The effects of inulin on solubilizing and improving anti-obesity activity of high polymerization persimmon tannin.

High polymerization persimmon tannin has been reported to have lipid-lowering effects. Unfortunately, the poor solubility restricts its application. This research aimed to investigate the effect and mechanism of inulin on solubilizing of persimmon tannin. Furthermore, we examined whether the addition of inulin would affect the attenuated obesity effect of persimmon tannin. Transmission electron microscope (TEM), Isothermal titration calorimetry (ITC) and Fourier transform infrared spectroscopy (FT-IR) results demonstrated that inulin formed a gel-like network structure, which enabled the encapsulation of persimmon tannin through hydrophobic and hydrogen bond interactions, thereby inhibiting the self-aggregation of persimmon tannin. The turbidity of the persimmon tannin solution decreased by 56.2 %, while the polyphenol content in the supernatant increased by 60.0 %. Furthermore, biochemical analysis and 16s rRNA gene sequencing technology demonstrated that persimmon tannin had a significant anti-obesity effect and improved intestinal health in HFD-fed mice. Moreover, inulin was found to have a positive effect on enhancing the health benefits of persimmon tannin, including improving hepatic steatosis and gut microbiota dysbiosis. it enhanced the abundance of beneficial core microbes while decreasing the abundance of harmful bacteria. Our findings expand the applications of persimmon tannin in the food and medical sectors.

Ultrasonic-assisted green extraction and incorporation of Spirulina platensis bioactive components into turmeric essential oil-in-water nanoemulsion for enhanced antioxidant and antimicrobial activities.

The utilization of essential oils as natural antioxidants and preservatives is limited by high volatility, poor water solubility, and long-term instability. To address this, a novel ultrasonic-assisted method was used to prepare and stabilize a nanoemulsion of turmeric essential oil-in-water, incorporating bioactive components extracted from Spirulina platensis. Ultrasonic treatment enhanced the extraction efficacy and nanoemulsion stability. Algal biomass subjected to ultrasonic treatment (30 min at 80% amplitude) yielded a dry extract of 73.66 ± 3.05%, with the highest protein, phenolic, phycocyanin, and allophycocyanin content, as well as maximum emulsifying activity. The resulting nanoemulsion (5% oil, 0.3% extract, 10 min ultrasonic treatment) showed reduced particle size (173.31 ± 2.24 nm), zeta potential (-36.33 ± 1.10 mV), low polydispersity index, and enhanced antioxidant and antibacterial properties. Rheology analysis indicated shear-thinning behavior, while microscopy and spectroscopy confirmed structural changes induced by ultrasonic treatment and extract concentration. This initiative developed a novel ultrasonic-assisted algal-based nanoemulsion with antioxidant and antibacterial properties.

[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

Robot-assisted minimally invasive bronchial resection with primary anastomosis for schwannoma arising from left main bronchus: a case report.

Background: Tracheobronchial schwannomas are extremely rare, which account for lower than 0.2% in all pulmonary tumors. In large part because of the rarity and insufficient reported clinical details, tracheobronchial schwannoma lacks guidelines or expert consensus for diagnosis and treatment, and the delay in diagnosis can range from months to years. The main treatment option is surgery. Endoscopic intervention can also be selected. An increasing number of thoracic surgery cases were performed on the robotic platforms in recent years. With their assistance, surgeons can accomplish the high technique required surgical procedures with ease. Case Description: In this case, a 48-year-old female had a history of shortness of breath for more than 1 year. The chest computed tomography (CT) and bronchoscopy examination revealed a new growth of nodule in the left main bronchus. The nodule was considered a schwannoma by transbronchial biopsy, which was removed by robot-assisted bronchial resection with primary anastomosis. The application of Da Vinci Si robotic surgical system benefited the process of this surgery. Pathology and immunohistochemistry results confirmed the diagnosis of schwannomas. The patient tolerated the treatment without any complications. No sign of recurrence was discovered at present, 6 months after the intervention. Conclusions: We reported the first sleeve resection for bronchial schwannoma using Da Vinci robotic surgical system. The clinical details of tracheobronchial schwannoma should be revealed more specifically to achieve more systematic diagnosis and treatment.

Differential Cantilever Enhanced Fiber-Optic Photoacoustic Sensor for Diffusion Gas Detection.

Aiming at the problem of the fiber-optic photoacoustic (PA) sensor being easily disturbed by external vibration and noise, a differential cantilever enhanced fiber-optic PA sensor is proposed for diffusion gas detection. The sensor comprises two PA tubes with the same structure and a pair of differential interferometric cantilevers. The two PA tubes are symmetrically distributed. The laser is incident on the PA tube as the signal channel to excite the PA pressure wave. Another tube without incident laser is used as the reference channel to suppress external disturbance. The external interference signals and PA signals superimposed with disturbance are detected by the differential cantilevers from the two channels. The signals are simultaneously restored by a single white-light interferometry demodulator, which multiplexed the spectral frequency domain of the superimposed interference spectrum. The experimental results show that the suppression effect of the differential cantilever enhanced PA sensor on ambient noise is improved by 80%, compared to the traditional single-cantilever sensor. The external cofrequency disturbance is suppressed by 20.9 dB. The minimum detection limit to acetylene (C2H2) downs to about 60 ppb with an integration time of 100 s. The sensor has excellent antivibration and electromagnetic interference ability.

Online tools to predict individualised survival for primary oesophageal cancer patients with and without pathological complete response after neoadjuvant therapy followed by oesophagectomy: development and external validation of two independent nomograms.

OBJECTIVE: This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy. DESIGN: Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models. RESULTS: In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system. CONCLUSIONS: The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

Immune microenvironment heterogeneity of concurrent adenocarcinoma and squamous cell carcinoma in multiple primary lung cancers.

The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and five gene sets upregulated in the ADC group. Reactome enrichment analysis of differentially expressed genes showed that the immune function-related pathways, including programmed cell death, innate immune system, interleukin-12 family signaling, and toll-like receptor 2/4 pathways, etc. were significantly enriched. Transcriptomic TIME analysis, with mIHC in patient specimens and in vivo validation, showed tumor-infiltrating immune cells were significantly more enriched and diverse in ADC, especially CD8 + T cells. Our results revealed that the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions in MPLCs.

A non-metal single atom nanozyme for cutting off the energy and reducing power of tumors.

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.

High-Precision Multipass Fiber-Optic Photoacoustic Gas Analyzer Based on 2f/1f Wavelength Modulation Spectroscopy.

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies.

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Dietary antioxidant quercetin overcomes the acquired resistance of Sorafenib in Sorafenib-resistant hepatocellular carcinoma cells through epidermal growth factor receptor signaling inactivation.

Sorafenib (SOR) is a molecular targeting agent commonly utilized as a primary treatment for advanced and inoperable hepatocellular carcinoma (HCC). Regrettably, the effectiveness of SOR is frequently hindered by the resistance of multiple HCC cases. The current investigation endeavors to examine the potential of the natural product quercetin (QUE) in reversing the acquired resistance of SOR-resistant cells, known as Huh7R, to SOR. Moreover, this study aims to elucidate the underlying molecular mechanism that contributes to this phenomenon. The results demonstrated that QUE significantly impeded proliferation and stimulated apoptosis in Huh7R cells, while also suppressing the growth of transplanted tumors. The impact of QUE enhanced the efficacy of SOR treatment for Huh7R. Additionally, bioinformatic and western blot analyses indicated that the underlying mechanisms may be associated with EGFR tyrosine kinase inhibitor resistance, the PI3K-AKT signaling pathway, and HCC. Furthermore, molecular docking and dynamics simulation assays revealed that QUE exhibited strong affinity and stability towards its hub targets, EGFR and AKT1. It is noteworthy that the activation of EGFR by its ligand, EGF, mitigated the effects of co-treatment with QUE and SOR. These findings suggest that QUE might potentially serve as a therapeutic agent in treating as well as facilitating SOR against Huh7R cells, which has substantial clinical and research implications for the treatment of acquired resistance to SOR in HCC.

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review).

RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6­methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase­like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.

BACKGROUND: Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events. METHODS: We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets. RESULTS: It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors. CONCLUSION: Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.

Structure transformation from Sierpinski triangles to chains assisted by gas molecules.

Reversible transformations between fractals and periodic structures are of fundamental importance for understanding the formation mechanism of fractals. Currently, it is still a challenge to controllably achieve such a transformation. We investigate the effect of CO and CO2 molecules on Sierpinski triangles (STs) assembled from Fe atoms and 4,4″-dicyano-1,1':3',1″-terphenyl (C3PC) molecules on Au surfaces. Using scanning tunneling microscopy, we discover that the gas molecules induce a transition from STs into 1D chains. Based on density functional theory modeling, we propose that the atomistic mechanism involves the transformation of a stable 3-fold coordination Fe(C3PC)3 motif to Fe(C3PC)4 with an axially bonded CO molecule. CO2 causes the structural transformation through a molecular catassembly process.

Comprehensively Optimizing Fenton Reaction Factors for Antitumor Chemodynamic Therapy by Charge-Reversal Theranostics.

Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(ß-amino esters) (PEG-PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG-PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG-PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.

Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit.

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

Overexpression of microRNA-93-5p and microRNA-374a-5p Suppresses the Osteogenic Differentiation and Mineralization of Human Aortic Valvular Interstitial Cells Through the BMP2/Smad1/5/RUNX2 Signaling Pathway.

ABSTRACT: Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.

Terpyridine-Grafted Nitrogen-Terminal Endowing Cyanine with Metal-Ion-Regulated Photophysical Properties for Cancer Theranostics.

Heptamethine cyanines (Cy7) are one of the most important dyes in bioimaging and phototherapy, but they often suffer from poor photostability or limited photothermal conversion efficiency. Here, a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is demonstrated. By innovatively modifying the nitrogen with functional groups, a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold (denoted as CydtPy) was synthesized and exhibited tunable photophysical properties when chelating with various metal ions (Mn2+, Fe2+, etc.). In comparison with metal-ion-free PEGylated CydtPy (LET-11), Mn2+-chelated LET-11 (namely, LET-11-Mn) exhibited the increased fluorescence emission intensity, and Fe2+-chelated LET-11 (namely, LET-11-Fe) showed the enhanced photostability with ~2-fold increase in photothermal conversion efficiency. By simply switching the chelated metal ion species, LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging, magnetic resonance imaging, or photoacoustic imaging. Furthermore, LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in vivo. This work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.