Background

Saliva (oral fluids) is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer) is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear.

Methodology/principal findings

In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs) Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland.

Conclusions

Taken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.

Compositional engineering has been used to overcome difficulties in fabricating high-quality phase-pure formamidinium perovskite films together with its ambient instability. However, this comes alongside an undesirable increase in bandgap that sacrifices the device photocurrent. Here we report the fabrication of phase-pure formamidinium-lead tri-iodide perovskite films with excellent optoelectronic quality and stability. Incorporation of 1.67 mol% of 2D phenylethylammonium lead iodide into the precursor solution enables the formation of phase-pure formamidinium perovskite with an order of magnitude enhanced photoluminescence lifetime. The 2D perovskite spontaneously forms at grain boundaries to protect the formamidinium perovskite from moisture and suppress ion migration. A stabilized power conversion efficiency (PCE) of 20.64% (certified stabilized PCE of 19.77%) is achieved with a short-circuit current density exceeding 24 mA cm^-2 and an open-circuit voltage of 1.130 V, corresponding to a loss-in-potential of 0.35 V, and significantly enhanced operational stability.

Metal halide perovskite solar cells (PSCs) are infamous for their batch-to-batch and lab-to-lab irreproducibility in terms of stability and performance. Reproducible fabrication of PSCs is a critical requirement for market viability and practical commercialization. PSC irreproducibility plagues all levels of the community; from institutional research laboratories, start-up companies, to large established corporations. In this work, the critical function of atmospheric humidity to regulate the crystallization and stabilization of formamidinium lead triiodide (FAPbI₃) perovskites is unraveled. It is demonstrated that the humidity content during processing induces profound variations in perovskite stoichiometry, thermodynamic stability, and optoelectronic quality. Almost counterintuitively, it is shown that the presence of humidity is perhaps indispensable to reproduce phase-stable and efficient FAPbI₃-based PSCs.

Manipulation of grain boundaries in polycrystalline perovskite is an essential consideration for both the optoelectronic properties and environmental stability of solar cells as the solution-processing of perovskite films inevitably introduces many defects at grain boundaries. Though small molecule-based additives have proven to be effective defect passivating agents, their high volatility and diffusivity cannot render perovskite films robust enough against harsh environments. Here we suggest design rules for effective molecules by considering their molecular structure. From these, we introduce a strategy to form macromolecular intermediate phases using long chain polymers, which leads to the formation of a polymer-perovskite composite cross-linker. The cross-linker functions to bridge the perovskite grains, minimizing grain-to-grain electrical decoupling and yielding excellent environmental stability against moisture, light, and heat, which has not been attainable with small molecule defect passivating agents. Consequently, all photovoltaic parameters are significantly enhanced in the solar cells and the devices also show excellent stability.

Postfabrication surface treatment strategies have been instrumental to the stability and performance improvements of halide perovskite photovoltaics in recent years. However, a consensus understanding of the complex reconstruction processes occurring at the surface is still lacking. Here, we combined complementary surface-sensitive and depth-resolved techniques to investigate the mechanistic reconstruction of the perovskite surface at the microscale level. We observed a reconstruction toward a more PbI₂-rich top surface induced by the commonly used solvent isopropyl alcohol (IPA). We discuss several implications of this reconstruction on the surface thermodynamics and energetics. Particularly, our observations suggest that IPA assists in the adsorption process of organic ammonium salts to the surface to enhance their defect passivation effects.

Conventional epitaxy of semiconductor films requires a compatible single crystalline substrate and precisely controlled growth conditions, which limit the price competitiveness and versatility of the process. We demonstrate substrate-tolerant nano-heteroepitaxy (NHE) of high-quality formamidinium-lead-tri-iodide (FAPbI₃) perovskite films. The layered perovskite templates the solid-state phase conversion of FAPbI₃ from its hexagonal non-perovskite phase to the cubic perovskite polymorph, where the growth kinetics are controlled by a synergistic effect between strain and entropy. The slow heteroepitaxial crystal growth enlarged the perovskite crystals by 10-fold with a reduced defect density and strong preferred orientation. This NHE is readily applicable to various substrates used for devices. The proof-of-concept solar cell and light-emitting diode devices based on the NHE-FAPbI₃ showed efficiencies and stabilities superior to those of devices fabricated without NHE.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19846-y .