Non-classical Pathway Research Articles

Near-Death Cells Cause Chemotherapy-Induced Metastasis via ATF4-Mediated NF-κB Signaling Activation.

Cytotoxic chemotherapy is a primary treatment modality for many patients with advanced cancer. Increasing preclinical and clinical observations indicate that chemotherapy can exacerbate tumor metastasis. However, the underlying mechanism remains unclear. Here, it is attempted to identify the mechanisms underlying chemotherapy-induced cancer recurrence and metastasis. It is revealed that a small subpopulation of "near-death cells" (NDCs) with compromised plasma membranes can reverse the death process to enhance survival and repopulation after exposure to lethal doses of cytotoxins. Moreover, these NDCs acquire enhanced tumorigenic and metastatic capabilities, but maintain chemosensitivity in multiple models. Mechanistically, cytotoxin exposure induces activating transcription factor 4 (ATF4)-dependent nonclassical NF-κB signaling activation; ultimately, this results in nuclear translocation of p52 and RelB in NDCs. Deletion of ATF4 in parental cancer cells significantly reduces colony formation and metastasis of NDCs, whereas overexpression of ATF4 activates the nonclassical NF-κB signaling pathway to promote chemotherapy-induced metastasis of NDCs. Overall, these results provide novel mechanistic insights into the chemotherapy-induced metastasis and indicate the pivotal role of NDCs in mediating tumor relapse after cytotoxic therapy. This study also suggests that targeting ATF4 may be an effective approach in improving the efficacy of chemotherapy.

Uncovering the Early Stages of Magnesium Silicate Hydrate Formation: A Nonclassical Multistep Pathway

Understanding the fundamental physicochemical processes that occur during the hydration of cementitious materials is essential for developing alternative binders that enable the partial substitution of Portland cement (PC), lowering the carbon footprint associated with the cement industry. Magnesium-silicate-hydrate (M-S-H) stands as a potential alternative binder; however, its inferior mechanical properties attributed to its nanostructure, and the high-water demand for curing, hinder the application of MgO-based cement as PC surrogate. A potential strategy to tackle these major drawbacks is based on controlling M-S-H formation from the early stages, building the properties and nanostructure of this binding phase from its basic building units. The present work provides insights into M-S-H nucleation and early growth gathered by combining titration experiments with electrospray ionization mass spectrometry, analytical ultracentrifugation, and transmission electron microscopy. We evidenced a nonclassical multistep pathway where a highly complex mixture of defined hydrated magnesium (sodium)-silicate oligomeric species exists in solution prior nucleation. Our results suggest that these entities aggregate, yielding an ill-defined M-S-H precursor phase (depleted in Mg compared to the final product) which later transforms into a denser M-S-H interconnected network (Mg:Si ratio ca. 1) with a more defined sheet-like structure that still retains its poorly crystalline character. The identification of oligomeric silicates species prior nucleation is of great importance for developing means to regulate M-S-H (and potentially other hydrous silicates) formation by using a bottom-up approach. This work reveals that, during the hydration process of cementitious materials, the stages prior to the formation of hydrated solids cannot be disregarded, as they could open new avenues for engineering the properties of the final materials.

Nucleation experiments on a titanium-carbon system imply nonclassical formation of presolar grains.

Just as the shapes of snowflakes provide us with information on the temperature and humidity of the upper atmosphere, the characteristics of presolar grains in meteorites place limits on their formation environment in a stellar outflow. However, even in the case of well-characterized presolar grains consisting of a titanium carbide core and a graphitic carbon mantle, it is not possible to delimit their formation environment. Here, we have demonstrated the formation of core-mantle grains in gravitational and microgravity environments and have found that core-mantle grains are formed by a nonclassical nucleation pathway involving the three steps: (i) primary nucleation of carbon at a substantially high supersaturation, (ii) heterogeneous condensation of titanium carbide on the carbon, and (iii) fusion of nuclei. We argue that the characteristics of not only core-mantle grains but also other presolar and solar grains might be accurately explained by considering a nonclassical nucleation pathway.

In Situ Imaging of Faujasite Surface Growth Reveals Unique Pathways of Zeolite Crystallization.

Zeolite crystallization occurs by complex processes involving a variety of possible mechanisms. The sol gel media used to prepare zeolites leads to heterogeneous mixtures of solution and solid states with diverse solute species. At later stages of zeolite synthesis when growth occurs predominantly from solution, classical two-dimensional nucleation and spreading of layers on crystal surfaces via the addition of soluble species is the dominant pathway. At earlier stages, these processes occur in parallel with nonclassical pathways involving crystallization by particle attachment (CPA). The relative roles of solution- and solid-state species in zeolite crystallization have been a subject of debate. Here, we investigate the growth mechanism of a commercially relevant zeolite, faujasite (FAU). In situ atomic force microscopy (AFM) measurements reveal that supernatant solutions extracted from a conventional FAU synthesis at various times do not result in growth, indicating that FAU growth predominantly occurs from the solid state through a disorder-to-order transition of amorphous precursors. Elemental analysis shows that supernatant solutions are significantly more siliceous than both the original growth mixture and the FAU zeolite product; however, in situ AFM studies using a dilute clear solution with a lower Si/Al ratio revealed three-dimensional growth of surfaces that is distinct from layer-by-layer and CPA pathways. This unique mechanism of growth differs from those observed in studies of other zeolites. Given that relatively few zeolite frameworks have been the subject of mechanistic investigation by in situ techniques, these observations of FAU crystallization raise the question whether its growth pathway is characteristic of other zeolite structures.

Accelerating High-Performance Classification of Bacterial Proteins Secreted Via Non-Classical Pathways: No Needing for Deepness

Accelerating High-Performance Classification of Bacterial Proteins Secreted Via Non-Classical Pathways: No Needing for Deepness

Metal-rich cascade nanosystem for dual-pathway ferroptosis resistance regulation and photothermal effect for efficient tumor combination therapy.

Despite the therapeutic response of ferroptosis in various tumors, ferroptosis resistance has been found in numerous studies, significantly hindering the progress of ferroptosis anti-tumor therapy. Herein, we propose a metal-rich cascade nanosystem (Simvastatin-HMPB-Mn@GOx) combined with the dual-pathway regulation of ferroptosis resistance and photothermal therapy for efficient tumor combination therapy. The manganese-bonded hollow mesoporous Prussian blue (HMPB-Mn) serves as the photothermal agent and metal donor, and dissociates multivalent metal ions Mn2+, Fe3+ and Fe2+ to consume glutathione and amplify the Fenton reaction. Glucose oxidase (GOx) absorbed serves as the converter to provide hydrogen peroxide (H2O2) for the cascade Fenton reaction, causing a high burst of hydroxyl radicals (˙OH) and lipid peroxidation. Simvastatin innovatively acts as a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) inhibitor to decrease the expression of coenzyme Q10 (CoQ10) and glutathione peroxidase 4 (GPX4), eventually defeating ferroptosis resistance. The nanosystem acted in both classical and non-classical ferroptosis pathways and showed significant ferroptosis- and hyperthermia-induced anti-tumor efficacy both in vitro and in vivo. Thus, this study offers a promising way for ferroptosis and phototherapy to achieve complete tumor regression.

Conventional and non-conventional antigen presentation by mast cells.

Mast cells (MCs) are multifunctional immune cells that express a diverse repertoire of surface receptors and pre-stored bioactive mediators. They are traditionally recognized for their involvement in allergic and inflammatory responses, yet there is a growing body of literature highlighting their contributions to mounting adaptive immune responses. In particular, there is growing evidence that MCs can serve as antigen-presenting cells, owing to their often close proximity to T cells in both lymphoid organs and peripheral tissues. Recent studies have provided compelling support for this concept, by demonstrating the presence of antigen processing and presentation machinery in MCs and their ability to engage in classical and non-classical pathways of antigen presentation. However, there remain discrepancies and unresolved questions regarding the extent of the MC's capabilities with respect to antigen presentation. In this review, we discuss our current understanding of the antigen presentation by MCs and its influence on adaptive immunity.

Regulation of Cell Membrane Permeability Enhanced the Non-Classical Secretion of γ-Cyclodextrin Glycosyltransferase in Bacillus subtilis

γ-Cyclodextrin glycosyltransferase (γ-CGTase, EC 2.4.1.19) is an essential enzyme required in the production of γ-cyclodextrin, which shows huge prospects in the food, medicine, materials, and chemical industries. In this study, γ-CGTase from Bacillus sp. G-825-6 STB17 was successfully cloned and expressed in Bacillus subtilis WB600. The final extracellular activity of γ-CGTase can reach 45.34 U/mL with the deletion of the signal peptide, which was about 11.3 times of the initial level of γ-CGTase secreted by the general pathway. By monitoring the whole cultivation process, secretion was divided into two stages, which were dominated by cell membrane changes and apoptosis. The measurement of lactate dehydrogenase and the results of fluorescence microscopy demonstrated that the cell membrane permeability changed significantly in the middle stage of fermentation, proving that it played a crucial role in the non-classical secretion of γ-CGTase. Furthermore, the addition of Triton X-100, a non-ionic surfactant, remarkably enhanced the secretion level of γ-CGTase by 21.5%, which was caused by the increase in cell membrane permeability. This work is the first to obtain the extracellular expression of CGTase via the non-classical secretion pathway in B. subtilis and provides a new strategy to enhance extracellular expression by regulating the cell membranes.

Mycobacterium tuberculosis PE_PGRS19 Induces Pyroptosis through a Non-Classical Caspase-11/GSDMD Pathway in Macrophages.

The PE/PPE protein family commonly exists in pathogenic species, such as Mycobacterium tuberculosis, suggesting a role in virulence and its maintenance. However, the exact role of most PE/PPE proteins in host-pathogen interactions remains unknown. Here, we constructed a recombinant Mycobacterium smegmatis expressing M. tuberculosis PE_PGRS19 (Ms_PE_PGRS19) and found that PE_PGRS19 overexpression resulted in accelerated bacterial growth in vitro, increased bacterial survival in macrophages, and enhanced cell damage capacity. Ms_PE_PGRS19 also induced the expression of pro-inflammatory cytokines, such as IL-6, TNF-α, IL-1β, and IL-18. Furthermore, we demonstrated that Ms_PE_PGRS19 induced cell pyroptosis by cleaving caspase-11 via a non-classical pathway rather than caspase-1 activation and further inducing the cleavage of gasdermin D, which led to the release of IL-1β and IL-18. To the best of our current knowledge, this is the first report of a PE/PPE family protein activating cell pyroptosis via a non-classical pathway, which expands the knowledge on PE/PPE protein functions, and these pathogenic factors involved in bacterial survival and spread could be potential drug targets for anti-tuberculosis therapy.

Controlling quantum effects in enhanced strong-field ionisation with machine-learning techniques

We study non-classical pathways and quantum interference in enhanced ionisation of diatomic molecules in strong laser fields using machine learning techniques. Quantum interference provides a ‘bridge’, which facilitates intramolecular population transfer. Its frequency is higher than that of the field, intrinsic to the system and depends on several factors, for instance the state of the initial wavepacket or the internuclear separation. Using dimensionality reduction techniques, namely t-distributed stochastic neighbour embedding and principal component analysis, we investigate the effect of multiple parameters at once and find optimal conditions for enhanced ionisation in static fields, and controlled ionisation release for two-colour driving fields. This controlled ionisation manifests itself as a step-like behaviour in the time-dependent autocorrelation function. We explain the features encountered with phase-space arguments, and also establish a hierarchy of parameters for controlling ionisation via phase-space Wigner quasiprobability flows, such as specific coherent superpositions of states, electron localisation and internuclear-distance ranges.

Abstract 116: Regulation Of Nampt Secretion From Human Neutrophils By The Trpv2 Channel

Introduction: Nampt functions both as an intracellular enzyme critical for NAD + salvage and a novel extracellular damage-associated molecular pattern. In a mouse model of cardiac arrest, increased plasma Nampt correlates with inflammation, cardiovascular dysfunction and death. The mechanism that regulates Nampt secretion during cardiac arrest is not known. Hypothesis: We hypothesize that Nampt secretion is regulated by a non-selective cation channel TRPV2. Methods: Extracellular Nampt (eNampt) concentration was measured by ELISA. Neutrophils were isolated from human peripheral blood. Results: In non-stimulated human neutrophils incubated at 37 o C, eNampt was observed in cell supernatants at 10 min and plateaued after 30 min. eNampt is not released by the ER-Golgi classical pathway. Brefeldin A, an inhibitor of protein transport from ER to Golgi had no effect on eNampt release. Similarly, nocodazole, which disrupts microtubule assembly, had no effect on eNampt release either. eNampt release was markedly reduced at 4 o C, suggesting that the release is active. eNampt release was regulated by extracellular pH. The decline in pH from 7.4 to 6.5 suppressed the secretion of eNampt, while the increase of pH from 7.4 to 7.8 enhanced the amounts of eNampt release. We therefore reasoned that ion channels sensitive to pH and/or involved in intracellular pH homeostasis might play a role in Nampt secretion. 10 μM 5-(N,N-Hexamethylene) amiloride had no effect on eNampt release, which indicates that Na + /H + exchanger is not involved in eNampt release. In contrast, eNampt release was upregulated by the TRPV2 agonists 200 μM H 2 O 2 , 1 mM 2-aminoethoxydiphenyl borate and10 μM anandamide, and downregulated byTRPV2 inhibitors 0.5 mM EGTA, 5 mM NAM, 100 μM tranilast and 100 μM piperlongumine. Conclusion: Nampt is secreted from neutrophils via a non-classical pathway and its secretion is regulated by the pH sensitive TRPV2 channel.

Vacancy infilling during the crystallization of Fe-deficient hematite: An in situ synchrotron X-ray diffraction study of non-classical crystal growth

Abstract The crystallization of hematite from precursor ferrihydrite was studied using time-resolved, angle-dispersive synchrotron X-ray diffraction in aqueous solutions at pH 10 and 11 and at temperatures ranging from 80 to 170 °C. Rietveld analyses revealed a non-classical crystallization pathway involving vacancy infilling by Fe as defective hematite nanocrystals evolved. At 90 °C and pH 11, incipient hematite particles exhibited an Fe site occupancy as low as 0.68(2), and after 30 min, Fe occupancy plateaued at 0.84(1), achieving a metastable steady state with a composition corresponding to “hydrohematite.” During crystal growth, unit-cell volume increased with an increase in Fe occupancy. The increase in Fe occupancy in hydrohematite was accomplished by deprotonation, resulting in a shortening of the long Fe-O(H) bonds and decreased distortion of the octahedral sites. Once the occupancy stabilized, the unit-cell volume contracted following further nanoparticle growth. Our study documented various synthetic routes to the formation of “hydrohematite” with an Fe vacancy of 10–20 mol% in the final product. The structure refined for synthetic hydrohematite at 90 °C and pH 11 closely matched that of natural hydrohematite from Salisbury, Connecticut, with a refined Fe occupancy of 0.83(2). Dry heating this natural hydrohematite generated anhydrous, stoichiometric hematite, again by continuous infilling of vacancies. The transformation initiated at 150 °C and was complete at 700 °C, and it was accompanied by the formation of a minor amorphous phase that served as a reservoir for Fe during the inoculation of the defective crystalline phase.

Which Surface Is More Scaling Resistant? A Closer Look at Nucleation Theories for Heterogeneous Gypsum Nucleation in Aqueous Solutions.

Developing engineered surfaces with scaling resistance is an effective means to inhibit surface-mediated mineral scaling in various industries including desalination. However, contrasting results have been reported on the relationship between scaling potential and surface hydrophilicity. In this study, we combine a theoretical analysis with experimental investigation to clarify the effect of surface wetting property on heterogeneous gypsum (CaSO4·2H2O) formation on surfaces immersed in aqueous solutions. Theoretical prediction derived from classical nucleation theory (CNT) indicates that an increase of surface hydrophobicity reduces scaling potential, which contrasts our experimental results that more hydrophilic surfaces are less prone to gypsum scaling. We further consider the possibility of nonclassical pathway of gypsum nucleation, which proceeds by the aggregation of precursor clusters of CaSO4. Accordingly, we investigate the affinity of CaSO4 to substrate surfaces of varied wetting properties via calculating the total free energy of interaction, with the results perfectly predicting experimental observations of surface scaling propensity. This indicates that the interactions between precursor clusters of CaSO4 and substrate surfaces might play an important role in regulating heterogeneous gypsum formation. Our findings provide evidence that CNT might not be applicable to describing gypsum scaling in aqueous solutions. The fundamental insights we reveal on gypsum scaling mechanisms have the potential to guide rational design of scaling-resistant engineered surfaces.

Crystallization pathways, fabrics and the capture of climate proxies in speleothems: Examples from the tropics

The quality of climate proxy data from speleothem archives depends to varying degrees on crystallization processes, which result in diverse fabrics. Here, we document shifts in calcite growth mechanisms, from ion-by-ion to nanoparticle/nanocrystal attachment, in stalagmites from the tropical island of Atiu (South Pacific). Changes in solution stoichiometry and organic matter content result in the development of two columnar fabrics that are common elsewhere in settings characterized by seasonal contrast. A porous columnar fabric, characterized by intracrystalline micro and nanoporosity grows via a non-classical pathway through amorphous calcium carbonate (ACC) nanoparticles (∼2–4 nm in diameter) and calcite nanocrystal attachment. Despite subsequent transformation of nanoparticles/crystals into a large calcite crystal, the porous columnar fabric appears to preserve a δ18O signal that faithfully reflects that of the parent fluid via quasi-equilibrium fractionation. Furthermore, the porous fabric shows random and fuzzy lateral distributions of Sr, another hydrological proxy, yet this element's incorporation follows equilibrium partitioning. The chemical properties of compact columnar fabrics, which appear to grow by classical ion-by-ion attachment, may not directly reflect those of the original depositional environment because of degassing, the presence of growth inhibitors (such as Na) and very early diagenetic modifications. Columnar porous calcite fabrics that formed through non-classical pathways in other settings may faithfully record the original properties of the parent drip water, whereas compact fabrics that formed through classical pathways elsewhere may not. It is concluded that the study of fabrics at the nano-scale is a necessary complement to speleothem research to identify the influence of crystallization pathways on the accuracy of proxy data.

Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.

The mineralocorticoid receptor (MR) is a member of the steroid receptor family and acts as a ligand-dependent transcription factor. In addition to its classical effects on water and electrolyte balance, its involvement in the pathogenesis of cardiovascular and renal diseases has been the subject of research for several years. The molecular basis of the latter has not been fully elucidated, but an isolated increase in the concentration of the MR ligand aldosterone or MR expression does not suffice to explain long-term pathologic actions of the receptor. Several studies suggest that MR activity and signal transduction are modulated by the surrounding microenvironment, which therefore plays an important role in MR pathophysiological effects. Local changes in micromilieu, including hypoxia, ischemia/reperfusion, inflammation, radical stress, and aberrant salt or glucose concentrations affect MR activation and therefore may influence the probability of unphysiological MR actions. The surrounding micromilieu may modulate genomic MR activity either by causing changes in MR expression or MR activity; for example, by inducing posttranslational modifications of the MR or novel interaction with coregulators, DNA-binding sites, or non-classical pathways. This should be considered when developing treatment options and strategies for prevention of MR-associated diseases.

Study on the efficacy of amorphous calcium carbonate as a consolidant for calcareous matrix

The popular involvement of amorphous calcium carbonate (ACC) in organisms, usually via a complicated non-classical crystallization pathway, has aroused interest in the scientific community. In recent years, a lot of work has been carried out for the preparation and application of ACC. In this paper, the effectiveness of ACC for the consolidation of calcareous matrix was evaluated. ACC was synthesized through direct carbonation of calcium oxide in ethanol and was introduced into simulated samples as consolidant. A comprehensive study for the assessment of protective effect was carried out by testing surface strength, chromaticity, compressive strength, water vapor permeability, water absorption and freezing–thawing resistance. The results showed that the addition of ACC could significantly improve the surface strength, compressive strength and weatherability of treated samples, while it had only a slight influence on color difference and water vapor permeability. It was confirmed that ACC could connect the loose calcite particles by ‘spot welding’ through heterogeneous nucleation and growth processes. As a consolidant, it demonstrated its merits in this study and could be proposed as an alternative for the protection of weathered calcareous stones.

THE MOLECULAR MECHANISM OF PYROPTOSIS AND ITS RELATED DISEASES

Cells are the basic unit of life, and cell death plays an important role in the body’s metabolism, the occurrence and development of diseases. Pyroptosis is a form of programmed cell death. Pyroptosis is significantly different from other cell death methods (such as apoptosis, necrosis, etc.) in morphological characteristics, occurrence mechanism, and mechanism of action. When a cell undergoes pyroptosis, the nucleus condenses to form a pyroptotic body, numerous pores appear in the cell membrane, the cell swells and ruptures, releasing its contents. Caspase family is a homologous and structurally similar proteolytic enzyme in cytoplasm, which selectively recognizes and cleaves peptide bonds behind downstream target aspartic acid residues. Canspase 1,4,5,11 can induce pyroptosis through different pathways. Besides caspases, gasdermin also plays an important role in pyroptosis. Gasdermins (GSDMs) are a family of functionally diverse proteins expressed in a variety of cell types and tissues. The Gasdermin family includes 6 members, of which gasdermin D is the executor of pyroptosis. Upon cleavage by activated capsese, gasdermen D can be divided into N and C segments. Among them, the N fragment can form pores in the cell membrane, leading to cell swelling, rupture, outflow of cytokines and other contents, triggering the body’s immune response, and leading to pyroptosis. The occurrence of pyroptosis can be divided into the classical pathway and the non-classical pathway. The classical pathway mainly depends on caspase-1, while the non-canonical pathway depends on the activation of Caspase-4/5/11. In addition, there are uncommon Caspase-3/8- mediated pathway and Granzyme-mediated pathway. As a way of cell death, pyroptosis is inextricably linked to disease. Inflammasomes and cytokines produced in the process of pyroptosis can trigger an inflammatory response in the body, and an excessive inflammatory response can lead to diseases, such as infectious diseases, neurological diseases, and tumors. In infectious diseases, pyroptosis is closely related to the infection of a variety of bacteria, fungi and viruses, and PAMPs and LPS can be recognized by corresponding inflammasomes and caspases, respectively, and activate the downstream pyroptotic pathways. Pathogen infection is the main way to induce pyroptosis. In cardiovascular diseases, a high-fat environment can induce an increase in reactive oxygen species (ROS), trigger endothelial cell pyroptosis, and exacerbate the development of atherosclerosis (AS). In the nervous system, cell death is involved in the pathogenesis of the progression of degenerative diseases of the central nervous system, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. In terms of tumors, pyroptosis can inhibit the occurrence and development of tumors, and at the same time, as a pro-inflammatory death, pyroptosis can form a microenvironment suitable for tumor cell growth, thereby promoting tumor growth.

Nonclassical Nucleation of Zinc Oxide from a Physically Motivated Machine-Learning Approach

Observing nonclassical nucleation pathways remains challenging in simulations of complex materials with technological interests. This is because it requires very accurate force fields that can capture the whole complexity of their underlying interatomic interactions and an advanced structural analysis able to discriminate between competing crystalline phases. Here, we first report the construction and particularly thorough validation of a machine-learning force field for zinc oxide interactions using the Physical LassoLars Interaction Potentials approach which allows us to be predictive even for high-temperature dynamical systems such as ZnO melt. Then, we carried out several types of crystallization simulations and followed the formation of ZnO crystals with atomistic precision. Our results, which were analyzed using a data-driven approach based on bond order parameters, demonstrate the presence of both prenucleation clusters and two-step nucleation scenarios, thus retrieving seminal predictions of nonclassical nucleation pathways made on much simpler models. Dedicated calculations of high-temperature ZnO free energy within a newly developed automated nonequilibrium thermodynamic integration method revealed the existence of a thermodynamic bias for the predicted nonclassical nucleation scenarios.

Organic Crystal Growth: Hierarchical Self-Assembly Involving Nonclassical and Classical Steps

Organic crystal nucleation and growth are complex processes that often do not fit into the framework of the existing crystallization theories. We investigated a crystal growth mechanism of an organic dye, perylene diimide, using high-resolution cryogenic transmission electron microscopy and optical spectroscopy. The elucidated mechanism involves classical (monomer attachments) and nonclassical pathways, exhibiting a self-assembly sequence where all steps are interconnected. It starts from the assembly of molecular π-stacks that are initially disordered. They gradually optimize their structure, rigidify, and interact to form crystalline domains. The latter further evolve via the addition of individual molecules, and crystal fusion (via oriented attachment). All the observed supramolecular transformations are connected and follow a clear hierarchy starting from the molecular-scale interactions. The elucidation of the complex pathway of organic crystallization as a series of coordinated supramolecular transformations at multiple scales conceptually advances the understanding of order evolution in organic matter.

Nonclassical crystallization of zinc carbonate hydroxide hydrate nanofilm mediated by calcium ions

To satisfy the demand of zinc oxide (ZnO) with advanced muti-functional properties, significant efforts have been made in synthesizing ZnO with various structure and morphology. In particular, hydrothermal method has attracted considerable attentions, in which Zn4CO3(OH)6·H2O (ZCHH) is commonly found as a metastable precursor. However, the formation and crystallization mechanisms of ZCHH are still lacking and urgently needed. In the present study, the crystallization pathway of ZCHH was systematically investigated, and the results demonstrate that the amorphous zinc carbonate (AZC) was an even more unstable precursor. AZC nanoparticles typically aggregated to form one-dimensional (1D) ZCHH nanorods, however, two-dimensional (2D) ZCHH nanofilms were obtained in the presence of a certain concentration of calcium ion. The results suggest that calcium ions could promote the partial dissolution of AZC and facilitate the aggregation of AZC nanoparticles to form crystalline nanofilm. Moreover, 2D ZnO nanofilms could be obtained by heat treatment of the ZCHH nanofilms. The calcium ion mediated nonclassical crystallization pathway provides inspiration for fabrication of ZnO with controlled morphology and offers new opportunities for inorganic regulated material synthesis.