Risk Factors of Serious Adverse Events for Geriatric Hip Fractures: Is it the Frailty or the Timing?

Objective: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization. Methods: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes. Results: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities (P < .001), lower surgical rates (P = .002), and delayed surgical times (P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications. Conclusions: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer.

BACKGROUND: Ferroptosis has recently been associated with multiple degenerative diseases. Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases. However, the association of iron proliferation-related genes with prognosis in HER2+ breast cancer (BC) patients is unclear. AIM: To identify and evaluate fresh ferroptosis-related biomarkers for HER2+ BC. METHODS: First, we obtained the mRNA expression profiles and clinical information of HER2+ BC patients from the TCGA and METABRIC public databases. A four-gene prediction model comprising PROM2, SLC7A11, FANCD2, and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort. Patients were stratified into high-risk and low-risk groups based on their median risk score, an independent predictor of overall survival (OS). Based on these findings, immune infiltration, mutations, and medication sensitivity were analyzed in various risk groupings. Additionally, we assessed patient prognosis by combining the tumor mutation burden (TMB) with risk score. Finally, we evaluated the expression of critical genes by analyzing single-cell RNA sequencing (scRNA-seq) data from malignant vs normal epithelial cells. RESULTS: We found that the higher the risk score was, the worse the prognosis was (P < 0.05). We also found that the immune cell infiltration, mutation, and drug sensitivity were different between the different risk groups. The high-risk subgroup was associated with lower immune scores and high TMB. Moreover, we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses. HRisk-HTMB patients had the worst prognosis, whereas LRisk-LTMB patients had the best prognosis (P < 0.0001). Analysis of the scRNA-seq data showed that PROM2, SLC7A11, and FANCD2 were significantly differentially expressed, whereas FH was not, suggesting that these genes are expressed mainly in cancer epithelial cells (P < 0.01). CONCLUSION: Our model helps guide the prognosis of HER2+ breast cancer patients, and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Detection of uridine diphosphate glucuronosyltransferase 1A1 for pancreatic cancer imaging and treatment via a "turn-on" fluorescent probe.

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is expressed ubiquitously in cancer cells and can metabolize exogenous substances. Studies show higher UGT1A1 levels in pancreatic cancer cells than normal cells. Therefore, we need a method to monitor the activity level of UGT1A1 in pancreatic cancer cells and in vivo. Here, we report a fluorescent probe, BCy-panc, for UGT1A1 imaging in cells and in vivo. Compared with other molecular probes, this probe is readily prepared, with high selectivity and sensitivity for the detection of UGT1A1. Our results show that BCy-panc rapidly detects UGT1A1 in pancreatic cancer. In addition, there is an urgent need for evidence to clarify the relationship between UGT1A1 and pancreatic cancer development. The present investigation found that the increase of UGT1A1 by chrysin was effective in inducing apoptosis in pancreatic cancer cells. These results indicate that the synergistic effect of chrysin and cisplatin at the cellular level is superior to that of cisplatin alone. The UGT1A1 level may be a biomarker for early diagnosis of cancer. Meanwhile, UGT1A1 plays a crucial role in pancreatic cancer, and the combination of chrysin and cisplatin may provide effective ideas for pancreatic cancer treatment.

CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain.

Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Mature compost promotes biodegradable plastic degradation and reduces greenhouse gas emission during food waste composting.

Mature compost can promote the transformation of organic matter (OM) and reduce the emission of polluting gases during composting, which provides a viable approach to reduce the environmental impacts of biodegradable plastics (BPs). This study investigated the impact of mature compost on polybutylene adipate terephthalate (PBAT) degradation, greenhouse gas (GHG) emission, and microbial community structure during composting under two treatments with mature compost (MC) and without (CK). Under MC, visible plastic rupture was advanced from day 14 to day 10, and a more pronounced rupture was observed at the end of composting. Compared with CK, the degradation rate of PBAT in MC was increased by 4.44 % during 21 days of composting. Thermobifida, Ureibacillus, and Bacillus, as indicator species under MC treatment, played an important role in PBAT decomposition. Mature compost reduced the total global warming potential (GWP) by 25.91 % via inhibiting the activity of bacteria related to the production of CH4 and N2O. Functional Annotation of Prokaryotic Taxa (FAPROTAX) further revealed that mature compost addition increased relative abundance of bacteria related to multiple carbon (C) cycle functions such as methylotrophy, hydrocarbon degradation and cellulolysis, inhibited nitrite denitrification and denitrification, thus alleviating the emission of GHGs. Overall, mature compost, as an effective additive, exhibits great potential to simultaneously mitigate BP and GHG secondary pollution in co-composting of food waste and PBAT.

Recent advances in functional micro/nanomaterials for removal of crude oil via thermal effects.

Crude oil is one of the most widely used energy and industrial raw materials that is crucial to the world economy, and is used to produce various petroleum products. However, crude oil often spills during extraction, transportation and use, causing negative impacts on the environment. Thus, there is a high demand for products to remediate leaked crude oil. Among them, oleophilic and hydrophobic adsorbents can absorb crude oil through thermal effects and are research hotspots. In this review, we first present an overview of wettability theory, the heating principles of various thermal effects, and the theory of reducing crude oil viscosity by heating. Then we discuss adsorbents based on different heating methods including the photothermal effect, Joule heating effect, alternating magnetic field heating effect, and composite heating effect. Preparation methods and oil adsorption performance of adsorbents are summarized. Finally, the advantages and disadvantages of various heating methods are briefly summarized, as well as the prospects for future research.

Using machine learning to predict selenium and cadmium contents in rice grains from black shale-distributed farmland area.

Cadmium (Cd) and selenium (Se) are widely enriched in soil at black shale outcropping areas, with Cd levels exceeding the standard (2.0 mg/kg in 5.5 < pH ≤ 6.5) commonly. The prevention of Cd hazards and the safe development of Se-rich land resources are key issues that need to be urgently addressed. To ensure safe utilization of Se-rich land in the CdSe coexisting areas, 158 rice samples, their corresponding rhizosphere soils, and 8069 topsoil samples were collected and tested in the paddy fields of Ankang City, Shaanxi Province, where black shales are widely exposed. The results showed that 43 % of the topsoil samples were Se-rich soil (Se > 0.4 mg/kg) wherein 79 % and 3 % of Cd concentrations exceeded the screening value and control value, respectively, according to the GB15618-2018 standard. Meanwhile, 63 % of the rice samples were Se rich (Se > 0.04 mg/kg) and the Cd content exceeded the prescribed limit (0.2 mg/kg) in Se-rich rice by 26 %. There was no significant positive correlation between the Se and Cd contents in the rice grains and the Se and Cd contents in the corresponding rhizosphere soil. The factors influencing Se and Cd uptake in rice were SiO2, CaO, P, S, pH, and TFe2O3. Accordingly, an artificial neural network (ANN) and multiple linear regression model (MLR) were used to predict Cd and Se bioaccumulation in rice grains. The stability and accuracy of the ANN model were better than those of the MLR model. Based on survey data and the prediction results of the ANN model, a safe planting zoning of Se-rich rice was proposed, which provided a reference for the scientific planning of land resources.

TREM2 mediates MHCII-associated CD4+ T cell response against gliomas.

BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors. METHODS: We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both glioblastoma patients and the GL261 mouse glioma model. We utilized multiple mouse glioma models and employed state-of-the-art techniques such as in vivo two-photon imaging, spectrum flow cytometry, and in vitro co-culture assays to study TREM2 function in myeloid cell-mediated phagocytosis of tumor cells, antigen presentation, and response of CD4+ T cells within the tumor hemispheres. RESULTS: Our research revealed significantly elevated levels of TREM2 expression in brain tumors compared to other types of tumors in patients. TREM2 was predominantly localized in tumor-associated myeloid cells and was highly expressed in nearly all microglia, as well as various subtypes of macrophages. Surprisingly, in pre-clinical glioma models, TREM2 deficiency did not confer a beneficial effect; instead, it accelerated glioma progression. Through detailed investigations, we determined that TREM2 deficiency impaired the ability of tumor-myeloid cells to phagocytose tumor cells and led to reduced expression of MHCII. This deficiency further significantly decreased the presence of CD4+ T cells within the tumor hemispheres. CONCLUSIONS: Our study unveiled a previously unrecognized protective role of tumor-myeloid TREM2. Specifically, we found TREM2 enhance the phagocytosis of tumor cells and promote an immune response by facilitating MHCII-associated CD4+ T cell responses against gliomas.

Lightweight deep learning model incorporating an attention mechanism and feature fusion for automatic classification of gastric lesions in gastroscopic images.

Accurate diagnosis of various lesions in the formation stage of gastric cancer is an important problem for doctors. Automatic diagnosis tools based on deep learning can help doctors improve the accuracy of gastric lesion diagnosis. Most of the existing deep learning-based methods have been used to detect a limited number of lesions in the formation stage of gastric cancer, and the classification accuracy needs to be improved. To this end, this study proposed an attention mechanism feature fusion deep learning model with only 14 million (M) parameters. Based on that model, the automatic classification of a wide range of lesions covering the stage of gastric cancer formation was investigated, including non-neoplasm(including gastritis and intestinal metaplasia), low-grade intraepithelial neoplasia, and early gastric cancer (including high-grade intraepithelial neoplasia and early gastric cancer). 4455 magnification endoscopy with narrow-band imaging(ME-NBI) images from 1188 patients were collected to train and test the proposed method. The results of the test dataset showed that compared with the advanced gastric lesions classification method with the best performance (overall accuracy = 94.3%, parameters = 23.9 M), the proposed method achieved both higher overall accuracy and a relatively lightweight model (overall accuracy =95.6%, parameter = 14 M). The accuracy, sensitivity, and specificity of low-grade intraepithelial neoplasia were 94.5%, 93.0%, and 96.5%, respectively, achieving state-of-the-art classification performance. In conclusion, our method has demonstrated its potential in diagnosing various lesions at the stage of gastric cancer formation.

Modification of Low-Energy Surfaces Using Bicyclic Peptides Discovered by Phage Display.

Solid-binding peptides are a simple and versatile tool for the non-covalent modification of solid material surfaces, and a variety of peptides have been developed by reference to natural proteins or de novo design. Here, for the first time, we report the discovery of a bicyclic peptide targeting the heterogeneous material polypropylene by combining phage display technology and next-generation sequencing. We find that the enrichment properties of bicyclic peptides capable of binding to polypropylene are distinct from linear peptides, as reflected in amino acid abundance and a trend toward negative net charges and high hydrophobicity. The selected bicyclic peptide has a higher binding affinity for polypropylene compared with a previously reported linear peptide, enabling the hydrophilic and adhesive properties of the polypropylene to be more effectively enhanced. Our work paves the way for the exploration and utilization of conformational-restricted cyclic peptides as a new family of functionally evolvable agents for material surface modification.

Chemogenetic manipulation of CX3CR1+ cells transiently induces hypolocomotion independent of microglia.

Chemogenetic approaches using Designer Receptors Exclusively Activated by Designer Drugs (DREADD, a family of engineered GPCRs) were recently employed in microglia. Here, we used Cx3cr1CreER/+:R26hM4Di/+ mice to express Gi-DREADD (hM4Di) on CX3CR1+ cells, comprising microglia and some peripheral immune cells, and found that activation of hM4Di on long-lived CX3CR1+ cells induced hypolocomotion. Unexpectedly, Gi-DREADD-induced hypolocomotion was preserved when microglia were depleted. Consistently, specific activation of microglial hM4Di cannot induce hypolocomotion in Tmem119CreER/+:R26hM4Di/+ mice. Flow cytometric and histological analysis showed hM4Di expression in peripheral immune cells, which may be responsible for the hypolocomotion. Nevertheless, depletion of splenic macrophages, hepatic macrophages, or CD4+ T cells did not affect Gi-DREADD-induced hypolocomotion. Our study demonstrates that rigorous data analysis and interpretation are needed when using Cx3cr1CreER/+ mouse line to manipulate microglia.

Analysis of clinical characteristics and prognostic factors of elderly patients with renal cell carcinoma based on the SEER database.

To study the difference of clinical characteristics and prognostic factors from elderly patients with renal cell carcinoma (RCC), the statistical analysis was carried out based on the surveillance, epidemiology, and end results database. The relevant clinical information of 19,472 RCC patients from 2010 to 2015 were collected, and the differences of clinicopathological characteristics and survival rate was analyzed by log-rank method and Chi square test, respectively. Multivariate Cox regression model was used to explore the independent risk factors affecting the long-term survival of RCC patients. Results showed that the proportion of elderly RCC patients in the 60-64-year group in 2010 was 15.20%, but the value elevated to 18.51% in 2015, and the Chi-square test revealed the significant correlation between elderly RCC patients with gender, race, American Joint Committee on cancer stage, T stage, N stage, and M stage. The difference of survival time between the 60-69 year, 70-79 year, 80-84 year, and 85+ year group was significant, and Kaplan-Meier analysis showed a negative effects of age on survival rate of RCC patients, indicating a worsening trend with increasing age. Cox proportional hazards model analysis further confirmed that age was the important independent prognostic factor. Our study reveals that the onset age of RCC in elderly population is gradually decreasing, and the malignant degree of elderly RCC patients is increasing with age. The female elderly population could be more susceptible to RCC than male elderly population, and 85+ year population could also be cancer susceptible with a higher lymph node metastasis rate, later tumor stage, and poor prognosis, suggesting that these elderly populations should pay more attention to the RCC screening.

TREM2 mediates MHCII-associated CD4+ T cell response against gliomas.

Triggering receptor expressed on myeloid cells 2 (TREM2) was recently highlighted as a novel immune suppressive marker in peripheral tumors. The aim of this study was to characterize TREM2 expression in gliomas and investigate its contribution in glioma progression by using Trem2-/- mouse line. Our results showed that higher TREM2 expression was correlated with poor prognosis in glioma patients. Unexpectedly, TREM2 deficiency did not have a beneficial effect in a pre-clinical model of glioma. The increased TREM2 expression in glioma was likely due to increased myeloid cell infiltration, as evidenced by our single-cell analysis showing that almost all microglia and macrophages in gliomas were TREM2+. Furthermore, we found that deficiency of TREM2 impaired tumor-myeloid phagocytosis and MHCII presentation, and significantly reduced CD4+ T cells in tumor hemispheres. Our results revealed a previously unrecognized protective role of tumor-myeloid TREM2 in promoting MHCII-associated CD4+ T cell response against gliomas.

Development and validation of cuproptosis-related lncRNA signatures for prognosis prediction in colorectal cancer.

BACKGROUND: Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC. METHODS: First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan-Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model. RESULT: Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan-Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR. CONCLUSION: The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.

Evaluating the Effect of Hydrogen Sulfide in the Idiopathic Pulmonary Fibrosis Model with a Fluorescent Probe.

Hydrogen sulfide (H2S), a gaseous signaling molecule, is involved in a wide range of physiological and pathological processes. H2S has been proven to play a beneficial role in lung diseases, and the relationship between perturbations in endogenous H2S synthesis and degree with idiopathic pulmonary fibrosis (IPF) has attacted increasing attention. However, the changes in endogenous lung H2S levels in the pathological progression of chronic pulmonary diseases remain unclear. To this end, we synthesized a fluorescent probe (Bcy-HS) for the selective imaging of H2S in living cells and mice. This probe was mainly used for in situ in vivo and cellular imaging as well as a systematic assessment of intrapulmonary H2S levels at different stages of IPF. In addition, we also discussed the potential of H2S supplementation in the treatment of pulmonary fibrotic diseases. Our results confirmed the key role of H2S in pulmonary fibrosis. In cellular and mice models of pulmonary fibrosis, intracellular H2S levels are reduced. However, the severity of oxidative damage and pulmonary fibrosis decreased after NaSH (H2S donor). Therefore, we concluded that increasing the H2S content in vivo may be a novel strategy for IPF treatment.

Construction and validation of a prognostic signature based on necroptosis-related genes in hepatocellular carcinoma.

BACKGROUND: Necroptosis is a necrotic programmed cell death with potent immunogenicity. Due to the dual effects of necroptosis on tumor growth, metastasis and immunosuppression, we evaluated the prognostic value of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC). METHODS: We first analyzed RNA sequencing and clinical HCC patient data obtained to develop an NRG prognostic signature based on the TCGA dataset. Differentially expressed NRGs were further evaluated by GO and KEGG pathway analyses. Next, we conducted univariate and multivariate Cox regression analyses to build a prognostic model. We also used the dataset obtained from the International Cancer Genome Consortium (ICGC) database to verify the signature. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to investigate the immunotherapy response. Furthermore, we investigated the relationship between the prediction signature and chemotherapy treatment response in HCC. RESULTS: We first identified 36 differentially expressed genes out of 159 NRGs in hepatocellular carcinoma. Enrichment analysis showed that they were mainly enriched in the necroptosis pathway. Four NRGs were screened by Cox regression analysis to establish a prognostic model. The survival analysis revealed that the overall survival of patients with high-risk scores was significantly shorter than that of patients with low-risk scores. The nomogram demonstrated satisfactory discrimination and calibration. The calibration curves validated a fine concordance between the nomogram prediction and actual observation. The efficacy of the necroptosis-related signature was also validated by an independent dataset and immunohistochemistry experiments. TIDE analysis revealed that patients in the high-risk group were possibly more susceptible to immunotherapy. Furthermore, high-risk patients were found to be more sensitive to conventional chemotherapeutic medicines such as bleomycin, bortezomib, and imatinib. CONCLUSION: We identified 4 necroptosis-related genes and established a prognostic risk model that could potentially predict prognosis and response to chemotherapy and immunotherapy in HCC patients in the future.

High porosity 3D printed titanium mesh allows better bone regeneration.

BACKGROUND: Most patients with insufficient bone mass suffer from severe horizontal or vertical bone defects in oral implant surgery. The purpose of this study was to compare the bone regeneration effects of titanium meshes with different porosity in the treatment of bone defects. METHODS: Nine beagle dogs were equally divided into three groups based on execution time. Three months after the extraction of the first to fourth premolars of the mandible, three bone defects were randomly made in the mandible. Bone particles and three kinds of three-dimensional (3D) printed titanium nets with different porosities (low porosity group (LP), 55%; medium porosity group (MP), 62%; and high porosity group (HP), 68%) were replanted in situ. The beagles were killed 4, 8, and 12 weeks after surgery. Formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with micro-CT, basic fuchsin staining, and toluidine blue staining. RESULTS: Micro-CT analysis showed that the trabecular thickness, trabecular number, and bone volume fraction of the HP group were higher than those of the other two groups. Moreover, the trabecular separation of the HP group decreased slightly and was lower than that of the MP and LP groups. Histological staining analysis showed that the trabecular number in the HP group was higher than in the other two groups at 8 and 12 weeks, and the bone volume fraction of the HP was higher than that in the other two groups at 12 weeks. Moreover, the trabecular thickness of the MP was higher than that of the LP group at 12 weeks and the trabecular separation was lower in the HP group at 4 and 8 weeks. The differences were statistically significant (p < 0.05). CONCLUSION: A 3D printed titanium mesh with HP in a certain range may have more advantages than a titanium mesh with LP in repairing large bone defects.

microRNA-491-5p regulates osteogenic differentiation of bone marrow stem cells in type 2 diabetes.

OBJECTIVES: Osseointegration of oral implants has a low success rate in patients with type 2 diabetes. This is because of the inhibition of osteogenic differentiation in the jawbone marrow mesenchymal stem cells, in which the expression of microRNA(miR)-491-5p is significantly downregulated, as ascertained through gene chip screening. However, the underlying mechanisms are unclear. Here, we aimed to clarify the mechanisms involved in the influence of miR-491-5p on osteogenic differentiation. SUBJECTS AND METHODS: Jawbone marrow mesenchymal stem cells were isolated from jawbones of patients with type 2 diabetes and subjected to bioinformatics and functional analyses. Osteogenesis experiments were conducted using the isolated cells and an in vivo model. RESULTS: Knockdown and overexpression experiments revealed the positive effects of miR-491-5p expression on osteogenic differentiation in vivo and in vitro. Additionally, a dual-luciferase assay revealed that miR-491-5p targeted the SMAD/RUNX2 pathway by inhibiting the expression of epidermal growth factor receptor. CONCLUSIONS: miR-491-5p is vital in osteogenic differentiation of jawbone mesenchymal stem cells; its downregulation in type 2 diabetes could be a major cause of decreased osteogenic differentiation. Regulation of miR-491-5p expression could improve osteogenic differentiation of jawbone mesenchymal stem cells in patients with type 2 diabetes.

A Raman/fluorescence dual-modal imaging guided synergistic photothermal and photodynamic therapy nanoplatform for precision cancer theranostics.

Nanoparticle-based phototherapies, such as photodynamic therapy (PDT) and photothermal therapy (PTT) are effective methods for tumor theranostics. However, there are still some problems such as lack of specificity to the special internal environment and difficulty in tumor localization. In this study, we design a near-infrared (NIR) fluorescent guided tumor therapy nanoplatform Cy-C-S-NPs for tumor therapy and precise localization. First, we synthesized a near-infrared fluorescent dye Cy-DM, combined with excellent optical and PDT/PTT properties. Interestingly, it binds Cy7 to the azo bond and mercaptoacetic acid and in the meanwhile the azo bond can be broken specifically under the condition of tumor hypoxia. Then the Au-S bond is covalently coupled with C-S-NPs, a gold nanomaterial similar to waxberry with surface-enhanced Raman function, to form the Cy-C-S-NP nanomaterial and achieve Raman imaging. In a non-anoxic environment, Cy-DM fluorescence is quenched by C-S-NPs. The unique hypoxic microenvironment of tumor cells leads to the breaking of azo bonds, releasing Cy-DM and producing fluorescence. Accurate tumor localization based on near infrared imaging diagnosis and dependent on the release of Cy-DM and C-S-NPs, PDT/PTT therapy can be performed effectively. This study provides an interesting nanoplatform that combines the functions of PDT/PTT with dual imaging effects of fluorescence and Raman imaging. This multifunctional nanoplatform may be a promising nanoplatform for targeted tumor imaging and precision therapy.