Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed ß-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/ß-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/ß-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed ß-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

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Oil and its pollutants, which enter environment through natural oil seepage and many human activities, have considerable impacts on birds. We summarized the research advances in how oil pollutants influence birds and the cleaning technology of polluted birds and their habitats. The toxicity and destruction to feather structure are the major impacts of oil pollution on birds. Oil pollution can lead to birds' death, and also produce many chronic harms, including causing hemolytic anemia, reducing their immunity, disrupting thermal insulation and waterproo-fing performance of feather. It is an important way to reduce the impacts of oil pollution on birds by timely cleaning up the oil in bird habitats as well as carrying out the clean and repair work to the polluted birds. As a big oil-consuming country, China has been left behind by foreign countries in the studies of the effects of oil pollution on birds. More attention should be paid on the short-term and long-term impacts of oil pollution on birds and the cleaning and remediation technologies of the polluted birds and their habitats.

A Comparative Analysis of Femoral Neck System and Three Cannulated Screws Fixation in the Treatment of Femoral Neck Fractures: A Six-Month Follow-Up.

OBJECTIVE: To investigate the efficacies of Femoral Neck System (FNS) and the three cannulated screws fixation (3CS) as therapeutic options for femoral neck fractures. METHOD: This was a retrospective study involving 69 patients (26 males and 43 females; mean age of 54.9 years (range, 28-66 years)) subjected to either FNS or 3CS for femoral neck fracture therapy. These patients were treated in our hospital from October 2019 to May 2020. Patient follow up was done at 1, 2, 3 and 6 months. During the short-term (6 months) follow-up period, surgical procedures for the two groups and incidences of complications were analyzed. Perioperative parameters were recorded and analyzed. Postoperative hip joint functions were measured and compared using the Harris score. The assessed perioperative parameters included surgical time, hemoglobin loss, fluoroscopy duration, hospitalization length and hospitalization cost. The main complications at last follow-up (6 months) included varus tilting, femoral neck shortness, and implant removal. RESULTS: Differences in the number of patients, age, Garden type of fracture and time from injury to surgery between the two groups were not significant (P > 0.05). With regards to perioperative parameters, compared to 3CS, FNS treatment performed better in surgical time (60.00 ± 12.44 vs 76.81 ± 13.10 min, P = 0.000), blood loss (13.67 ± 8.02 vs 16.58 ± 4.16 g/L, P = 0.059) and fluoroscopy time (39.73 ± 9.57 vs 58.14 ± 9.15 s, P = 0.000). Differences in hospitalization length and cost between the groups were not significant (P > 0.05). During the whole follow-up period, all patients did not exhibit dysfunction, pulmonary embolism or even death as a result of long-term immobilization of affected limbs. Surgical incisions for all patients healed well without infections. During the 6-month follow-up period, the FNS group exhibited a higher Harris score (84.61 ± 3.42 vs 78.67 ± 3.72, p = 0.000). In addition, treatment-associated complications (FNS vs 3CS) included femoral neck varus tilt (3.03% vs 11.11%), femoral neck shortness (6.06% vs 13.89%), and implant removal (0% vs. 13.89%). Implant removal rate for the FNS group was significantly less than that of the 3CS group (P = 0.026). Differences in incidences of femoral neck varus tilt (P = 0.196) and femoral neck shortness (P = 0.282) between the two groups were not significant. However, the difference in number was significant (FNS group was less). CONCLUSION: FNS treatment is associated with a smaller surgical trauma, stronger stability, and reductions in post-operative complication incidences, therefore, it is a potential therapeutic option for femoral neck fractures.

Efficacy-shaping nanomedicine by loading Calcium Peroxide into Tumor Microenvironment-responsive Nanoparticles for the Antitumor Therapy of Prostate Cancer.

Rationale: Prostate cancer has become one of the most threatening malignant tumors in men, leading to an imperative need to develop effective and safe therapies. Because of the unique metabolism of tumor cells, the tumor microenvironment (TME) exhibits distinctive properties compared with normal tissues, among which the pH difference has been utilized as an ideal antitumor strategy. Herein, we introduce a reactive oxygen species (ROS)-controlled-release nanosystem with TME-responsiveness by applying hollow mesoporous silica nanoparticles (HMSNs) as carriers loaded with calcium peroxide (CaO2) and coated with polyacrylic acid (PAA) to construct the functional material CaO2@HMSNs-PAA. The differences in pH values and exogenous ROS scavenging abilities between the tumor tissue and normal tissues and the dual pH-responsiveness from CaO2 and PAA lay a scientific foundation for the application of CaO2@HMSNs-PAA in the tumor-selective therapy for prostate cancer. Methods: The morphology and the structure of the nanosystem were characterized by the transmission electron microscope, scanning electron microscope, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, zeta potential, dynamic light scattering measurement, low-angle X-ray diffraction patterns and nitrogen adsorption/desorption isotherm. The CaO2 loading capacity and release profiles in different buffer solutions were determined by inductively coupled plasma-mass spectrometry. The in vitro intracellular uptake of CaO2@HMSNs-PAA was explored on the PC-3 prostate cancer cell line via confocal laser scanning microscopy. The CCK-8 cell proliferation assay was conducted to evaluate the cytotoxicity of CaO2@HMSNs-PAA against PC-3 cells. ROS produced by CaO2@HMSNs-PAA was observed by a fluorescence microscope. The flow cytometry was utilized to analyze the apoptosis of PC-3 cells induced by CaO2@HMSNs-PAA. The Western blot analysis was performed to detect expressions of critical mitochondria-mediated apoptosis markers in PC-3 cells after incubation with CaO2@HMSNs-PAA. The in vivo biosafety and antitumor efficacy were evaluated out on BALB/c mice and BALB/c nude mice subcutaneously transplanted with PC-3 cells, respectively. Results: Comprehensive characterizations indicated the successful synthesis of CaO2@HMSNs-PAA with significant TME-responsiveness. The experimental results demonstrated that the well-developed nanocarrier could efficiently deliver CaO2 to the tumor site and release ROS in response to the decreased pH value of TME, exerting ideal antitumor effects both in vitro and in vivo by activating the mitochondria-mediated apoptosis pathway. Simultaneously, this nanoplatform caused no detectable damage to normal tissues. Conclusions: After loading into the above nanocomposite, the free CaO2 without a significant antitumor effect can exert excellent antitumor efficacy by responsively releasing ROS under the acidic TME to induce the mitochondria-mediated apoptosis via remarkable oxidative stress and simultaneously minimize damages to normal tissues. The current study presents a new concept of "efficacy-shaping nanomedicine" for the tumor-selective treatment of prostate cancer.

Antibody microarray profiling of osteosarcoma cell serum for identifying potential biomarkers.

The aim of the present study was to identify biomarkers in osteosarcoma (OS) cell serum by antibody microarray profiling, which may be used for OS diagnosis and therapy. An antibody microarray was used to detect the expression levels of cytokines in serum samples from 20 patients with OS and 20 healthy individuals. Significantly expressed cytokines in OS serum were selected when P<0.05 and fold change >2. An enzyme-linked immunosorbent assay (ELISA) was used to validate the antibody microarray results. Finally, classification accuracy was calculated by cluster analysis. Twenty one cytokines were significantly upregulated in OS cell serum samples compared with control samples. Expression of interleukin-6, monocyte chemoattractant protein-1, tumor growth factor-ß, growth-related oncogene, hepatocyte growth factor, chemokine ligand 16, Endoglin, matrix metalloproteinase-9 and platelet-derived growth factor-AA was validated by ELISAs. OS serum samples and control samples were distinguished by significantly expressed cytokines with an accuracy of 95%. The results demonstrated that expressed cytokines identified by antibody microarray may be used as biomarkers for OS diagnosis and therapy.