O 7 , a representative material in the A 2 P 2 O 7 family, exhibits negative thermal expansion (NTE) and possesses a remarkable negative linear expansion coefficient. Here we employ variable temperature and high-pressure Raman spectroscopy to investigate the phonon anomalies arising from the α - to β -phase transition in Zn 2 P 2 O 7. Combing with the refinement results of our X-ray diffraction (XRD) experiment, we have identified the specific variations of the bond lengths, bond angles and the polyhedral distortion indexes that result in the phonon anomalies. Some certain phonons, whose energy decreases with increasing pressure, have been demonstrated to give rise to negative Grüneisen parameters that can characterize phonon anharmonicity and lead to lower thermal expansion in the α -phase of Zn 2 P 2 O 7 compared to the β -phase. These results provide new insight into the relationship between lattice deformation and phonon anomalies during the structural phase transition in the NTE material Zn 2 P 2 O 7. [ABSTRACT FROM AUTHOR]

A novel naphthalimides‐based fluorescent probe (NPHD) selectively detected Cu2+ and PPi through "strong yellow‐weak green‐strong yellow" photonic response in a sequential manner. The formation of NPHD‐Cu2+ resulted in obvious fluorescence decreased and wavelength shift from 595 nm to 525 nm by adding Cu2+ to NPHD solution. The mechanism could be attributed to d→π* electron transfer (ET) from Cu2+ to NPHD. Furthermore, the NPHD‐Cu2+ complex exhibited high selectivity toward PPi through via emission recovery of chemosensor NPHD. The detection limits of NPHD to Cu2+ and NPHD‐Cu2+ to PPi were estimated to be 5.72×108M and 2.39×108M. In addition, NPHD could be employed to detect exogenous Cu2+ and PPi in Hep G2 cells. [ABSTRACT FROM AUTHOR]

The plasma membrane protein ankylosis homologue (ANKH, mouse ortholog: Ank) prevents pathological mineralization of joints by controlling extracellular levels of the mineralization inhibitor pyrophosphate (PPi). It was long thought that ANKH acts by transporting PPi into the joints. We recently showed that when overproduced in HEK293 cells, ANKH mediates release of large amounts of nucleoside triphosphates (NTPs), predominantly ATP, into the culture medium. ATP is converted extracellularly into PPi and AMP by the ectoenzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). We could not rule out, however, that cells also release PPi directly via ANKH. We now addressed the question of whether PPi leaves cells via ANKH using HEK293 cells that completely lack ENPP1. Introduction of ANKH in these ENPP1‐deficient HEK293 cells resulted in robust cellular ATP release without the concomitant increase in extracellular PPi found in ENPP1‐proficient cells. Ank activity was previously shown to be responsible for about 75% of the PPi found in mouse bones. However, bones of Enpp1−/− mice contained <2.5% of the PPi found in bones of wild‐type mice, showing that Enpp1 activity is also a prerequisite for Ank‐dependent PPi incorporation into the mineralized bone matrix in vivo. Hence, ATP release precedes ENPP1‐mediated PPi formation. We find that ANKH also provides about 25% of plasma PPi, whereas we have previously shown that 60% to 70% of plasma PPi is derived from the NTPs extruded by the ABC transporter, ABCC6. Both transporters that keep plasma PPi at sufficient levels to prevent pathological calcification therefore do so by extruding NTPs rather than PPi itself. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE; OMIM 264800) is a rare heritable multisystem disorder, characterized by ectopic mineralization affecting elastic fibres in the skin, eyes and the cardiovascular system. Skin findings often lead to early diagnosis of PXE, but currently, no specific treatment exists to counteract the progression of symptoms. PXE belongs to a group of Mendelian calcification disorders linked to pyrophosphate metabolism, which also includes generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC). Inactivating mutations in ABCC6, ENPP1 and NT5E are the genetic cause of these diseases, respectively, and all of them result in reduced inorganic pyrophosphate (PPi) concentration in the circulation. Although PPi is a strong inhibitor of ectopic calcification, oral supplementation therapy was initially not considered because of its low bioavailability. Our earlier work however demonstrated that orally administered pyrophosphate inhibits ectopic calcification in the animal models of PXE and GACI, and that orally given Na4P2O7 is absorbed in humans. Here, we report that gelatin‐encapsulated Na2H2P2O7 has similar absorption properties in healthy volunteers and people affected by PXE. The sodium‐free K2H2P2O7 form resulted in similar uptake in healthy volunteers and inhibited calcification in Abcc6−/− mice as effectively as its sodium counterpart. Novel pyrophosphate compounds showing higher bioavailability in mice were also identified. Our results provide an important step towards testing oral PPi in clinical trials in PXE, or potentially any condition accompanied by ectopic calcification including diabetes, chronic kidney disease or ageing. [ABSTRACT FROM AUTHOR]

The aqueous self‐assembly of amphiphiles into aggregates such as micelles and vesicles has been widely investigated over the past decades with applications ranging from materials science to drug delivery. The combination of characteristic properties of nucleic acids and amphiphiles is of substantial interest to mimic biological self‐organization and compartmentalization. Herein, we present ribose‐ and ribonucleotide‐based amphiphiles and investigate their self‐assembly as well as their fundamental reactivity. We found that various types of aggregates are formed, ranging in size from nanometers to micrometers and all amphiphiles exhibit aggregation‐induced emission (AIE) in solution as well as in the solid state. We also observed that the addition of 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC) leads to rapid and selective dimerization of the amphiphiles into pyrophosphates, which decreases the critical aggregation concentration (CAC) by a factor of 25 when compared to the monomers. Since the propensity for amphiphile dimerization is correlated with their tendency to self‐assemble, our results may be relevant for the formation of rudimentary compartments under prebiotic conditions. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis (CA) is the buildup and infiltration of amyloid plaque in cardiac muscle. An underdiagnosed form of restrictive cardiomyopathy, CA can rapidly progress into heart failure. CA is evaluated using a multimodality approach that includes echocardiography, cardiac magnetic imaging, and nuclear imaging. Echocardiography remains an essential first-line modality that raises suspicion for CA and establishes functional baselines. Cardiac magnetic imaging provides additional incremental value via high-resolution imaging, robust functional assessment, and superior tissue characterization, all of which enable a more comprehensive investigation of CA. Cardiac scintigraphy has eliminated the need for invasive diagnostic approaches and helps differentiate CA subtypes. Positron emission tomography is the first modality introducing targeted amyloid binding tracers that allow for precise burden quantification, early detection, and disease monitoring. In this review, we highlight the role of several cardiac imaging techniques in the evaluation of CA. [ABSTRACT FROM AUTHOR]

Negative thermal expansion (NTE) is an intriguing physical phenomenon, which is of great significance for the high precision application. In this work, we have realized to broaden the NTE temperature zone in Mg2P2O7-based bulk material by doping Cu atom on the Mg site. A joint study of Raman scattering and X-ray diffraction (XRD) indicates that there are double phases in the NTE temperature zone, and the NTE of Mg1.9Cu0.1P2O7 bulk material comes from the phase transition of α- and β-phase. The present work provides a way to optimize negative thermal expansion property in phase transition typed materials.

Inclusion bodies are typically ignored as they are considered unwanted protein waste generated by prokaryotic host cells during recombinant protein production or harmful protein inclusions in human cell biology. However, these protein particles may have applications for in vivo immobilization in industrial biocatalysis or as cell-tolerable protein materials for the pharmaceuticals industry and clinical development. Thus, there is a need to in vivo “pull-down” (insolubilize) soluble enzymes and proteins into inclusion bodies. Accordingly, in this study, sequences from the short-chain polyphosphatase ygiF were used to design pull-down tags capable of detecting (poly)-phosphates and metal ions. These tags were compared with the entire CHAD domain from Escherichia coli ygiF and SACS2 CHAD from Saccharolobus solfataricus. The results demonstrated that highly soluble green fluorescent protein variants could be pulled down into the inclusion bodies and could have modified sensitivity to metals and di-/tri-inorganic phosphates.

The atypical glycolysis of Clostridium thermocellum is characterized by the use of pyrophosphate (PPi) as a phosphoryl donor for phosphofructokinase (Pfk) and pyruvate phosphate dikinase (Ppdk) reactions. Previously, biosynthetic PPi was calculated to be stoichiometrically insufficient to drive glycolysis. This study investigates the role of a H1- pumping membrane-bound pyrophosphatase, glycogen cycling, a predicted Ppdk-malate shunt cycle, and acetate cycling in generating PPi. Knockout studies and enzyme assays confirmed that clo1313_0823 encodes a membrane-bound pyrophosphatase. Additionally, clo1313_0717-0718 was confirmed to encode ADP-glucose synthase by knockouts, glycogen measurements in C. thermocellum, and heterologous expression in Escherichia coli. Unexpectedly, individually targeted gene deletions of the four putative PPi sources did not have a significant phenotypic effect. Although combinatorial deletion of all four putative PPi sources reduced the growth rate by 22% (0.30±0.01 h21) and the biomass yield by 38% (0.18±0.00 gbiomass gsubstrate 21), this change was much smaller than what would be expected for stoichiometrically essential PPi-supplying mechanisms. Growth-arrested cells of the quadruple knockout readily fermented cellobiose, indicating that the unknown PPi-supplying mechanisms are independent of biosynthesis. An alternative hypothesis that ATP-dependent Pfk activity circumvents a need for PPi altogether was falsified by enzyme assays, heterologous expression of candidate genes, and whole-genome sequencing. As a secondary outcome, enzymatic assays confirmed functional annotation of clo1313_1832 as ATP- and GTP-dependent fructokinase. These results indicate that the four investigated PPi sources individually and combined play no significant PPi-supplying role, and the true source(s) of PPi, or alternative phosphorylating mechanisms, that drive(s) glycolysis in C. thermocellum remain(s) elusive. [ABSTRACT FROM AUTHOR]

The pyrophosphate mimicking groups offer rational modification of the pyrophosphate‐bearing natural substrates of the overexpressed enzymes that cause the onset of disease progression. Mainly, the modified substrate interacts differently with the enzyme active site eventually causing its deactivation, or provides the therapeutically active products at the completion of the catalytic cycle that contribute toward the inhibition of the target enzyme. Many of the pyrophosphate mimic‐containing molecules serve as competitive or allosteric inhibitors of the target enzyme to achieve the desirable properties for the mitigation of the target enzyme's pathophysiology. This review presents an epigrammatic overview of the pyrophosphate mimics in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Single crystals of KScP2O7, potassium scandium diphosphate, were grown in a borate flux. The title compound crystallizes isotypically with KAlP2O7 in space-group type P21/c, Z = 4. The main building block is an {ScP2O11}9– unit, forming layers parallel to (001). These layers are stacked along [001] via common corners of octahedral and tetrahedral units to span up large heptagonal cavities that host the potassium cations with a coordination number of 10. The P—O—P bridging angle increases with increasing size of the octahedrally coordinated MIII cation, as do the K—O distances within a series of KMIIIP2O7 compounds (MIII = Al to Y with ionic radii r = 0.538 to 0.90 Å).

Technetium-99m-pyrophosphate (99mTc-PYP) has been used, in combination with thallium-201, to estimate the site and extent of myocardial infarcts. We report a case of acute myocardial infarction with severe coronary disease in which the distribution of 99mTc-PYP was extensive. A 78-year-old man presented with dyspnea, and a diagnosis of non-ST-segment elevation acute myocardial infarction was made. Emergency coronary angiography revealed total occlusion of the proximal portion of the right coronary artery and left circumflex coronary artery with collateral flow from the left anterior descending coronary artery, which also had severe stenoses. Given his comorbidities and preferences, subsequent angioplasty was waived. Dual myocardial scintigraphic imaging, which was performed four days after admission, demonstrated slightly reduced thallium-201 uptake in the inferior wall and apex, whereas 99mTc-PYP was positive in the entire left ventricular subendocardial region and the free wall of the right ventricle. His clinical course was uneventful with conservative treatment and the patient was discharged 20 days after admission in a stable condition.

The power of sensing molecules is often characterized in part by determining their thermodynamic/dynamic properties, in particular the binding constant of a guest to a host. In many studies, traditional nonlinear regression analysis has been used to determine the binding constants, which cannot be applied to complex systems and limits the reliability of such calculations. Supramolecular sensor systems include many interactions that make such chemical systems complicated. The challenges in creating sensing molecules can be significantly decreased through the availability of detailed mathematical models of such systems. Here, we propose uncovering accurate thermodynamic parameters of chemical reactions using better-defined mathematical modeling-fitting analysis is the key to understanding molecular assemblies and developing new bio/sensing agents. The supramolecular example we chose for this investigation is a self-assembled sensor consists of a synthesized receptor, DPA (DPA = dipicolylamine)-appended phenylboronic acid (1) in combination with Zn2+(1.Zn) that forms various assemblies with a fluorophore like alizarin red S (ARS). The self-assemblies can detect multi-phosphates like pyrophosphate (PPi) in aqueous solutions. We developed a mathematical model for the simultaneous quantitative analysis of twenty-seven intertwined interactions and reactions between the sensor (1.Zn-ARS) and the target (PPi) for the first time, relying on the Newton-Raphson algorithm. Through analyzing simulated potentiometric titration data, we describe the concurrent determination of thermodynamic parameters of the different guest-host bindings. Various values of temperatures, initial concentrations, and starting pHs were considered to predict the required measurement conditions for thermodynamic studies. Accordingly, we determined the species concentrations of different host-guest bindings in a generalized way. This way, the binding capabilities of a set of species can be quantitatively examined to systematically measure the power of the sensing system. This study shows analyzing supramolecular self-assemblies with solid mathematical models has a high potential for a better understanding of molecular interactions within complex chemical networks and developing new sensors with better sensing effects for bio-purposes.

Adenosine diphosphate (ADP)-ribosylation is a ubiquitous post-translational modification that regulates vital biological processes like histone reorganization and DNA-damage repair through the modification of various amino acid residues. Due to advances in mass-spectrometry, the collection of long-known ADP-ribose (ADPr) acceptor sites, e.g. arginine, cysteine and glutamic acid, has been expanded with serine, tyrosine and histidine, among others. Well-defined ADPr-peptides are valuable tools for investigating the exact structures, mechanisms of action and interaction partners of the different flavors of this modification. This review provides a comprehensive overview of synthetic and chemoenzymatic methodologies that enabled the construction of peptides mono-ADP-ribosylated on various amino acids, and close mimetics thereof., (© 2024 Wiley‐VCH GmbH.)

Hypophosphatasia (HPP) is a rare genetic condition associated with poor bone mineralization, low serum alkaline phosphatase, high urinary pyrophosphate excretion, and nephrocalcinosis. Nephrocalcinosis is thought to develop due to the increased filtered loads associated with hypercalcemia and hyperphosphatemia, but the composition of these calcifications is incompletely understood. We report the first ever magnesium pyrophosphate (MgPPi) urinary stone, which prompted the new diagnosis of HPP in a 12-year-old boy. Stone analysis labs should include infrared spectra of PPi salts in their reference libraries to facilitate identification of these rare but clinically important stones., (© 2024 Published by Elsevier Inc.)

Novel sulfur and selenium substituted 5′,5′-linked dinucleoside pyrophate analogues were prepared in a vibration ball mill from the corresponding persilylated monophosphate. The chemical hydrolysis of pyrophosphorochalcogenolate-linked dimers was studied over a wide pH-range. The effect of the chalcogeno-substitution on the reactivity of dinucleoside pyrophosphates was surprisingly modest, and the chemical stability is promising considering the potential therapeutic or diagnostic applications. The chemical stability of the precursor phosphorochalcogenolate monoesters was also investigated. Hydrolytic desilylation of these materials was effected in aqueous buffer at pH 3, 7 or 11 and resulted in phosphorus-chalcogen bond scission which was monitored using 31P NMR. The rate of dephosphorylation was dependent upon both the nature of the chalcogen and the pH. The integrity of the P-S bond in the corresponding phosphorothiolate was maintained at high pH but rapidly degraded at pH 3. In contrast, P-Se bond cleavage of the phosphoroselenolate monoester was rapid and the rate increased with alkalinity. The results obtained in kinetic experiments provide insight on the reactivity of the novel pyrophosphates studied as well as of other types of thiosubstituted biological phosphates. At the same time, these results also provide evidence for possible formation of unexpectedly reactive intermediates as the chalcogen-substituted analogues are metabolised.

Keywords: ABCC6; ageing; bone loss; PXE; pyrophosphate EN ABCC6 ageing bone loss PXE pyrophosphate 1635 1637 3 10/06/22 20221001 NES 221001 ABCC6 transporter deficiency causes pseudoxanthoma elasticum (PXE), a rare disease associated with progressive calcification in the eyes, skin and arteries. This phenotype is essentially characterized by trabecular bone loss and likely linked to an increased osteoclastic activity.3 Our group, using a similar CT-scan approach4 in 2-year-old I Abcc6-/- i mice,5 evidenced a similar bone loss of the tibiae characterized by decreased trabecular bone percentage, trabecular number and increased inter trabecular spacing (see Figure 1). [Extracted from the article]

Background and Objective: Periodontal ligament stem cells (PDLSCs) are the primary cell source for the regeneration and remodeling of periodontal ligament (PDL). It is crucial to prevent PDLSCs from mineralization when using the PDLSCs for PDL regeneration. At present, little is known about how to inhibit PDLSC mineralization. This study investigates the effects of pyrophosphate (PPi) on inhibiting PDLSC osteogenic differentiation and mineralization as well as the underlying mechanism. Materials and Methods: Human PDLSCs were cultured in an osteogenic differentiation medium with different PPi concentrations (0, 10, or 100 μM). The effects of PPi on osteogenic differentiation were assessed by ALP activity and the expressions of osteogenic related proteins (OPN, RUNX2, OSX, and DMP1). The mineralization formation was detected by alizarin red staining. The activation of MAPK signaling pathways (ERK1/2, JNK, and p38) was determined by western blotting and pathway blockade assays. The gene expressions of PPi's regulators (Ank, Enpp1, and Alpl) were assessed by real‐time PCR. Results: Both low and high concentrations (10 μM and 100 μM) of PPi inhibited the mineralization of PDLSCs. The addition of PPi (10 μM or 100 μM) decreased the ALP activity of the PDLSCs to approximately two‐thirds of the control group on day 3. PPi reduced the expressions of RUNX2, OSX, and DMP1 on days 7, 14, and 21, while it increased the expression of OPN at the three time points. PPi enhanced the phosphorylation of MAPK pathways, and the application of corresponding MAPK pathway inhibitors reversed the osteogenic inhibition effects of PPi. Conclusion: PPi inhibits the osteogenic differentiation and mineralization of PDLSCs in vitro through activating ERK1/2, JNK, and p38 signaling pathways. [ABSTRACT FROM AUTHOR]

The present work is the first investigation of the electrocatalytic performances of ZrP2O7 as a cathode in a single-chamber Microbial Fuel Cell (MFC) for the conversion of chemical energy from wastewater to bioelectricity. This catalyst was prepared by a coprecipitation method, then characterized by X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), ultraviolet–visible–near-infrared spectrophotometry (UV–Vis–NIR), and cyclic voltammetry analyses. The acid–basic characteristics of the surface were probed by using 2-butanol decomposition. The conversion of 2-butanol occurs essentially through the dehydrating reaction, indicating the predominantly acidic character of the solid. The electrochemical test shows that the studied cathode material is electroactive. In addition, the ZrP2O7 in the MFC configuration exhibited high performance in terms of bioelectricity generation, giving a maximum output power density of around 449 mW m−2; moreover, it was active for wastewater treatment, reducing the chemical oxygen demand (COD) charge to 50% after three days of reaction.

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