Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms.

Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.

Green Light from Red-Emitting Nanocrystals: Broadband, Low-Threshold Lasing from Colloidal Quantum Shells in Optical Nanocavities.

Spherical semiconductor nanoplatelets, known as quantum shells (QSs), have captured significant interest for their strong suppression of Auger recombination, which leads to long multiexciton lifetimes and wide optical gain bandwidth. Yet, the realization of benefits associated with the multiexciton lasing regime using a suitably designed photonic cavity remains elusive. Here, we demonstrate broadly tunable lasing from close-packed films of CdS/CdSe/CdS QSs deposited over nanopillar arrays on Si substrates. Wide spectral tuning of the stimulated emission in QSs with a fixed bandgap value was achieved by engaging single exciton (λX ∼ 634 nm), biexciton (λBX ∼ 627 nm), and multiple exciton (λMX ∼ 615-565 nm) transitions. The ensemble-averaged gain threshold of ∼ 2.6 electron-hole pairs per QS particle and the low photonic cavity fluence threshold of ∼4 µJ/cm2 were attributed to Auger suppression. The tuning of the lasing emission closely aligns with our model predictions achieved by varying the array period while preserving mode confinement and quality (Q) factors. These results mark a notable step toward the development of colloidal nanocrystal lasers.

Highly Emissive Zero-Dimensional Cesium Lead Iodide Perovskite Nanocrystals with Thermally Activated Delayed Photoluminescence.

We utilized a modified reverse-microemulsion method to develop highly emissive and photostable zero-dimensional (0D) Cs4Pb(Br1-xIx)6 perovskite nanocrystals (PNCs). We employed single-particle photoluminescence (PL) spectroscopy to explore blinking statistics and demonstrate single-photon emission from individual PNCs. Low-temperature blinking and photon correlation studies revealed a transition from single- to multiphoton emission with progressively longer "delayed" PL components, reaching ∼70 ns at room temperature and representing a distinctive behavior to previously known iodide PNCs. Such thermally activated PL emission is explained by the existence of defect-related "reservoir" states, feeding back into the PNC's emissive state and providing multiple photons within a single excitation cycle. This work establishes a new member in the 0D class of perovskite materials, studies its photophysical properties, and reveals its potential for future optoelectronic applications.

The Impact of Household Migration on the Intergenerational Educational Mobility: Based on the Perspective of Adolescent Development.

Improving intergenerational mobility is crucial for enhancing the efficacy of human capital, ensuring social vitality, and supporting sustainable long-term economic growth. Based on the China Labor-force Dynamic Survey (CLDS) of 2014, this paper empirically examines the effect of adolescent household migration on intergenerational educational mobility by using a fixed-effect model. The study found that: (1) Household migration in the adolescent period significantly improves intergenerational educational mobility. (2) The quality and quantity of education of offspring are the channels through which household migration improves the intergenerational educational mobility of the household. (3) There are significant differences between urban and rural areas, gender, and household resource allocation in the effect of adolescent household migration on intergenerational educational mobility. As the majority of poor households are unable to improve intergenerational mobility through migration due to its costs and institutional barriers, this paper suggests that the government should concentrate on reducing regional disparities in educational resources, advancing rural education reform, and enhancing social security.

Tumor cell-released LC3-positive EVs promote lung metastasis of breast cancer through enhancing premetastatic niche formation.

Most breast cancer-related deaths are caused by metastasis in vital organs including the lungs. Development of supportive metastatic microenvironments, referred to as premetastatic niches (PMNs), in certain distant organs before arrival of metastatic cells, is critical in metastasis. However, the mechanisms of PMN formation are not fully clear. Here, we demonstrated that chemoattractant C-C motif chemokine ligand 2 (CCL2) could be stimulated by heat shock protein 60 (HSP60) on the surface of murine 4 T1 breast cancer cell-released LC3+ extracellular vesicles (LC3+ EVs) via the TLR2-MyD88-NF-κB signal cascade in lung fibroblasts, which subsequently promoted lung PMN formation through recruiting monocytes and suppressing T cell function. Consistently, reduction of LC3+ EV release or HSP60 level or neutralization of CCL2 markedly attenuated PMN formation and lung metastasis. Furthermore, the number of circulating LC3+ EVs and HSP60 level on LC3+ EVs in the plasma of breast cancer patients were positively correlated with disease progression and lung metastasis, which might have potential value as biomarkers of lung metastasis in breast cancer patients (AUC = 0.898, 0.694, respectively). These findings illuminate a novel mechanism of PMN formation and might provide therapeutic targets for anti-metastasis therapy for patients with breast cancer.

Immune escaping of the novel genotypes of human respiratory syncytial virus based on gene sequence variation.

Purpose: Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients. Methods: The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated. Results: The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1ß in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1ß in the first serum samples from patients with ON1 compared to those with BA9 of subtype B. Conclusions: Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.

The Effects of Platelet-Rich and Platelet-Poor Plasma on Biological Characteristics of BM-MSCs In Vitro.

Platelet-rich plasma (PRP) and its byproduct platelet-poor plasma (PPP) are rich sources of cytokines in tissue damage repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have received more and more attention for their ability to treat multiple diseases. The purpose of our study was to investigate the biologic action of PPP and PRP on BM-MSCs. The adipogenic potential of BM-MSCs revealed no obvious change, but the osteogenic ability of BM-MSCs was enhanced after treated with PRP. CCK8 assays and cell colony formation assays showed that PRP promoted cell proliferation, while this effect of PPP was not obvious. No obvious difference was found in cell cycle and apoptosis of BM-MSCs between PRP and PPP treatment. Expression of ß-galactosidase, a biological marker of senescence, was decreased upon PRP treatment which indicated that PRP provided significant protection against cellular senescence. The migratory capacity of BM-MSCs was detected by scratch and transwell assays. The results indicated that PRP could affect the migration ability of BM-MSCs. From immunofluorescence detection and western blot, we demonstrated that the level of epithelial-mesenchymal transition-related proteins was changed and several pluripotency marker genes, including Sox2, Sall4, Oct4, and Nanog, were increased. Finally, the expression of the key signal pathway such as PI3K/AKT was examined. Our findings suggested that PRP promoted cell migration of BM-MSCs via stimulating the signaling pathway of PI3K/AKT.

Interface Matters: Enhanced Photoluminescence and Long-Term Stability of Zero-Dimensional Cesium Lead Bromide Nanocrystals via Gas-Phase Aluminum Oxide Encapsulation.

Cesium lead halide perovskite nanocrystals (PNCs), while possessing facile chemical synthesis routes and high photoluminescence (PL) properties, are still challenged by issues of instability and degradation. Although atomic layer deposition (ALD) of metal oxides has been one of the common encapsulation approaches for longer term stability, its application inevitably resulted in severe loss of emission efficiency and at times partial loss of structural integrity of perovskites, creating a bottleneck in its practical viability. We demonstrate a nondestructive modified gas-phase technique with codeposition of both precursors trimethylaluminum and water to dramatically enhance the PL emission in zero-dimensional (0D) Cs4PbBr6 PNCs via alumina encapsulation. X-ray photoelectron spectroscopy analysis of Cs4PbBr6 films reveals the alumina deposition to be accompanied by elemental composition changes, particularly by the reduction of the excessive cesium content. Ab initio density functional theory simulations further unfold that the presence of excess Cs on the surface of PNCs leads to decomposition of structural [PbBr6]4- octahedra in the 0D perovskite lattice, which can be prevented in the presence of added hydroxyl groups. Our study thus unveils the pivotal role of the PNC surface composition and treatment in the process of its interaction with metal oxide precursors to control the PL properties as well as the stability of PNCs, providing an unprecedented way to use the conventional ALD technique for their successful integration into optoelectronic and photonic devices with improved properties.

Adipose-derived mesenchymal stem cells and extracellular vesicles confer antitumor activity in preclinical treatment of breast cancer.

Both antitumor and protumor property of mesenchymal stem cells (MSCs) have been demonstrated. We hypothesize that this contradiction is due to the heterogeneity of MSC subsets and that extracellular vesicles (EVs) from distinct MSC subsets can transfer the corresponding antitumor activities. Here we evaluated the antitumor activities of two subsets of adipose-derived mesenchymal stem cells (ADSCs) and ADSC-derived EVs (ADSC-EVs) in immunocompetent syngeneic mouse models of breast cancer. We identified CD90high and CD90low ADSC subsets and demonstrated that CD90high ADSCs could be converted into CD90low ADSCs by stimulation with LPS. CD90low ADSCs and its derived EVs significantly inhibited tumor growth in tumor-bearing mice. Benefit of tumor control were associated with decreased tumor cell proliferation and migration, and enhanced tumor cell apoptosis mediated by ADSC-EVs. Antioncogenic miRNA-16-5p loaded CD90low ADSC-EVs further significantly enhanced antitumor activities. Taken together, this study represents the first attempt to apply our newly identified antitumor ADSCs and its derived EVs in preclinical treatment of breast cancer. This study also provides the evidence that EVs can serve as a novel and effective therapeutics or drug delivery vesicle. This new therapeutic approach could be potentially applicable to breast cancer and many other types of cancer.

Dynamical Interconversion between Excitons and Geminate Charge Pairs in Two-Dimensional Perovskite Layers Described by the Onsager-Braun Model.

Time-resolved photoluminescence (PL) and femtosecond transient absorption (TA) spectroscopy are employed to study the photoexcitation dynamics in a highly emissive two-dimensional perovskite compound (en)4Pb2Br9·3Br with the ethylene diammonium (en) spacer. We find that while the PL kinetics is substantially T-dependent over the whole range of studied temperatures T ∼ 77-350 K, the PL quantum yield remains remarkably nearly T-independent up to T ∼ 280-290 K, appreciably decreasing only at higher temperatures. Considerable differences are also revealed between the TA spectra and the responses to the excitation power at low and at room temperatures. Numerical solutions of Onsager-Braun-type kinetic-diffusion equations illustrate that the salient features of the experimental observations are consistent with the picture of a T-dependent dynamic interplay between tightly bound emissive excitons and larger-size, loosely bound, nonemissive geminate charge pairs arising already at earlier relaxation times. The geminate pairs play the role of "reservoir" states providing a delayed feeding into the emitting excitons, thus giving rise to the longer-time PL decay components and accounting for a stable PL output at lower temperatures. At higher temperatures, the propensity for thermal dissociation of excitons and bound pairs increases, leading subsequently to the precipitous decrease of the PL.

Delayed Photoluminescence and Modified Blinking Statistics in Alumina-Encapsulated Zero-Dimensional Inorganic Perovskite Nanocrystals.

We demonstrate enhancement of the photoluminescence (PL) properties of individual zero-dimensional (0D) Cs4PbBr6 perovskite nanocrystals (PNCs) upon encapsulation by alumina using an appropriately modified atomic layer deposition method. In addition to the increased PL intensity and improved long-term stability of encapsulated PNCs, our single-particle studies reveal substantial changes in the PL blinking statistics and the persistent appearance of the long-lived, "delayed" PL components. The blinking patterns exhibit a modification from the fast switching between fluorescent ON and OFF states found in bare PNCs to a behavior with longer ON states and more isolated OFF states in alumina-encapsulated PNCs. Controlled exposure of 0D nanocrystals to moisture suggests that the observed PL lifetime changes may be related to water-induced "reservoir" states that allow for longer-lived charge storage with subsequent back-feeding into the emissive states. Viable encapsulation of PNCs with metal oxides that can preserve and even enhance their PL properties can be utilized in the fabrication of extended structures on their basis for optoelectronic and photonic applications.

Mesenchymal stem cell­derived extracellular vesicles promote the in vitro proliferation and migration of breast cancer cells through the activation of the ERK pathway.

Mesenchymal stem cells (MSCs) have been demonstrated to be involved in tumor progression and the modulation of the tumor microenvironment, partly through their secretome. Extracellular vesicles (EVs) are membranous nanovesicles secreted by multiple types of cells and have been demonstrated to mediate intercellular communication in both physiological and pathological conditions. However, numerous questions still remain regarding the underlying mechanisms and functional consequences of these interactions. The purpose of this study was to investigate the effects of human umbilical cord mesenchymal stem cell­derived EVs (hUC­MSC­EVs) on the proliferation, migration and invasion of human breast cancer cells. We successfully generated and identified hUC­MSCs and hUC­MSC­EVs which were used in this study. The results revealed that treatment of the MDA­MB­231 and MCF­7 human breast cancer cells with medium containing hUC­MSC­EVs significantly enhanced the proliferation, migration and invasion of the cells in vitro. Treatment of the cells with medium containing hUC­MSC­EVs also reduced E­cadherin expression and increased N­cadherin expression, thus promoting the epithelial­mesenchymal transition (EMT) of the breast cancer cells. Treatment of the breast cancer cells with extracellular signal­regulated kinase (ERK) inhibitor prior to the interaction with hUC­MSC­EVs significantly reversed the enhanced proliferation, migration and invasion, as well as the EMT of the breast cancer cells induced by the hUC­MSC­EVs. On the whole, these data indicate that hUC­MSC­EVs promote the invasive and migratory potential of breast cancer cells through the induction of EMT via the ERK pathway, leading to malignant tumor progression and metastasis. Taken together, the findings of this study suggest that targeting pathways to reverse EMT may lead to the development of novel therapeutic approaches with which to combat breast cancer.

Tunable Water-Soluble Supramolecular Polymers by Visible-Light-Regulated Host-Guest Interactions.

The development of artificial self-assembling systems with dynamic photo-regulation features in aqueous solutions has drawn great attention owing to the potential applications in fabricating elaborate biological materials. Here we demonstrate the fabrication of water-soluble cucurbit[8]uril (CB[8])-mediated supramolecular polymers by connecting the fluorinated azobenzene (FAB) containing monomers through host-enhanced heteroternary π-π stacking interactions. Benefiting from the unique visible-light-induced E→Z photoisomerization of the FAB photochromophores, the encapsulation behaviors between the CB[8] macrocycle and the monomers could be regulated upon visible light irradiation, resulting in the depolymerization of such CB[8]-mediated supramolecular polymers.

Effect of idebenone on bone marrow mesenchymal stem cells in vitro.

In recent years, stem cell research has continued to benefit from its crossover with chemistry, particularly the investigation of small molecular drugs modulating specific targets to regulate stem cell fate. Idebenone (IDB) is a yellow crystalline powder that is used in the treatment of chronic cerebrovascular diseases. The objective of the present study was to examine whether IDB had an influence on bone marrow­derived mesenchymal stem cells (BMSCs) extracted from the bone marrow of Sprague­Dawley rats. The effects of IDB on cell proliferation, cell cloning and migration were investigated. Cell cycle, apoptosis, DAPI nuclear staining and senescence­associated ß­galactosidase (SA­ß­gal) staining were also examined. The results revealed that IDB at suitable concentrations enhanced cell cloning capacity, promoted the proliferation of BMSCs, delayed cellular senescence, and inhibited cell apoptosis and migration. Western blot analysis indicated that IDB increased the expression of B­cell lymphoma 2 (Bcl­2), signal transducer and activator of transcription­3, Nanog, octamer­binding transcription factor 4, E­cadherin, proliferating cell nuclear antigen, cyclinD1 and cyclinD3, and decreased the expression of Bcl­2­associated X protein, cleaved caspase­3, N­cadherin, vimentin and α­smooth muscle actin. In conclusion, these experiments confirmed that IDB in low doses had no toxic effect and may exert protective effects on BMSCs.