MiR-22-3p facilitates bone marrow mesenchymal stem cell osteogenesis and fracture healing through the SOSTDC1-PI3K/AKT pathway.

Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p. MiR-22-3p and sclerostin domain-containing 1 (SOSTDC1) expression was determined by RT-qPCR and immunohistochemistry staining. The levels of proteins associated with osteogenic differentiation were assessed by western blotting. Flow cytometry was conducted to identify the isolated rat BMSCs. Alizarin red staining, alkaline phosphatase staining and Oil Red O staining were used to evaluate the osteogenic and adipogenic differentiation of rat BMSCs. The interaction between miR-22-3p and SOSTDC1 was verified using a luciferase reporter assay. Haematoxylin and Eosin (H&E) staining of the bone tissues was performed to analyse the effect of miR-22-3p on histopathological changes in vivo. MiR-22-3p was downregulated in the callus tissues of rat femoral fracture, while the expression of SOSTDC1 was upregulated. The isolated rat BMSCs had the capacity for both osteogenic and adipogenic differentiation. The differentiation capacity of BMSCs into osteoblasts was increased by miR-22-3p overexpression. MiR-22-3p activated the PI3K/AKT pathway by targeting SOSTDC1. SOSTDC1 overexpression and PI3K/AKT signalling inhibitor LY294002 abolished the enhancing effect of miR-22-3p overexpression on the osteogenesis of BMSCs. Thus MiR-22-3p facilitated the femoral fracture healing in rats. MiR-22-3p overexpression promoted fracture healing via the activation of PI3K/AKT pathway by targeting SOSTDC1.

Identification of zebrafish PLEKHF2 presents in egg/embryos as an antibacterial protein.

PLEKHF2 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that PLEKHF2 is a newly identified present abundantly in the eggs/embryos of zebrafish. We also show that recombinant PLEKHF2 acts as a pattern recognition receptor capable of identifying the bacterial signature molecule PGN, LPS, and LTA, binding the bacteria, and functions as an antibacterial effector directly killing the bacteria. In brief, these results indicate that PLEKHF2 is an antibacterial protein, a novel role assigned to PLEKHF2 proteins.

Analysis of Characteristics of Patients with Non-ST-Segment Elevation Myocardial Infarction by Cardiac Magnetic Resonance Imaging.

BACKGROUND In this study, cardiac magnetic resonance imaging was used to investigate the characteristics of patients who have total coronary occlusion but manifest with non-ST-segment elevation myocardial infarction (NSTEMI), and we assessed the extent of infarct transmurality and myocardial necrosis size in NSTEMI patients. MATERIAL AND METHODS We enrolled all patients diagnosed at our hospital with subtotal or total occlusion of the culprit artery (TOCA), based on the coronary angiography, who successfully underwent PCI within 12 h of admission, and who had CMR imaging performed within 2 days after the PCI. RESULTS Based on 12-lead ECG findings, 48% of patients were categorized as having STEMI and 52% as having NSTEMI. TOCA was detected by coronary angiography in 43% of NSTEMI patients, and in 60% and 33% of normal ST segment and ST-segment depression MI patients, respectively. The transmural segments were found in 78% of STEMI patients and 31% of NSTEMI patients (P<0.05). Transmural infarction segments were found in 64% of NSTEMI patients with TOCA and in 8% of NTOCA patients (P<0.05). Moreover, the number of transmural segments in ST-segment depression MI patients was the lowest (P<0.05). Infarct size in STEMI patients was significantly larger than in patients with NSTEMI (P<0.05), whereas there was no statistically significant difference in patients with normal ST segment and ST-segment depression MI patients (P>0.05). CONCLUSIONS Identification TOCA by coronary angiography and transmural infarction by DE-MRI can be challenging in AMI patients with non-ST-segment elevation. In approximately 30% of non-ST-segment elevation MI patients, transmural infarction was detected by DE-MRI. Therefore, TOCA accompanied by transmural infarction in non-ST-segment-elevation MI patients is not uncommon.

Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping.

Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR inhibitors has successfully yielded a novel series of highly potent FGFR4 inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic ring count, this series demonstrated improved solubility and permeability. However, plasma instability and fast metabolism limited its potential for in vivo studies. Efforts have been made to address these problems, which led to the discovery of compound (-)-11 with improved stability, CYP inhibition, and good activity/selectivity for further optimization.

Optimization of Profile Control and Oil Displacement Scheme Parameters Based on Deep Deterministic Policy Gradient.

The parameter design of profile control and oil displacement (PCOD) scheme plays an important role in improving waterflooding efficiency and increasing the oil field production and recovery. In this paper, the parameter optimization model and solution method of the PCOD scheme based on deep deterministic policy gradient (DDPG) are constructed with the half-year increased oil production (Qi) of injection well group as the objective function and the parameter range of PCOD system type, concentration, injection volume, and injection rate as constraints. Using the historical data of PCOD and extreme gradient boosting (XGBoost) method to construct a proxy model of PCOD process as the environment, the change rate of Qi of well groups before and after optimization is taken as the reward function; the system type, concentration, injection volume, and injection rate are taken as the action; and the Gaussian strategy with noise is taken as the action exploration strategy. Taking XX block of offshore oil field as an example, the parameters of the compound slug PCOD process (pre-slug + main slug + protection slug) of the injection well group are analyzed, that is, parameters such as the system type, concentration, injection volume, and injection rate of each slug system are optimized. The research shows that the parameter optimization model of the PCOD scheme established based on DDPG can obtain higher oil production PCOD scheme for well groups with different PCOD, and has strong optimization and generalization ability compared with the particle swarm optimization (PSO) model.

Association of GSDMD with microvascular-ischemia reperfusion injury after ST-elevation myocardial infarction.

Objectives: Little is known about the clinical prognosis of gasdermin D (GSDMD) in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate the association of GSDMD with microvascular injury, infarction size (IS), left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACEs), in STEMI patients with primary percutaneous coronary intervention (pPCI). Methods: We retrospectively analyzed 120 prospectively enrolled STEMI patients (median age 53 years, 80% men) treated with pPCI between 2020 and 2021 who underwent serum GSDMD assessment and cardiac magnetic resonance (CMR) within 48 h post-reperfusion; CMR was also performed at one year follow-up. Results: Microvascular obstruction was observed in 37 patients (31%). GSDMD concentrations ≧ median (13 ng/L) in patients were associated with a higher risk of microvascular obstruction and IMH (46% vs. 19%, P = 0.003; 31% vs. 13%, P = 0.02, respectively), as well as with a lower LVEF both in the acute phase after infarction (35% vs. 54%, P < 0.001) and in the chronic phase (42% vs. 56%, P < 0.001), larger IS in the acute (32% vs. 15%, P < 0.001) and in the chronic phases (26% vs. 11%, P < 0.001), and larger left ventricular volumes (119 ± 20 vs. 98 ± 14, P = 0.003) by CMR. Univariable and multivariable Cox regression analysis results showed that patients with GSDMD concentrations ≧ median (13 ng/L) had a higher incidence of MACE (P < 0.05). Conclusions: High GSDMD concentrations in STEMI patients are associated with microvascular injury (including MVO and IMH), which is a powerful MACE predictor. Nevertheless, the therapeutic implications of this relation need further research.

Immune cells regulate matrix metalloproteinases to reshape the tumor microenvironment to affect the invasion, migration, and metastasis of pancreatic cancer.

This study aimed to identify author, country, institutional, and journal collaborations and assess their impact, along with knowledge base, as well as identify existing trends, and uncover emerging topics related to matrix metalloproteinase and pancreatic-cancer research. A total of 1474 Articles and reviews were obtained from the Web of Science Core Collection and analyzed by Citespace and Vosviewer. CANCER RESEARCH, CLINICAL CANCER RESEARCH, and FRONTIERS IN IMMUNOLOGY are the most influential journals. The three main aspects of research in matrix metalloproteinases-pancreatic cancer-related fields included the pathogenesis mechanism of pancreatic cancer, how matrix metalloproteinases affect the metastasis of pancreatic cancer, and what role matrix metalloproteinases play in pancreatic cancer treatment. Tumor microenvironment, pancreatic stellate cells, drug resistance, and immune cells have recently emerged as research hot spots. In the future, exploring how immune cells affect matrix metalloproteinases and reshape the tumor microenvironment may be the key to curing pancreatic cancer. This study thus offers a comprehensive overview of the matrix metalloproteinases-pancreatic cancer-related field using bibliometrics and visual methods, providing a valuable reference for researchers interested in matrix metalloproteinases-pancreatic cancer.

Therapeutic effects of adriamycin combined with high-intensity focused ultrasound on osteosarcoma.

PURPOSE: To analyze the efficacy of adriamycin (ADM) combined with high-intensity focused ultrasound (HIFU) in patients with osteosarcoma. METHODS: A total of 72 patients with osteosarcoma were selected and divided into the control group (n=36) and the observation group (n=36). Patients in the control group were treated with ADM, while those in the observation group received HIFU in addition to ADM. The efficacy and adverse reactions in the observation and control group were compared. RESULTS: The response rate and disease control rate in the observation group were significantly higher than those in the control group (p<0.05). No significant difference was found in the survival rate at year 1 after treatment between the two groups, but the observation group had overtly higher survival rates at years 2 and 3 after treatment in comparison with the control group (p<0.05). There was no obvious difference in the incidence rate of adverse reactions between the observation and control group. After treatment, the levels of serum tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2) and IL-8 in the observation group were clearly higher than those in the control group. Serum alkaline phosphatase (ALP) and creatinine (Cr) in the observation and control group showed no significant differences. Compared with the control group, ALP level was significantly decreased in the observation group (p<0.05). The limb function and psychological behavior after treatment in the observation group were significantly superior to those in the control group (p<0.05). CONCLUSIONS: The application of ADM combined with HIFU is conducive to improving efficacy on osteosarcoma, prolonging survival and improving prognosis.

SDF-1/CXCR4 promotes F5M2 osteosarcoma cell migration by activating the Wnt/ß-catenin signaling pathway.

Osteosarcoma (OS), the most common primary malignant bone tumor in children and adolescents, lacks an effective therapy. Stromal cell-derived factor (SDF-1) and its receptor, CXCR4, play multiple roles in migration, proliferation, and survival of different tumor cells. This study aimed to investigate whether the functional SDF-1/CXCR4 signaling mediates chemotaxis in F5M2 OS cells as well as the underlying mechanisms. Immunohistochemistry and immunofluorescence microscopy were used. RNA expression was detected by real-time quantitative polymerase chain reaction, and protein expression was examined by Western blotting. Migration assays were carried out in F5M2 cells. The results showed that the expression of CXCR4 and ß-catenin mRNA and protein was significantly higher in OS tissues compared to the surrounding non-neoplastic tissues. SDF-1 promoted F5M2 cell migration by activating the AKT and Wnt/ß-catenin signaling pathway, which was abrogated by preincubation with AMD3100 and LY294002. In conclusion, SDF-1/CXCR4 axis-promoted F5M2 cell migration was regulated by the Wnt/ß-catenin signaling pathway.

Resource optimized TTSH-URA for multimedia stream authentication in swallowable-capsule-based wireless body sensor networks.

To ease the burdens on the hospitalization capacity, an emerging swallowable-capsule technology has evolved to serve as a remote gastrointestinal (GI) disease examination technique with the aid of the wireless body sensor network (WBSN). Secure multimedia transmission in such a swallowable-capsule-based WBSN faces critical challenges including energy efficiency and content quality guarantee. In this paper, we propose a joint resource allocation and stream authentication scheme to maintain the best possible video quality while ensuring security and energy efficiency in GI-WBSNs. The contribution of this research is twofold. First, we establish a unique signature-hash (S-H) diversity approach in the authentication domain to optimize video authentication robustness and the authentication bit rate overhead over a wireless channel. Based on the full exploration of S-H authentication diversity, we propose a new two-tier signature-hash (TTSH) stream authentication scheme to improve the video quality by reducing authentication dependence overhead while protecting its integrity. Second, we propose to combine this authentication scheme with a unique S-H oriented unequal resource allocation (URA) scheme to improve the energy-distortion-authentication performance of wireless video delivery in GI-WBSN. Our analysis and simulation results demonstrate that the proposed TTSH with URA scheme achieves considerable gain in both authenticated video quality and energy efficiency.

Sensitive determination of endogenous hexanal and heptanal in urine by hollow-fiber liquid-phase microextraction prior to capillary electrophoresis with amperometric detection.

Hexanal (Hex) and heptanal (Hep) in human blood have been regarded as potential biomarkers of lung cancer. In this work, a hollow-fiber liquid-phase microextraction (HF-LPME) method has been developed for the preconcentration of these trace aldehydes in urine samples. After derivatization with an electroactive compound 2-thiobarbituric acid, these two non-electroactive aldehydes were converted to electroactive adducts, therefore detectable by capillary zone electrophoresis with amperometric detection (CZE-AD) approach. Experimental conditions of derivatization, extraction, electrophoretic separation and detection were optimized. Under the optimum conditions, the enrichment factors for Hex and Hep could reach 320 and 355, respectively. The limits of detection for Hex and Hep were 2.7 and 0.97 nM, respectively; the average recoveries were in the range of 61-95% and relative standard deviation (RSD) values less than 8.5%. The present method has been applied to quantitative analysis of two biomarkers in human urine in lieu of blood samples, and the assay results showed that the contents of Hex (0.99-6.7 µM) and Hep (2.5-6.4 µM) found in the urine sample of the lung cancer patients were significantly higher than those in the healthy volunteers, liver cancer patients, as well as diabetics. The proposed HF-LPME/CZE-AD method may provide a potential alternative for early non-invasive diagnosis of lung cancer disease.