A specialized metabolic pathway partitions citrate in hydroxyapatite to impact mineralization of bones and teeth.

Citrate is a critical metabolic substrate and key regulator of energy metabolism in mammalian cells. It has been known for decades that the skeleton contains most (>85%) of the body's citrate, but the question of why and how this metabolite should be partitioned in bone has received singularly little attention. Here, we show that osteoblasts use a specialized metabolic pathway to regulate uptake, endogenous production, and the deposition of citrate into bone. Osteoblasts express high levels of the membranous Na+-dependent citrate transporter solute carrier family 13 member 5 (Slc13a5) gene. Inhibition or genetic disruption of Slc13a5 reduced osteogenic citrate uptake and disrupted mineral nodule formation. Bones from mice lacking Slc13a5 globally, or selectively in osteoblasts, showed equivalent reductions in cortical thickness, with similarly compromised mechanical strength. Surprisingly, citrate content in mineral from Slc13a5-/- osteoblasts was increased fourfold relative to controls, suggesting the engagement of compensatory mechanisms to augment endogenous citrate production. Indeed, through the coordinated functioning of the apical membrane citrate transporter SLC13A5 and a mitochondrial zinc transporter protein (ZIP1; encoded by Slc39a1), a mediator of citrate efflux from the tricarboxylic acid cycle, SLC13A5 mediates citrate entry from blood and its activity exerts homeostatic control of cytoplasmic citrate. Intriguingly, Slc13a5-deficient mice also exhibited defective tooth enamel and dentin formation, a clinical feature, which we show is recapitulated in primary teeth from children with SLC13A5 mutations. Together, our results reveal the components of an osteoblast metabolic pathway, which affects bone strength by regulating citrate deposition into mineral hydroxyapatite.

Polymer Chains Fold Prior to Crystallization.

There are long-standing debates in crystallization mechanism of polymer chains at the molecular levels: Which comes first, chain folding or lamellae formation during crystallization? In this study, we report the local chain trajectory of 13C-labeled semicrystalline polymer in an extreme case of rapidly quenched glassy state as well as thermodynamically stable crystals formed via different pathways from glass and melt. Magnetically dipole interactions do not require a long-range order of molecular objects and thus enable us to trace the local chain trajectory of polymer chains even in a glassy state. To accurately characterize the local chain trajectory of polymer glass, the natural abundance effect on 13C-13C double-quantum (DQ) nuclear magnetic resonance (NMR) signal is re-examined using extended chain conformation. As results, it is found that glassy chains adopt the same adjacent re-entry structure (adjacent re-entry number, n = 1) with the melt- and cold-grown crystals. From these results, it is concluded that (i) folding occurs prior to crystallization and (ii) melt and cold crystallization do not induce additional folding but proceed with rearrangements of polymer chains in the existing templates.

The role of foreign capital and economic freedom in sustainable food production: Evidence from DLD countries.

In many developing countries, the deficiency in public and private investment has resulted in lower growth rates and stagnation in productivity. The need for a new paradigm of foreign investment and aid in agricultural production is becoming exigent in developing countries. Given the decline in per capita arable land, the rise in production costs, and the increase in population and urbanization, major changes in agriculture have been proposed to boost agricultural production. This present study endeavours to contribute to the existing literature by proving whether foreign capital and economic freedom could catapult food production into the much-anticipated growth. In that regard, we performed GLS with correlated disturbances, system GMM dynamic panel data estimators and D-H causality test. The study found that foreign capital as a whole plays a positive role in food production in developing and least developed countries, but FDI is insignificant in least-developed countries. Moreover, economic freedom plays a positive role in food production in least-developed countries but negative in developing countries. Policymakers and governments should create an enabling environment for sustainable food production.

Perfect and Defective 13C-Furan-Derived Nanothreads from Modest-Pressure Synthesis Analyzed by 13C NMR.

The molecular structure of nanothreads produced by the slow compression of 13C4-furan was studied by advanced solid-state NMR. Spectral editing showed that >95% of carbon atoms were bonded to one hydrogen (C-H) and that there were 2-4% CH2, 0.6% C═O, and <0.3% CH3 groups. Alkenes accounted for 18% of the CH moieties, while trapped, unreacted furan made up 7%. Two-dimensional (2D) 13C-13C and 1H-13C NMR identified 12% of all carbon in asymmetric O-CH═CH-CH-CH- and 24% in symmetric O-CH-CH═CH-CH- rings. While the former represented defects or chain ends, some of the latter appeared to form repeating thread segments. Around 10% of carbon atoms were found in highly ordered, fully saturated nanothread segments. Unusually slow 13C spin-exchange with sites outside the perfect thread segments documented a length of at least 14 bonds; the small width of the perfect-thread signals also implied a fairly long, regular structure. Carbons in the perfect threads underwent relatively slow spin-lattice relaxation, indicating slow spin exchange with other threads and smaller amplitude motions. Through partial inversion recovery, the signals of the perfect threads were observed and analyzed selectively. Previously considered syn-threads with four different C-H bond orientations were ruled out by centerband-only detection of exchange NMR, which was, on the contrary, consistent with anti-threads. The observed 13C chemical shifts were matched well by quantum-chemical calculations for anti-threads but not for more complex structures like syn/anti-threads. These observations represent the first direct determination of the atomic-level structure of fully saturated nanothreads.

Immobilized 13C-labeled polyether chain ends confined to the crystallite surface detected by advanced NMR.

A comprehensive 13C nuclear magnetic resonance (NMR) approach for characterizing the location of chain ends of polyethers and polyesters, at the crystallite surface or in the amorphous layers, is presented. The OH chain ends of polyoxymethylene are labeled with 13COO-acetyl groups and their dynamics probed by 13C NMR with chemical shift anisotropy (CSA) recoupling. At least three-quarters of the chain ends are not mobile dangling cilia but are immobilized, exhibiting a powder pattern characteristic of the crystalline environment and fast CSA dephasing. The location and clustering of the immobilized chain ends are analyzed by spin diffusion. Fast 1H spin diffusion from the amorphous regions shows confinement of chain ends to the crystallite surface, corroborated by fast 13C spin exchange between chain ends. These observations confirm the principle of avoidance of density anomalies, which requires that chains terminate at the crystallite surface to stay out of the crowded interfacial layer.

Structure of the Polymer Backbones in polyMOF Materials.

The molecular connectivity of polymer-metal-organic framework (polyMOF) hybrid materials was investigated using density functional theory calculations and solid-state NMR spectroscopy. The architectural constraints that dictate the formation of polyMOFs were assessed by examining poly(1,4-benzenedicarboxylic acid) (pbdc) polymers in two archetypical MOF lattices (UiO-66 and IRMOF-1). Modeling of the polyMOFs showed that in the IRMOF-1-type lattice, six, seven, and eight methylene (-CH2-) groups between 1,4-benzenedicarboxylate (terephthalate, bdc2-) units can be accommodated without significant distortions, while in the UiO-66-type lattice, an optimal spacing of seven methylene groups between bdc2- units is needed to minimize strain. Solid-state NMR supports these predictions and reveals pronounced spectral differences for the same polymer in the two polyMOF lattices. With seven methylene groups, polyUiO-66-7a shows 7 ± 3% of uncoordinated terephthalate linkers, while these are undetectable (<4%) in the corresponding polyIRMOF-1-7a. In addition, NMR-detected backbone mobility is significantly higher in the polyIRMOF-1-7a than in the corresponding polyUiO-66-7a, again indicative of taut chains in the latter.

Rapid Depolymerization of Decrystallized Cellulose to Soluble Products via Ethanolysis under Mild Conditions.

Efficient cellulose depolymerization is a major bottleneck for economical production of second-generation biofuels. In this work, crystalline cellulose was subjected to sequential ball milling and ethanolysis as a mild and selective depolymerization approach. Ball milling and ethanolysis resulted in 38±1 % cellulose conversion, with 24 % ethyl-glucopyranoside as the main identified and quantified product and negligible side reaction of the ethanol solvent to form diethyl ether. In comparison, ethanolysis of the original cellulose resulted in only 3±1 % conversion. Additional soluble products from cellulose ethanolysis included carbohydrate isomers and oligomers, differing from the products obtained from hydrolysis. X-ray diffraction and nuclear magnetic resonance spectroscopy revealed increased crystallinity post-reaction, retarding further depolymerization. Hot liquid water extracted soluble oligomers from the ethanolyzed cellulose, suggesting formation of a nanoscale barrier of crystalline cellulose that traps soluble products during ethanolysis. Use of cellulose-swelling co-solvents and repeated mechanical decrystallization both proved effective at increasing cellulose conversion and soluble product yields. Repeated ball milling and ethanolysis resulted in 62±1 % cellulose conversion. Ethanolysis of decrystallized cellulose has potential for rapid (<2 h) de-polymerization at mild conditions.

Novel Lewis Base Cyclam Self-Passivation of Perovskites without an Anti-Solvent Process for Efficient Light-Emitting Diodes.

Metal halide perovskites have been focused as a candidate applied as a promising luminescent material for next-generation high-quality lighting and high-definition display. However, as perovskite films formed, high density of defects would be produced in solution processing inevitably, leading to low exciton recombination efficiency in light-emitting diodes (LEDs). Herein, a facile and novel self-passivation strategy to inhibit defect formation in perovskite films for constructing high-performance LEDs is developed. For the first time, we introduce 1,4,8,11-tetraazacyclotetradecane (cyclam) in perovskite precursor solution, and it spontaneously passivates defect states of CsPbBr3-based perovskites by coaction between amine and uncoordinated lead ions during spin-coating without an anti-solvent process. Furthermore, as a delocalized system, cyclam also possesses chemical properties that facilitate exciton transportation. The proposed passivation strategy boosts the external quantum efficiency from 1.25% (control device) to 16.24% (cyclam-passivated device). Furthermore, defect passivation is also conductive to reduce LED degradation paths and improve device stability as the extrapolated lifetime (T50) of LEDs at an initial brightness of 100 cd/m2 is increased from 0.9 to 127 h. These findings indicate that the introduction of cyclam is highly effective to enhance the performance of LEDs, and such a strategy in effectively reducing the defects could be also applied in other perovskite-based devices, such as lasers, solar cells, and photodetectors.

Multinuclear solid-state NMR of complex nitrogen-rich polymeric microcapsules: Weight fractions, spectral editing, component mixing, and persistent radicals.

The molecular structure of a crosslinked nitrogen-rich resin made from melamine, urea, and aldehydes, and of microcapsules made from the reactive resin with multiple polymeric components in aqueous dispersion, has been analyzed by 13C, 13C{1H}, 1H-13C, 1H, 13C{14N}, and 15N solid-state NMR without isotopic enrichment. Quantitative 13C NMR spectra of the microcapsules and three precursor materials enable determination of the fractions of different components. Spectral editing of non-protonated carbons by recoupled dipolar dephasing, of CH by dipolar DEPT, and of C-N by 13C{14N} SPIDER resolves peak overlap and helps with peak assignment. It reveals that the N- and O-rich resin "imitates" the spectrum of polysaccharides such as chitin, cellulose, or Ambergum to an astonishing degree. 15N NMR can distinguish melamine from urea and guanazole, NC=O from COO, and primary from secondary amines. Such a comprehensive and quantitative analysis enables prediction of the elemental composition of the resin, to be compared with combustion analysis for validation. It also provides a reliable reference for iterative simulations of 13C NMR spectra from structural models. The conversion from quantitative NMR peak areas of structural components to the weight fractions of interest in industrial practice is derived and demonstrated. Upon microcapsule formation, 15N and 13C NMR consistently show loss of urea and aldehyde and an increase in primary amines while melamine is retained. NMR also made unexpected findings, such as imbedded crystallites in one of the resins, as well as persistent radicals in the microcapsules. The crystallites produce distinct sharp lines and are distinguished from liquid-like components by their strong dipolar couplings, resulting in fast dipolar dephasing. Fast 1H spin-lattice relaxation on the 35-ms time scale and characteristically non-exponential 13C spin-lattice relaxation indicate persistent radicals, confirmed by EPR. Through 1H spin diffusion, the mixing of components on the 5-nm scale was documented.

Phase transition of spiropyrans: impact of isomerization dynamics at high temperatures.

Isomerization behaviors of spiropyran derivatives in neat condensed phase were studied to understand their unusual phase transitions including cold-crystallization after extreme supercooling down to -50 °C. Compounds with different functional groups were compared, and the equilibrium between isomers at high temperatures was found to determine phase transitions.

Synthesis of stable and phase-adjustable CsPbBr3@Cs4PbBr6 nanocrystals via novel anion-cation reactions.

All-inorganic cesium lead halide perovskites have emerged as promising semiconductor materials due to their preeminent performance in lighting, display, light detecting, and laser fields. However, the applications of lead halide perovskites are limited by the dissatisfactory stability owing to their fragile ionic crystal characteristics and highly dynamic surface-coordinated states. The in situ diphase structure passivation possessing the same chemical constituents (such as passivating CsPbBr3 with Cs4PbBr6) has been proven to be an effective way to improve the stabilities and simultaneously maintain the highly efficient luminescence properties. Herein, for the first time, we report a novel anion-cation reaction method to synthesize the lead halide perovskite NCs with diphase CsPbBr3@Cs4PbBr6 structure. Moreover, we have found that the phase transformation between CsPbBr3 and Cs4PbBr6 is temperature dependent. Thus, we could control the relative composition of the diphase CsPbBr3@Cs4PbBr6 composite by adjusting the temperature. The optimized CsPbBr3@Cs4PbBr6 composite NCs achieve highly light emissive performance and stabilities against atmosphere, moisture and heating. Furthermore, we could obtain 135% of the NTSC color gamut through anion exchange. These highly emissive composite NCs with improved stabilities exhibit great potential in future optoelectronic fields.

Stoichiometry and Packing Structure of Poly(lactic acid) Stereocomplex as Revealed by Solid-State NMR and 13C Isotope Labeling.

Poly(l-lactic acid) (L)/poly(d-lactic acid) (D) blends form a stereocomplex (SC) at a mixing ratio of 7/3-3/7. The stoichiometry and packing structure of L/D in the SC are controversial topics because the SC is semicrystalline and because the enantiomeric pair has the same chemical structure. In this study, both the stoichiometry and packing structure of 33% 13C CH3-labeled (l) L/nonlabeled D blends at mixing ratios of 7/3-3/7 were investigated by using solid-state (SS) NMR. The 13C CO signals in natural abundance provided the fractions of the SC (ΦSC), α, and amorphous regions of l-L/D blends. Moreover, the 33% 13CH3-labeled signals could determine the fraction of only l-L in the SC (ΦL) and amorphous region. These two data sets allowed us to determine the stoichiometry of l-L/D in the SC (ΦL-SC/ΦD-SC) to be 1/1. 13C-13C double-quantum (DQ) buildup curves of l-L in the SC followed one universal curve even at different mixing ratios. Comparison of the experimental and simulated DQ curves led to the conclusion that all SC crystals adopt a regular packing structure at varied mixing ratios.

Chain Trajectory, Chain Packing, and Molecular Dynamics of Semicrystalline Polymers as Studied by Solid-State NMR.

Chain-level structure of semicrystalline polymers in melt- and solution-grown crystals has been debated over the past half century. Recently, 13C⁻13C double quantum (DQ) Nuclear Magnetic Resonance (NMR) spectroscopy has been successfully applied to investigate chain-folding (CF) structure and packing structure of 13C enriched polymers after solution and melt crystallization. We review recent NMR studies for (i) packing structure, (ii) chain trajectory, (iii) conformation of the folded chains, (iv) nucleation mechanisms, (v) deformation mechanism, and (vi) molecular dynamics of semicrystalline polymers.

Chain Trajectory of Semicrystalline Polymers As Revealed by Solid-State NMR Spectroscopy.

Over the last half century, a chain-folding structure of semicrystalline polymers has been debated in polymer science. Recently, 13C-13C double quantum (DQ) NMR spectroscopy combined with 13C selective isotope labeling has been developed to investigate re-entrance sites of the folded chains, mean values of adjacent re-entry number ⟨n⟩ and fraction ⟨F⟩ of semicrystalline polymers. This viewpoint highlights the versatile approaches of using solid-state (ss) NMR and isotope labeling for revealing (i) chain trajectory in melt- and solution-grown crystals, (ii) conformation of the folded chains in single crystals, (iii) self-folding in the early stage of crystallization, and (iv) unfolding of the folded chains under stretching.

Unfolding of Isotactic Polypropylene under Uniaxial Stretching.

Despite numerous investigations on polymer processing, understanding the deformation mechanisms of semicrystalline polymer under uniaxial stretching is still challenging. In this work, 13C-13C Double Quantum (DQ) NMR was applied to trace the structural evolution of 13C-labeled isotactic polypropylene (iPP) chains inside the crystallites stretched to an engineering strain (e) of 21 at 100 °C. DQ NMR based on spatial proximity of 13C labeled nuclei proved conformational changes from the folded chains to the locally extended chains induced by stretching. By combining experimental findings with literature results on molecular dynamics, it was concluded that transportation of the crystalline chains plays a critical role to achieve large deformability of iPP.

Three-Dimensional Conformation of Folded Polymers in Single Crystals.

The chain-folding mechanism and structure of semicrystalline polymers have long been controversial. Solid-state NMR was applied to determine the chain trajectory of (13)C CH3-labeled isotactic poly(1-butene) (iPB1) in form III chiral single crystals blended with nonlabeled iPB1 crystallized in dilute solutions under low supercooling. An advanced (13)C-(13)C double-quantum NMR technique probing the spatial proximity pattern of labeled (13)C nuclei revealed that the chains adopt a three-dimensional (3D) conformation in single crystals. The determined results indicate a two-step crystallization process of (i) cluster formation via self-folding in the precrystallization stage and (ii) deposition of the nanoclusters as a building block at the growth front in single crystals.

Determination of Local Packing Structure of Mesomorphic Form of Isotactic Polypropylene by Solid-State NMR.

Understanding the local packing structures of a disordered mesomorphic phase is a challenging issue in polymer characterization. In this work, 13C-13C through-space interactions, as well as a molecular dynamics analysis based on the reorientation of chemical shift anisotropy (CSA), were proposed for the evaluation of the local packing structure of the mesomorphic form of isotactic polypropylene (iPP). 13C-13C double quantum (DQ) buildup curves of 13C 15% CH3 selectively labeled iPP and spin-dynamics simulations demonstrated that the local packing structures in the mesomorphic form were very similar to the packing in the ß phase. Moreover, centerband only detection of exchange (CODEX) NMR proved that the correlation time ⟨τc⟩ of the overall stem dynamics in the mesomorphic form followed the same Arrhenius line observed for the ß phase, but it deviated from that for the α phase. Based on both structural and dynamic results, it was concluded that the local packing structure in the mesomorphic form was exceedingly close or the same as that of the ß phase.

Folding of Polymer Chains in the Early Stage of Crystallization.

Understanding the structure formation of an ordered domain in the early stage of crystallization is one of the long-standing issues in polymer science. In this study, we investigate the chain trajectory of isotactic polypropylene (iPP) formed via rapid and deep quenching, using solid-state NMR spectroscopy. Comparisons of experimental and simulated 13C-13C double quantum (DQ) buildup curves demonstrated that individual iPP chains adopt adjacent re-entry sequences with an average folding number ⟨n⟩ = 3-4 in the mesomorphic form, assuming an adjacent re-entry fraction ⟨F⟩ of 100%. Therefore, long flexible polymer chains naturally fold in the early stage of crystallization, and folding-initiated nucleation results in formation of mesomorphic nanodomains.