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BackgroundSigmoid colon cancer with spinal metastases is rare in distant metastasis. In addition, the prognosis of colon cancer patients with spinal metastases is extremely poor. In order to find effective therapeutic agents, we need to know the biological characteristics of such patients from related models.MethodsWe collected sigmoid colon cancer tissue from a young female subject who was diagnosed with sigmoid colon cancer with multiple spinal metastases. We successfully established a sigmoid colon cancer organoid using this tissue and investigated drug screening in the patient. HE staining, immunohistochemistry, and DNA sequencing were utilized to compare the biological characteristics between the original tumor and the organoid. Furthermore, we investigated the drug screening of the sigmoid colon cancer organoid in vitro.ResultsA colon cancer organoid from sigmoid colon cancer with spinal metastases was successfully established. The organoid culture maintained the morphological features, histological features, and genomic landscape of the corresponding sigmoid colon cancer cells. Moreover, we performed drug screening tests to evaluate the effects of chemotherapeutic drugs and targeted drugs.ConclusionThe sigmoid colon cancer organoid with spinal metastases was a favorable preclinical model to explore the clinicopathologic characteristics of colon cancer patients with spinal metastases.

Outer membrane vesicles (OMVs) are immunogenic self-adjuvanting vesicles produced by Gram-negative bacteria such as Pseudomonas aeruginosa and Yersinia pseudotuberculosis. While the effects of OMVs on different antigens immune stimulation are not clear. In this study, we constructed recombinant Yersinia pseudotuberculosis ΔlpxL strain,with pBlue-PcrV and pBlue-OprF/I, and then purified ΔlpxL rOMVPcrV (rOMVyp2P)and ΔlpxL rOMVOprF/I (rOMVyp2F) and analyzed its effect on immune response and protection against Pseudomonas aeruginosa PAO1 infection. The results showed that OMV assists in eliciting similar humoral immune responses to PcrV and OprF/I antigens. ΔlpxL rOMVPcrV and ΔlpxL rOMVOprF/I elicited Th1/Th2 balanced immune response, and higher IgM and IgA antibodies.However, there are differences in immune protection for the pulmonary. The survival rate of mice in ΔlpxL rOMVPcrV group was 20%, which was significantly better than that in ΔlpxL rOMVOprF/I group. ΔlpxL OMVPcrV is better cooperation for Pseudomonas immune protection in lung.

IntroductionGastric cancer (GC) is the fifth most common tumor, contributing to the third-highest number of cancer-related deaths. Hypoxia is a major feature of the tumor microenvironment. This study aimed to explore the influence of hypoxia in GC and establish a hypoxia-related prognostic panel.MethodsThe GC scRNA-seq data and bulk RNA-seq data were downloaded from the GEO and TCGA databases, respectively. AddModuleScore() and AUCell() were used to calculate module scores and fractions of enrichment for hypoxia-related gene expression in single cells. Least absolute shrinkage and selection operator cox (LASSO-COX) regression analysis was utilized to build a prognostic panel, and hub RNAs were validated by qPCR. The CIBERSORT algorithm was adopted to evaluate immune infiltration. The finding of immune infiltration was validated by a dual immunohistochemistry staining. The TIDE score, TIS score and ESTIMATE were used to evaluate the immunotherapy predictive efficacy.ResultsHypoxia-related scores were the highest in fibroblasts, and 166 differentially expressed genes were identified. Five hypoxia-related genes were incorporated into the hypoxia-related prognostic panel. 4 hypoxia-related genes (including POSTN, BMP4, MXRA5 and LBH) were significantly upregulated in clinical GC samples compared with the normal group, while APOD expression decreased in GC samples. Similar results were found between cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). A high hypoxia score was associated with advanced grade, TNM stage, N stage, and poorer prognosis. Decreased antitumor immune cells and increased cancer-promoting immune cells were found in patients with high hypoxia scores. Dual immunohistochemistry staining showed high expression of CD8 and ACTA2 in gastric cancer tissue. In addition, the high hypoxia score group possessed higher TIDE scores, indicating poor immunotherapy benefit. A high hypoxia score was also firmly related to sensitivity to chemotherapeutic drugs.DiscussionThis hypoxia-related prognostic panel may be effective in predicting the clinical prognosis, immune infiltrations, immunotherapy, and chemotherapy in GC.

Abstract Background It has been reported that long-chain non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is an oncogene in various cancers, including hepatocellular carcinoma (HCC). We investigated the role and mechanism of ZEB1-AS1 as a competitive endogenous RNA (ceRNA) combined with miR-23c in HCC cell proliferation and invasion. Methods QRT-PCR was used to detect ZEB1-AS1 and miR-23c expressions in HCC tissues and cells. The dual luciferase reporter assay detected the targeted regulation of miR-23c and ZEB1-AS1. We also performed the correlation analysis of their expression in HCC tissues by the Spearman’s correlation analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of hepatoma cells. Cell invasion was assessed by the Transwell assay. Results QRT-PCR results indicated ZEB1-AS1 was upregulated and miR-23c was downregulated in HCC tissues and cell lines. ZEB1-AS1 knockdown hampered the proliferation and invasion of HCC cells. Dual luciferase reporter assay showed that miR-23c is a target of ZEB1-AS1, and ZEB1-AS1 was significantly negatively correlated with the miR-23c expression in HCC tissues. The results of MTT and Transwell assay showed that miR-23c inhibition restored the inhibitory effect of ZEB1-AS1 knockdown on HCC cells proliferation and invasion. Conclusions As a ceRNA, lncRNA ZEB1-AS1 may play a vital role in inhibiting HCC progression through miR-23c, which will provide new clues and theoretical basis for the HCC diagnosis and treatment.

Abstract Although adipose‐derived mesenchymal stem cells (ADMSCs) isolated from patients’ fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless‐electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt‐level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron‐specific genes, and proteins. Most importantly, Ca2+ intracellular influx is observed in these ADMSC‐derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure‐mediated physical‐signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration.

Background: Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated. Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects. Design: Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) and Sirt1 siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways in vivo and in vitro. Results: Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27 ± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NAD+ level in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover, Sirt1 knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers. Conclusion: PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1- dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.

Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.

BackgroundRecent research of clear cell renal cell carcinoma (ccRCC) is focused on the tumor immune microenvironment (TIME). Chromatin accessibility is critical for regulation of gene expression. However, its role in different immunological subtypes of ccRCC based on immune cell infiltration has not been systematically studied.MethodsFive hundred thirty patient data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) were adopted to estimate immune cell infiltration. Twenty-four types of immune cells were evaluated with single-sample Gene Set Enrichment Analysis (ssGSEA). Patients were divided into two clusters based on immune cell infiltration. Systematic chromatin accessibility analysis was conducted based on the two clusters.ResultsWe compared the relative expression of the immune gene signatures among 530 patients of TCGA-KIRC using ssGSEA. Overall survival (OS) analysis revealed 10 types of immune cells were significantly associated with prognosis. Patients were divided into two clusters based on 24 types of immune cell infiltration. Immune cell signals as well as PD-1/PD-L1 signal were higher in cluster 1. Among the two clusters, 2,400 differential peaks were found in TCGA-KIRC Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) data. The distribution of differential peaks and prognosis-related immune cells in 23 chromosomes are essentially the same. There is no peak distribution downstream. The proportion of peaks upstream of the 5’ transcription start site decreases, and both sides of binding regions of the TSS 0.1-1 kb becomes smaller. Enrichment analysis of GO and KEGG of these differential peaks showed that they are remarkably related to the immune regulation in tumor microenvironment. Known motifs and de novo motifs were found by linking motif annotations to different peaks. Survival analysis of related motif transcription factors were prognostic. The GSEA enrichment analysis showed that high SP1 expression positively correlates with TGF-beta signaling and inflammatory response, while negatively correlates with TNF-alpha signaling via NFKB. High KLF12 expression negatively correlates with interferon gamma response, IL2-STAT5 signaling, TNF-alpha signaling via NFKB, IL6-JAK-STAT3 signaling.ConclusionThe abnormality of chromatin accessibility may play an important regulatory role in ccRCC immunity.

Oxidized low-density lipoprotein (oxLDL)-induced endothelium injury promotes the development of atherosclerosis. It has been reported that homoplantaginin, a flavonoid glycoside from the traditional Chinese medicine Salvia plebeia R. Br., protected vascular endothelial cells by inhibiting inflammation. However, it is undetermined whether homoplantaginin affects atherosclerosis. In this study, we evaluated the effect of homoplantaginin and its derivative dihydrohomoplantagin on oxLDL-induced endothelial cell injury and atherosclerosis in apoE-/- mice. Our results showedthat both dihydrohomoplantagin and homoplantaginin inhibited apoptosis and the increased level of ICAM-1 and VCAM-1 in oxLDL-stimulated HUVECs and the plaque endothelium of apoE-/- mice. Additionally, both of them restricted atherosclerosis development of apoE-/- mice. Mechanistic studies showed that oxLDL-induced the increase in ROS production, phosphorylation of ERK and nuclear translocation of NF-κB in HUVECs was significantly inhibited by the compounds. Meanwhile, these two compounds promoted Nrf2 nuclear translocation and increased the anti-oxidation downstream HO-1 protein level in HUVECs and plaque endothelium. Notably, knockdown of Nrf2 by siRNA abolished the cell protective effects of compounds and antagonized the inhibition effects of them on ROS production and NF-κB activation in oxLDL-stimulated HUVECs. Collectively, dihydrohomoplantagin and homoplantaginin protected VECs by activating Nrf2 and thus inhibited atherosclerosis in apoE-/- mice.

The current study examined a multiple mediator model based on the control-value theory. A sample of 433 Chinese junior middle school students participated in questionnaires assessing teacher-student relationships (TSRs), academic emotions, academic value (AV), and academic self-efficacy (ASE). English test scores were collected as an indicator of students' English academic performance. The results indicated the following: (a) for academic enjoyment, the TSR has an effect on academic achievement through the chain intermediary of AV and ASE; (b) for academic relaxation, the TSR has an effect on English academic achievement through the single intermediary of academic relaxation and the chain intermediary of AV, ASE, and academic relaxation; (c) for academic anxiety, the TSR has an effect on English academic achievement through the single intermediary of AV, the single intermediary of academic anxiety, and the chain intermediary of AV, ASE, and academic anxiety; (d) for academic boredom, the TSR has an effect on English academic achievement through the single intermediary of academic boredom. These findings enrich the relevant research on the control-value theory and provide important insights for improving students' English academic achievement.

Emerging evidence suggests that fibromodulin (FMOD), an extracellular matrix protein, is associated with cancer, and yet little is known about the regulation of FMOD expression and its role in cancer metastasis. Aspirin, a classic anti-inflammatory drug, has been indicated to offer anticancer benefits, but its action targets and mechanisms remain obscure. In the present study using cell lines, animal model and database analysis, we show that FMOD is crucial for breast cancer cell migration and invasion (BCCMI) via activation of ERK; expression of FMOD is regulated positively by the Wnt/β-catenin pathway, wherein the β-catenin/TCF4/LEF1 complex binds the FMOD promoter to transcribe FMOD. Aspirin inhibits BCCMI by attenuating Wnt/β-catenin signaling and suppressing FMOD expression via inhibiting deacetylation of β-catenin by histone deacetylase 6 (HDAC6) leading to β-catenin phosphorylation and cytoplasmic degradation. Moreover, expression of the transcriptional complex components β-catenin/TCF4/LEF1 is upregulated by the Wnt/β-catenin pathway, constituting positive feedback loops that amplify its signal output. Our findings identify a critical role of FMOD in cancer metastasis, reveal a mechanism regulating FMOD transcription and impacting tumor metastasis, uncover action targets and mechanism for the anticancer activity of Aspirin, and expand the understanding of the Wnt/β-catenin pathway and tumor metastasis, which are valuable for development of cancer therapeutics.

Senescence of vascular endothelial cells promotes endothelial dysfunction and contributes to the progression of cardiovascular diseases. It is imperative to explore effective methods to suppress endothelial senescence. Herein, we found flavonoids including quercetin, puerarin and troxerutin, which exist in normal diet and extracted from traditional herbs, delayed d-glucose-induced endothelial senescence and restored endothelial functions. In the process, d-glucose amplified endogenous reactive oxygen species (ROS) level and subsequently promoted NLRP3 inflammasome activation. However, these alterations were reversed by flavonoids. Meanwhile, clearance of ROS or interference of NLRP3 function by specific siRNA attenuated high glucose-induced senescence but advanced the anti-senescent impact of flavonoids. On the contrary, the preventive effect of flavonoids on senescence was disturbed once NLRP3 inflammasome was overactivated. Our studies suggest that flavonoids can inhibit high glucose-induced endothelial premature senescence by suppressing NLRP3 inflammasome activity, which may be a useful therapeutic strategy to alleviate endothelial senescence-related vascular diseases.

The rate of neuronal differentiation of bone marrow stromal cells (BMSCs) in vivo is very low; therefore, it is necessary to elevate the number of BMSC-derived neurons to cure neurodegenerative diseases. We previously reported that tricyclodecane-9-yl-xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), induced BMSCs to differentiate into neuron-like cells in vitro. However, the neuronal type is not clear, and it is still unknown whether these neuron-like cells possess physiological properties of functional neurons and whether they can contribute to the recovery of neuron dysfunction. To answer these questions, we investigated their characteristics by detecting neuronal function-related neurotransmitters and calcium image. The results showed that these cells exhibited functional cholinergic neurons in vitro. Transplantation of these cholinergic neuron-like cells promoted the recovery of spinal cord-injured mice, and they were more effective than BMSCs. The number of cholinergic neurons was increased after injection with BMSC-derived cholinergic neuron-like cells, indicating their high differentiation rate in vivo. Moreover, the proportion of cholinergic neurons in host cells and secretion of acetylcholine were increased, and preservation of neurofilament was also observed in the lesion of mice implanted with BMSC-derived neurons, suggesting the neuronal protection of BMSC-derived neurons. Our findings provide both a simple method to induce the differentiation of BMSCs into cholinergic neuron-like cells and a putative strategy for the therapy of spinal cord injuries.

The influences of an NH4F additive content and calcination time on the morphological evolution of α-Al2O3 were investigated by using commercial γ-Al2O3 precursor as raw material. The results showed that the morphological evolution of α-Al2O3 was highly related to the addition of NH4F, the additive content, and the calcination time. Square-like α-Al2O3 powders with a primary crystal size of ~200 nm were formed from the milled γ-Al2O3 precursor with 1 wt.% NH4F at 1300°C for 2 h, whereas round cake-like, hexagonal platelets, slenderlike, and other irregularly shaped α-Al2O3 pieces in the size range of 0.2-2 μm were synthesized from the milled γ-Al2O3 precursor with 20 wt.% NH4F addition under the same calcination. Both morphological regularity and particle size distribution of α-Al2O3 were greatly facilitated by increasing the calcination time from 2 to 5 h. The addition of NH4F may lead to an alteration of the α-Al2O3 growth process by a change in the scale of the developing microstructure. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect. [ABSTRACT FROM AUTHOR]

Mobile Ad-hoc Networks (MANETs) are considered as the most promising terminal networks in future wireless communications and characterized by flexibility, fast and easy deployment, which make them an interesting technology for various applications. Group communication is one of the main concerns in MANETs. To provide the secure group communication in wireless networks, a group key is required so that efficient symmetric encryption can be performed. In this paper, we propose a constant-round group key agreement scheme to enable secure group communications, which adopts the Identity Based Broadcast Encryption (IBBE) methodology. When a new Ad-hoc network is constructed, the suggested scheme requires no message exchange to establish a group key if the receivers' identities are known to the broadcaster, which is an advantage that outperforms most of the existing key agreement schemes. The proposed scheme can build a new group and establish a new group key with ease when member joins or leaves. In addition, our scheme is efficient in computation and only one bilinear pair computation is required for group members to obtain his/her session key. A highlight property of the scheme is that communication cost remains unchanged as group size grows. Furthermore, we show that the new scheme is proved secure without random oracle. Thus, the scheme can not only meet security demands of larger mobile Ad-hoc networks but also improve executing performance. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that the senescence of vascular endothelial cells (VECs) has critical roles in the pathogenesis of vascular dysfunction. Finding important factors that regulate VEC senescence will help provide novel therapeutic strategies for vascular disorders. Previously, we found that integrin β4 was involved in VEC senescence. However, the mechanism underlying VEC senescence mediated by integrin β4 remains poorly understand. In this study, we used a mouse in vivo model and showed that the level of integrin β4 in the endothelium of mouse thoracic aorta was increased during natural aging and atherosclerosis. Furthermore, we found that H-ras, caveolin-1, and AP-1 were implicated in the senescent signal pathway mediated by integrin β4 in human umbilical vein ECs (HUVECs). Knockdown of integrin β4 could attenuate HUVEC senescent features, including increased interleukin-8 (IL-8) release and decreased endothelial nitric oxide synthase (eNOS) and NO levels and mitochondrial membrane potential in vitro. Our findings provide new clues illustrating the mechanism of VEC senescence. Integrin β4 might be a potential target for therapy in cardiovascular diseases. J. Cell. Physiol. 225: 673-681, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Recently, the wide application of upconversion nanoparticles (UCNPs) in the field of bioimaging has raised the requirement of biocompatibility. Current cytocompatibility studies on UCNPs mainly focus on cancer cells; however, their potential effects on normal cells are rarely addressed. Herein, the cellular effects of a trace amount of ligand-free NaYF4:Yb/Er nanocrystals on the differentiation of rat bone mesenchymal stem cells (rBMSCs) were investigated. First, due to their excellent upconversion fluorescent properties, the cellular uptake of ligand-free NaYF4:Yb/Er nanocrystals was confirmed by confocal laser scanning microscopy, and a homogeneous cytoplasmic distribution was imaged. Second, the viability of the rBMSCs cultured with a series of concentrations of nanoparticles (0, 30, 300, and 3000 ng ml−1) was evaluated, and a dose threshold was determined. Third, the effects of ligand-free NaYF4:Yb/Er nanocrystals on the osteogenesis of the rBMSCs were intensively characterized. The alkaline phosphatase activity assay, quantitative real time polymerase chain reaction for related osteogenic genes, and immunofluorescence staining of specific biomarkers and mineral deposits demonstrated that the ligand-free NaYF4:Yb/Er nanocrystals at a proper concentration can enhance osteogenic differentiation. Finally, intracytoplasmic lipid detection showed that the adipogenic differentiation of rBMSCs might be inhibited in the presence of ligand-free NaYF4:Yb/Er nanocrystals. Meanwhile, these results showed that the effects of ligand-free NaYF4:Yb/Er nanocrystals on rBMSCs were concentration-dependent and reciprocal between osteogenic and adipogenic differentiation. This work provides new insights into the exploring the biocompatibility of UCNPs and will benefit the research community engaged in nanotechnology and biomedicine. [ABSTRACT FROM AUTHOR]