Precursor Phase Research Articles

P-058: The dynamics of nucleotide variants in the progression from myeloma precursor conditions to multiple myeloma using targeted sequencing of serial bone marrow samples

<h3>Background</h3> Multiple myeloma (MM) is known to evolve from the premalignant precursor conditions Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). The exact mechanisms driving this progression are still not completely understood. The continuum between MGUS-SMM-MM provides the opportunity to investigate its evolution. However, collecting paired/serial samples from low and intermediate risk precursors progressing to MM are significantly hindered by the (i) only incidental diagnosis of asymptomatic precursors, (ii) invasive bone marrow (BM) sampling, (iii) very low number of aberrant BM plasma cells (PCs), and (iv) rather irregular disease follow-up. <h3>Methods</h3> In this study, a unique retrospective collection of paired BM samples was available because of an effective biobanking effort. We had access to 68 archival diagnostic May-Grünwald–Giemsa (MGG)-stained BM smears from 21 progressing low to intermediate risk myeloma precursor patients, 19 MGUS and 2 SMM, with a median time to progression of 6 years. DNA was extracted from these BM smears and Next Generation Sequencing (NGS) was performed using a custom targeted capture-based sequencing panel (Illumina) including coding exons or hotspots of 81 selected myeloma-related genes with the aim to study the evolution of single nucleotide variants (SNVs) and short insertions and deletions (indels). The pooled libraries were paired-end sequenced on a MiSeq instrument (Illumina). <h3>Results</h3> Data was analyzed with Local Run Manager and annotated with VariantStudio. After filtering, only exonic nonsynonymous and loss-of-function variants with a coverage >30 and a variant allele frequency (AF) >1% were retrieved. A variant detected in the MM phase but not in the prestage of that patient was manually inspected in the data visualization tool of Integrated Genome Viewer (IGV) to assess its presence. With a mean coverage of 636x of the targeted captured region the sequencing depth was sufficiently high to detect low burden variants down to an AF of 1%. A median of 2 variants per patient (range 0 to 5 with a total of 38 variants) was detected. While in 19 patients at least one variant was detected in the MM phase, in 2 patients not a single variant was detected in any of the 81 genes. Interestingly, the majority of variants in MM could already be detected at low AFs in the BM smears sampled in the precursor phase, even many years before progression. The reason why some variants were not detected in a prestage is likely due to sensitivity issues (BM PCs ≤2.5%). The median time of detection of a variant in the precursor stage BM was 49 months (>4 years; range 10 to 105 months) prior to MM progression. <h3>Conclusion</h3> In conclusion, targeted sequencing of unsorted BM smears from myeloma precursor conditions can already provide relevant insights into the behavior of mutant clones. Paired sample analysis can reveal the genetic architecture of somatic variation in the prestage even with low proliferative PCs in the BM.

Polymer intercalation synthesis of glycoboehmite nanosheets

Novel materials based on the aluminum oxyhydroxide boehmite phase were prepared using a glycothermal reaction in 1,4-butanediol. Under the synthesis conditions, the atomic structure of the boehmite phase is altered by the glycol solvent in place of the interlayer hydroxyl groups, creating glycoboehmite. The structure of glycoboehmite was examined in detail to determine that glycol molecules are intercalated in a bilayer structure, which would suggest that there is twice the expansion identified previously in the literature. This precursor phase enables synthesis of two new phases that incorporate either polyvinylpyrrolidone or hydroxylpropyl cellulose nonionic polymers. These new materials exhibit changes in morphology, thermal properties, and surface chemistry. All the intercalated phases were investigated using PXRD, HRSTEM, SEM, FT-IR, TGA/DSC, zeta potential titrations, and specific surface area measurement. These intercalation polymers are non-ionic and interact through wetting interactions and hydrogen bonding, rather than by chemisorption or chelation with the aluminum ions in the structure.

Nickelate Superconductivity without Rare-Earth Magnetism: (La,Sr)NiO2.

The occurrence of unconventional superconductivity in cuprates has long motivated the search for manifestations in other layered transition metal oxides. Recently, superconductivity is found in infinite-layer nickelate (Nd,Sr)NiO2 and (Pr,Sr)NiO2 thin films, formed by topotactic reduction from the perovskite precursor phase. A topic of much current interest is whether rare-earth moments are essential for superconductivity in this system. In this study, it is found that with significant materials optimization, substantial portions of the La1- x Srx NiO2 phase diagram can enter the regime of coherent low-temperature transport (x= 0.14 - 0.20), with subsequent superconducting transitions and a maximum onset of ≈9 K at x= 0.20. Additionally, the unexpected indication of a superconducting ground state in undoped LaNiO2 is observed, which likely reflects the self-doped nature of the electronic structure. Combining the results of (La/Pr/Nd)1- x Srx NiO2 reveals a generalized superconducting dome, characterized by systematic shifts in the unit cell volume and in the relative electron-hole populations across the lanthanides.

Exploiting Confinement to Study the Crystallization Pathway of Calcium Sulfate

AbstractCharacterizing the pathways by which crystals form remains a significant challenge, particularly when multiple pathways operate simultaneously. Here, an imaging‐based strategy is introduced that exploits confinement effects to track the evolution of a population of crystals in 3D and to characterize crystallization pathways. Focusing on calcium sulfate formation in aqueous solution at room temperature, precipitation is carried out within nanoporous media, which ensures that the crystals are fixed in position and develop slowly. The evolution of their size, shape, and polymorph can then be tracked in situ using synchrotron X‐ray computed tomography and diffraction computed tomography without isolating and potentially altering the crystals. The study shows that bassanite (CaSO4 0.5H2O) forms via an amorphous precursor phase and that it exhibits long‐term stability in these nanoscale pores. Further, the thermodynamically stable phase gypsum (CaSO4 2H2O) can precipitate by different pathways according to the local physical environment. Insight into crystallization in nanoconfinement is also gained, and the crystals are seen to grow throughout the nanoporous network without causing structural damage. This work therefore offers a novel strategy for studying crystallization pathways and demonstrates the significant impact of confinement on calcium sulfate precipitation, which is relevant to its formation in many real‐world environments.

On-site smart biomimetic mineralization of starch-templated CaP prenucleation clusters triggered by α-amylase

With the attention of biomineralization, calcium phosphate precursor phases regulated by different organic templates are synthesized and used as mineral sources for biomimetic mineralization. However, most of the organic templates have limited ability to stabilize calcium and phosphorus ions, or the selected templates have poor biocompatibility and irremovability, which make them difficult to co-exist in long-term stability and crystal transformation, and to achieve convenient and harmless clinical application. Herein, we propose a calcium phosphate prenucleation clusters (CaP-PNCs)/starch complex, which includes uniform-sized, separate, and homogeneously distributed amorphous calcium phosphate nanoclusters of about 1 nm. By means of freeze-drying and redissolution, the CaP-PNCs/starch complex can be converted between liquid and spongy solid without changing their morphology and amorphous phase, and the freeze-dried CaP-PNCs/starch complex can be stored at room temperature for at least 5 months. Imitating the mechanism of protein-protease controlled biomineralization in organisms, the CaP-PNCs/starch complex is mixed with α-amylase during application. Starch templates are removed by enzymolysis and CaP-PNCs can be released, thus triggering on-site biomimetic mineralization with enamel-like structures to repair tooth tissue defects (including enamel and dentin). CaP-PNCs/starch complex provides a smart mineral source supply for biomimetic mineralization and a new pathway for the design of biomimetic materials.

A time-course Raman spectroscopic analysis of spontaneous in vitro microcalcifications in a breast cancer cell line

Microcalcifications are early markers of breast cancer and can provide valuable prognostic information to support clinical decision-making. Current detection of calcifications in breast tissue is based on X-ray mammography, which involves the use of ionizing radiation with potentially detrimental effects, or MRI scans, which have limited spatial resolution. Additionally, these techniques are not capable of discriminating between microcalcifications from benign and malignant lesions. Several studies show that vibrational spectroscopic techniques are capable of discriminating and classifying breast lesions, with a pathology grade based on the chemical composition of the microcalcifications. However, the occurrence of microcalcifications in the breast and the underlying mineralization process are still not fully understood. Using a previously established model of in vitro mineralization, the MDA-MB-231 human breast cancer cell line was induced using two osteogenic agents, inorganic phosphate (Pi) and β-glycerophosphate (βG), and direct monitoring of the mineralization process was conducted using Raman micro-spectroscopy. MDA-MB-231 cells cultured in a medium supplemented with Pi presented more rapid mineralization (by day 3) than cells exposed to βG (by day 11). A redshift of the phosphate stretching peak for cells supplemented with βG revealed the presence of different precursor phases (octacalcium phosphate) during apatite crystal formation. These results demonstrate that Raman micro-spectroscopy is a powerful tool for nondestructive analysis of mineral species and can provide valuable information for evaluating mineralization dynamics and any associated breast cancer progression, if utilized in pathological samples.The mineralization of MDA-MB-231 breast cells was investigated using Raman micro-spectroscopy. Mineralization was induced by two osteogenic agents: inorganic phosphate (Pi) and β-Glycerophosphate (βG). The results show that the uptake of Pi allows a faster mineralization and the uptake of βG indicated the presence of a precursor phase during the hydroxyapatite crystal formation.

Boron isotope fractionation during the formation of amorphous calcium carbonates and their transformation to Mg-calcite and aragonite

The non-classical crystallization pathway of carbonate minerals proceeds through the initial formation of an amorphous precursor phase and commonly takes place during biomineralization. Although the isotopic composition of marine calcifiers is often used to reconstruct paleo-environmental conditions, the impact of the crystallization pathway followed by these organisms on the isotope composition of their skeletons has rarely been quantified. This study presents the first examination of B partitioning and isotope fractionation during CaCO3 formation via an amorphous calcium carbonate phase, which provides new insights into the incorporation of B into marine calcite and aragonite that form via this route. Boron concentrations and isotope compositions of the fluids and the formed solids were characterized during the course of experiments that lasted two years and were performed at 25 °C under controlled pH conditions. The results suggest that during Mg-ACC formation, B distribution coefficients are 1.5–4 orders of magnitude higher than those reported earlier in the literature for calcite and aragonite. Additionally, B isotope fractionation during Mg-ACC formation is strongly affected by the continuous exchange of solutes between the nanoporous solid phase and the bulk fluid. The isotope composition of the transient amorphous phase is not inherited in the crystalline carbonate mineral phase that ultimately forms, because crystallization proceeds via a continuous dissolution/re-precipitation process and/or chemical/isotope exchange between the solid surface and the fluid. Interestingly, the isotope fractionation between the fluid and the final crystalline products is different from those achieved in earlier studies where mineral growth proceeded via the standard mechanism of ion-by-ion addition of solutes to advancing steps. The B isotope fractionations measured in this study are in good agreement with results of equilibrium first principle calculations for calcite and aragonite (Balan et al., 2018) except in the case of calcite formed at pH = 8.9, suggesting that changes in aqueous speciation (i.e. increase of NaB(OH)4° and CO32− concentrations) may be responsible for slight changes of the calcite BO4 environment and isotope composition. It is expected that this study will help to better decipher the mechanisms controlling B isotope fractionation during the non-classical growth of calcium carbonates involving the formation of transient amorphous precursors.

Sodium incorporation into inorganic CaCO3 and implications for biogenic carbonates

The sodium content of biogenic carbonates shows potential as a palaeoceanographic proxy for salinity and/or calcium concentration but the incorporation of Na+ into inorganic and biogenic calcite is poorly understood. Taxonomic and conspecific variations in the sensitivity of carbonate Na/Ca to seawater Na+/Ca2+ and salinity point to a biological influence on Na+ partitioning and/or covariations with other environmental parameters. One major unknown of the biological control during calcification is the rate of mineral precipitation, which has a strong control on trace-element partitioning in inorganic carbonate systems. We conducted inorganic CaCO3 precipitation experiments where the effect of solution composition and crystal growth rate on Na+ uptake by carbonate crystals are independently assessed. Calcite crystals were precipitated at rates varying from 10−6.5 to 10−4.5 mol/m2/s, while faster growth rate than 10−4.5 mol/m2/s resulted in the coprecipitation of aragonite and vaterite. For a given crystal growth rate, calcite Na/Ca increases by 0.22% per % increase in solution (Na+)2/Ca2+ activity ratio. However, calcite Na/Ca increases up to fivefold per order of magnitude increase in crystal growth rate, suggesting crystal growth rate and precursor phases are likely dominant controls on marine carbonate Na/Ca. We use these results in the framework of the DePaolo (2011) model for trace element uptake by calcite to assess the origin of variable (Na/Ca)foraminifer sensitivities to [Ca2+]seawater and salinity. Last, maximum mineral growth rates are estimated for a range of marine carbonates based on known carbonate Na/Ca and the (Na+)2/Ca2+ activity ratio of seawater. Estimated rates vary from 10−5.6 (planktic foraminifers) to above 10−4 (sea urchins) mol/m2/s. Such high mineral growth rates imply high degrees of oversaturation with respect to calcite (10 to >100), supporting the idea that elemental partitioning and isotopic fractionation recorded in marine biogenic carbonates are controlled by kinetic rather than equilibrium exchanges.

Origin of ULVZs near the African LLSVP: Implications from their distribution and characteristics

Ultra-low velocity zones (ULVZs) provide important information on the composition and dynamics of the core-mantle boundary (CMB). However, their global distribution and characteristics are not well constrained, especially near African large low-shear velocity provinces (LLSVPs). Here, we used ScS precursor (SdS) and postcursor (ScscS) phases recorded by various seismic networks in Africa and South America to investigate the ULVZ characteristics underlying the South Atlantic Ocean. We found no evidence of ULVZs near the SE boundary of South America, but an ULVZ was found within the SW boundary of the African LLSVP, with thicknesses ranging from 11–18 km and reductions in S-wave velocities of 18%–34%. Our results, combined with the global distribution of ULVZs, suggest that thermal activity may be essential to ULVZ formation. Moreover, subducted slab and mantle flow may also play a key role, depending on the location of the ULVZs.

Sol-Gel Synthesis of the Double Perovskite Sr2FeMoO6 by Microwave Technique.

The effect of microwave radiation on the hydrothermal synthesis of the double perovskite Sr2FeMoO6 has been studied based on a comparison of the particle size and structural characteristics of products from both methods. A temperature, pressure, and pH condition screening was performed, and the most representative results of these are herein presented and discussed. Radiation of microwaves in the hydrothermal synthesis method led to a decrease in crystallite size, which is an effect from the reaction temperature. The particle size ranged from 378 to 318 nm when pH was 4.5 and pressure was kept under 40 bars. According to X-ray diffraction (XRD) results coupled with the size-strain plot method, the product obtained by both synthesis methods (with and without microwave radiation) have similar crystal purity. The Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) techniques showed that the morphology and the distribution of metal ions are uniform. The Curie temperature obtained by thermogravimetric analysis indicates that, in the presence of microwaves, the value was higher with respect to traditional synthesis from 335 K to 342.5 K. Consequently, microwave radiation enhances the diffusion and nucleation process of ionic precursors during the synthesis, which promotes a uniform heating in the reaction mixture leading to a reduction in the particle size, but keeping good crystallinity of the double perovskite. Precursor phases and the final purity of the Sr2FeMoO6 powder can be controlled via hydrothermal microwave heating on the first stages of the Sol-Gel method.

Thermal quench in ITER locked mode disruptions

Simulations and theory are presented of an ITER locked mode thermal quench (TQ). In present experiments, locked mode disruptions have a long precursor phase, followed by a rapid termination and thermal quench, which can be identified with a resistive wall tearing mode (RWTM). In ITER, the RWTM will be slowed by the highly conductive vacuum vessel. The rapid termination might be absent, and the plasma could remain in the precursor phase. If the edge temperature is in the collisional regime, the TQ would proceed on a long timescale, limited by the RWTM to almost 100 ms. This is an important self-mitigating effect.

Evolution of 3D interconnected composites of high-entropy TiVNbMoTa alloys and Mg during liquid metal dealloying

The high-entropy alloy (HEA) design strategy is effective for ultra-coarsening-resistant 3D interconnected materials developed by liquid metal dealloying (LMD). However, the fundamental understanding of the dealloying mechanism and structural evolution of multi-principal elements 3D structured materials is still missing. In this study, the microstructural evolutions of 3D interconnected HEAs in Mg matrix were investigated using two types of multiphase precursors, namely, arc-melted and homogenized ones. The precursors' microstructure greatly influences dealloying kinetics and dealloying mechanisms what, in its turn, determines the final morphology of the 3D interconnected HEAs in Mg matrix. First, the prior fcc phase was dealloyed faster than any other precursor phases at dealloying temperatures from 600 to 900 °C. Second, the dealloying kinetics was faster along precursor grain boundaries (GB) as compared with grain interior. This led to the formation of a unique layered composite structure due to the inhomogeneous dealloying along the fine lamellars’ GB of the homogenized precursor. Moreover, governing orientation relationship between precursor and dealloying product depends on the LMD conditions, and it significantly affects the 3D interconnected grain structure. The fundamental understanding of the dealloying mechanisms will pave the way for customized morphology design of the 3D interconnected HEAs in metallic matrix with improved thermal stability and physical properties.

A Transient Coronal Sigmoid in Active Region NOAA 11909: Build-up Phase, M-class Eruptive Flare, and Associated Fast Coronal Mass Ejection

In this article, we investigate the formation and disruption of a coronal sigmoid from the active region (AR) NOAA 11909 on 07 December 2013, by analyzing multi-wavelength and multi-instrument observations. Our analysis suggests that the formation of the sigmoid initiated ≈ 1 hour before its eruption through a coupling between two twisted coronal loop systems. This sigmoid can be well regarded as of ‘transient’ class due to its short lifetime as the eruptive activities started just after ≈ 20 min of its formation. A comparison between coronal and photospheric images suggests that the coronal sigmoid was formed over a simple \(\beta \)-type AR which also possessed dispersed magnetic field structure in the photosphere. The line-of-sight photospheric magnetograms also reveal small-scale flux cancellation events near the polarity inversion line, and overall flux cancellation during the extended pre-eruption phase which suggest the role of tether-cutting reconnection toward the build-up of the flux rope. The disruption of the sigmoid proceeded with a two-ribbon eruptive M1.2 flare (SOL2013-12-07T07:29). In radio frequencies, we observe type III and type II bursts in meter wavelengths during the impulsive phase of the flare. The successful eruption of the flux rope leads to a fast coronal mass ejection (with a linear speed of ≈ 1085 km s−1) in SOHO/LASCO field-of-view. During the evolution of the flare, we clearly observe typical “sigmoid-to-arcade” transformation. Prior to the onset of the impulsive phase of the flare, flux rope undergoes a slow rise (≈ 15 km s−1) which subsequently transitions into a fast eruption (≈ 110 km s−1). The two-phase evolution of the flux rope shows temporal associations with the soft X-ray precursor and impulsive phase emissions of the M-class flare, respectively, thus pointing toward a feedback relationship between magnetic reconnection and early CME dynamics.

Magnesium partitioning into vaterite and its potential role as a precursor phase in foraminiferal Mg/Ca thermometer

The foraminifera shell Mg/Ca thermometer has been extensively used in reconstructing temperature evolution of the past oceans. An important, yet poorly understood observation is the 1-2 orders of magnitude lower Mg/Ca in foraminifera calcite shells than expected from inorganically precipitated calcite. Transient unstable carbonate was long hypothesized as a precursor of foraminiferal calcification, but its potential role in explaining apparent ‘vital effects’ of trace element partitioning is not well understood. In particular, a recent study has identified vaterite as a likely precursor phase during biomineralization of calcite foraminifera shells (Jacob et al., 2017). Here, we explore the possibility of vaterite as a precursor phase in affecting Mg incorporation into foraminifera calcite shells by experimentally calibrating the temperature dependent Mg partition coefficients between carbonate solution and vaterite under different solution Mg concentrations. The experimentally determined sensitivity of Mg incorporation into vaterite as a function of temperature (T in °C) is expressed as: ln⁡(λvateriteMg)=0.022±0.002⋅T−3.65±0.03. It is demonstrated that Mg partitioning is mainly controlled by the strain energy originated from cation substitution in the discontinuous lattices of vaterite particles, without distinct kinetic-controlled effects. We have developed a two-step partition model applying the above experimental results, with the assumption that vaterite is directly precipitated from a seawater-like fluid and later converts to calcite through dissolution-reprecipitation mediated by a second fluid in a localized environment. Within the constrained range of model parameters during phase conversion, the two-step partition model could directly reproduce foraminiferal calcite Mg/Ca temperature dependencies in both magnitude and sensitivity. Our model provides a theoretical framework that could be broadly applied to understand the impact of precursor phase on trace metal partition in biominerals. Overall, our study implies that the energy-consuming biological pumping of Mg outside foraminifera calcifying fluid, as widely believed, might not be a precondition for foraminifera shell mineralization.

Effect of phase type in the alumina precursor on the flash calcination synthesis

Economical alumina precursors, derived from bauxite or nepheline ores, were calcined through a very short time process. Results showed that phases of the precursor are a key parameter on the flash calcination process. The number of structural water molecules is the dominant phenomenon. A porous and fine structure of activated alumina was developed as the hydroxyl groups are explosively driven off and establish a hydrothermal condition. The presence of gibbsite phase with larger particle size and most structural water molecules has better product properties in comparison of other alumina precursors phase with small particle size because water vapor pressure achieves a critical value for splitting particles and developing nucleation desirable phases. The changes rate of properties reaches to its maximum value for gibbsite phase at lower calcination temperature. FESEM images showed the precursor phase forms different morphologies of products like, nanodimensional, a coral-like co-continuous or loose particles surrounded with macropores.

Citrate Stabilizes Hydroxylapatite Precursors: Implications for Bone Mineralization.

Mineralization of hydroxylapatite (HAp), the main inorganic phase in bone, follows nonclassical crystallization routes involving metastable precursors and is strongly influenced by organic macromolecules. However, the effect of small organic molecules such as citrate on the formation of HAp is not well constrained. Using potentiometric titration experiments and titration calorimetry, in combination with a multianalytical approach, we show that citrate stabilizes prenucleation species as well as a liquid-like calcium phosphate precursor formed before any solid phase nucleates in the system. The stabilization of a liquid-like precursor phase could facilitate infiltration into the cavities of the collagen fibrils during bone mineralization, explaining the enhancement of collagen-mediated mineralization by citrate reported in previous studies. Hence, citrate can influence bone mineralization way before any solid phase (amorphous or crystalline) is formed. We also show that HAp formation after amorphous calcium phosphate (ACP) in the absence and presence of citrate results in nanoplates of about 5–12 nm thick, elongated along the c axis. Such nanoplates are made up of HAp nanocrystallites with a preferred c axis orientation and with interspersed ACP. The nanoplatelet morphology, size, and preferred crystallographic orientation, remarkably similar to those of bone HAp nanocrystals, appear to be an intrinsic feature of HAp formed from an amorphous precursor. Our results challenge current models for HAp mineralization in bone and the role of citrate, offering new clues to help answer the long-standing question as to why natural evolution favored HAp as the mineral phase in bone.

Environment-friendly antisolvent tert-amyl alcohol modified hybrid perovskite photodetector with high responsivity

The preparation of high-quality perovskite films with optimal morphologies is important for achieving high-performance perovskite photodetectors (PPDs). An effective strategy to optimize the morphologies is to add antisolvents during the spin-coating steps. In this work, a novel environment-friendly antisolvent tert-amyl alcohol (TAA) is employed first to improve the quality of perovskite films, which can effectively regulate the formation of an intermediate phase staged in between a liquid precursor phase and a solid perovskite phase due to its moderate polarity and further promote the homogeneous nucleation and crystal growth, thus leading to the formation of high-quality perovskite films and enhanced photodetector performance. As a result, the responsivity of the PPD reaches 1.56 A/W under the illumination of 532 nm laser with the power density of 6.37 μW / cm 2 at a bias voltage of − 2 V , which is good responsivity for PPDs with the vertical structure and only CH 3 NH 3 PbI 3 perovskite as the photosensitive material. The corresponding detectivity reaches 1.47 × 10 12 Jones, while the linear dynamic range reaches 110 dB. These results demonstrate that our developed green antisolvent TAA has remarkable advantages for the fabrication of high-performance PPDs and can provide a reference for similar research work.

Structure and formation of amorphous calcium phosphate and its role as surface layer of nanocrystalline apatite: Implications for bone mineralization

We provide a critical review of the chemical composition and structure of synthetic and biogenic (bone/dentin mineral) nanocrystalline hydroxy-carbonate apatite (HCA). Such particles exhibit a “core–shell” organization, where an ordered HCA core is coated by a surface layer, whose nature is best captured by amorphous calcium phosphate (ACP), which is known to be a precursor phase of synthetic HCA, but whose role of bone/dentin mineralization has remained a most controversial subject. After reviewing the structure of each HCA and ACP component, as well as the most recent findings on their in vitro formation mechanisms, we examine the core–shell HCA organization further, with a focus on the disordered surface (“shell”) domain. In most of recent literature, the surface portion is often referred to as the “hydrated surface layer”, but without identifying its shared chemical and structural features of (synthetic) ACP. Unfortunately, that missing surface-layer/ACP equivalence obscures that the surface layer at the synthetic/biogenic nanocrystallites may simply constitute a remnant of the ACP phase from which the ordered HCA “core” nucleated. Although many topics reviewed herein have been investigated for more than six decades, several remain unsettled and heavily debated. Notably, decades-old articles offer suggestions that have passed unnoticed by the younger generations of researchers; we contrast and discuss both the latest and early contributions of this field, as well as highlighting several unsettled topics that should be revisited to improve our understanding of the ACP and HCA structures and in vitro/in vivo formation mechanisms.

Implication of polymeric template agent on the formation process of hybrid halide perovskite films

The use of polymeric additives supporting the growth of hybrid halide perovskites has proven to be a successful approach aiming at high quality active layers targeting optoelectronic exploitation. A detailed description of the complex process involving the self-assembly of the precursors into the perovskite crystallites in presence of the polymer is, however, still missing. Here we take starch:CH3NH3PbI3 (MAPbI3) as example of highly performing composite, both in solar cells and light emitting diodes, and study the film formation process through differential scanning calorimetry and in situ time-resolved grazing incidence wide-angle x-ray scattering, performed during spin coating. These measurements reveal that starch beneficially influences the nucleation and growth of the perovskite precursor phase, leading to improved structural properties of the resulting film which turns into higher stability towards environmental conditions.

High efficient co-doping in plasma electrolytic oxidation to obtain long-term self-lubrication on Ti6Al4V

Titanium alloys are important aerospace metals but suffer the poor mechanical property in high-loading area. Plasma electrolytic oxidation can improve their hardness and reduce friction but the precursor competition of functional phases in PEO electrolyte is inevitable. This work provides a new strategy to avoid ions competition and precipitation by choosing anionic salt (K2ZrF6) and cationic salt (Ce(Ac)3) as the precursors of the hard phase (ZrO2) and lubrication phase (monoclinic CePO4), respectively. As a result, the ions competition is avoided to achieve simultaneous high-content doping of functional phases. The optimized coating shows a maximum hardness of 626 HV, small friction coefficient of 0.12 and a lower wear rate of only 3.1 × 10−5 ± 0.15 mm3 N−1 m−1, indicating excellent long-term self-lubrication property and wear resistance.