7,8-DHF inhibits BMSC oxidative stress via the TRKB/PI3K/AKT/NRF2 pathway to improve symptoms of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMO) is characterized by bone loss and microstructural damage, and it is most common in older adult women. Currently, there is no cure for PMO. The flavonoid chemical 7,8-dihydroxyflavone (7,8-DHF) specifically activates tropomyosin receptor kinase B (TRKB). Furthermore, 7,8-DHF has various biological characteristics, including anti-inflammatory and antioxidant effects. However, the specific implications and fundamental mechanisms of 7,8-DHF in PMO remain unclear. We used protein imprinting, flow cytometry, tissue staining, and other methods to estimate the preventive mechanisms of 7,8-DHF against hydrogen peroxide (H2O2)-induced apoptosis in primary mouse bone marrow mesenchymal stem cells (BMSCs), osteogenic differentiation ability, and bone mass in ovariectomized (OVX) mice. We found that 7,8-DHF effectively prevented H2O2-induced reductions in the viability and osteogenic differentiation capacity of primary BMSCs. Mechanistically, 7,8-DHF induced the TRKB to activate the PI3K/AKT/NRF2 pathway. In vivo experiments with the OVX mouse model confirmed that 7,8-DHF can inhibit oxidative stress and promote bone formation, indicating that 7,8-DHF improves the viability and osteogenic differentiation ability of BMSCs stimulated via H2O2 by activating the TRKB/PI3K/AKT and NRF2 pathways, thereby improving PMO.

Deep Learning Based Automatic Left Ventricle Segmentation from the Transgastric Short-Axis View on Transesophageal Echocardiography: A Feasibility Study.

Segmenting the left ventricle from the transgastric short-axis views (TSVs) on transesophageal echocardiography (TEE) is the cornerstone for cardiovascular assessment during perioperative management. Even for seasoned professionals, the procedure remains time-consuming and experience-dependent. The current study aims to evaluate the feasibility of deep learning for automatic segmentation by assessing the validity of different U-Net algorithms. A large dataset containing 1388 TSV acquisitions was retrospectively collected from 451 patients (32% women, average age 53.42 years) who underwent perioperative TEE between July 2015 and October 2023. With image preprocessing and data augmentation, 3336 images were included in the training set, 138 images in the validation set, and 138 images in the test set. Four deep neural networks (U-Net, Attention U-Net, UNet++, and UNeXt) were employed for left ventricle segmentation and compared in terms of the Jaccard similarity coefficient (JSC) and Dice similarity coefficient (DSC) on the test set, as well as the number of network parameters, training time, and inference time. The Attention U-Net and U-Net++ models performed better in terms of JSC (the highest average JSC: 86.02%) and DSC (the highest average DSC: 92.00%), the UNeXt model had the smallest network parameters (1.47 million), and the U-Net model had the least training time (6428.65 s) and inference time for a single image (101.75 ms). The Attention U-Net model outperformed the other three models in challenging cases, including the impaired boundary of left ventricle and the artifact of the papillary muscle. This pioneering exploration demonstrated the feasibility of deep learning for the segmentation of the left ventricle from TSV on TEE, which will facilitate an accelerated and objective alternative of cardiovascular assessment for perioperative management.

Chitosan Microspheres Loaded with Curcumin and Gallic Acid: Modified Synthesis, Sustainable Slow Release, and Enhanced Biological Property.

Improving the utilization rate of loaded-drugs is of huge importance for generating chitosan-based (CS) micro-carriers. This study aims to fabricate a novel CS microspheres co-delivered curcumin (Cur) and gallic acid (Ga) to assess drug loading and release kinetics, the blood compatibility and anti-osteosarcoma properties. The present study observes the interaction between CS and Cur/Ga molecules and estimates the change in crystallinity and loading and release rate. In addition, blood compatibility and cytotoxicity of such microspheres are also evaluated. Cur-Ga-CS microspheres present high entrapment rate of (55.84 ± 0.34) % for Ga and (42.68 ± 0.11) % for Cur, possibly attributed to surface positive charge (21.76 ± 2.46) mV. Strikingly, Cur-Ga-CS microspheres exhibit slowly sustainable release for almost 7 days in physiological buffer. Importantly, these microspheres possess negligibly toxic to blood and normal BMSC cells, but strong anti-osteosarcoma effect on U2OS cells. Overall, Cur-Ga-CS microspheres are promising to become a novel anti-osteosarcoma agent or sustainable delivery carrier in biomedical applications.

Effect study of exosomes derived from platelet-rich plasma in the treatment of knee cartilage defects in rats.

BACKGROUND: The repair of articular cartilage defects has always been a difficult problem. We aimed to investigate the therapeutic effect of intra-articular injection of platelet-rich plasma (RPR) and PRP-derived exosomes (PRP-Exos) on cartilage defects in rat knee joints and then provide experience for the use of PRP-exos in cartilage defect repair. METHODS: Rat abdominal aortic blood was collected, and PRP was extracted by two-step centrifugation. PRP-exos were obtained by kit extraction, and PRP-exos were identified by various methods. After the rats were anesthetized, a cartilage defect subchondral bone was created at the proximal end of the origin of the femoral cruciate ligament with a drill. SD rats were divided into 4 groups, including PRP group, 50 µg/ml PRP-exos group, 5 µg/ml PRP-exos group, and control group. One week after the operation, 50 µg/ml PRP, 50 µg/ml PRP-exos, 5 µg/ml PRP-exos and normal saline were injected into the knee joint cavity of rats in each group, once a week. A total of two injections were given. On the 5th and 10th week after drug injection, the serum levels of matrix metalloproteinase 3 (MMP-3) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) were detected by each treatment method, respectively. The rats were killed at the 5th and 10th weeks, respectively, and the cartilage defect repair was observed and scored. The defect repair tissue sections were used for HE staining and type II collagen immunohistochemical staining. RESULTS: The histological results showed that both PRP-exos and PRP could promote cartilage defect repair and type II collagen formation, and the promoting effect of PRP-exos was significantly better than that of PRP. In addition, enzyme-linked immunosorbent assay (ELISA) results showed that compared with PRP, PRP-exos could significantly increase serum TIMP-1 and decrease serum MMP-3 in rats. And the promoting effect of PRP-exos was concentration dependent. CONCLUSION: Intra-articular injection of PRP-exos and PRP can promote the repair of articular cartilage defects, and the therapeutic effect of PRP-exos is better than the same concentration of PRP. PRP-exos are expected to be an effective treatment for cartilage repair and regeneration.

Performance improvement of space-resolved extreme ultraviolet spectrometer by use of complementary metal-oxide semiconductor detectors at the Experimental Advanced Superconducting Tokamak.

Two pairs of space-resolved extreme ultraviolet (EUV) spectrometers working at 5-138 Å with different vertical observation ranges of -7 ≤ Z ≤ 19 and -18 ≤ Z ≤ 8 cm have been newly developed to observe the radial profile of impurity line emissions and to study the transport of high-Z impurity ions intrinsically existing in EAST tokamak plasmas. Both spectrometers are equipped with a complementary metal-oxide semiconductor (CMOS) detector (Andor Marana-X 4.2B-6, Oxford Instruments) with sensitive area of 13.3 × 13.3 mm2 and number of pixels equal to 2048 × 2048 (6.5 × 6.5 µm2/pixels). Compared to the currently operating space-resolved EUV spectrometers with a charge-coupled detector (CCD: 1024 × 255 pixels, 26 × 26 µm2) working at 30-520 Å, this spectrometer's performance was substantially improved by using the CMOS detector. First, the spectral resolution measured at full width at half maximum was improved in the whole wavelength range, e.g., Δλ1/2_CMOS = 0.092 Å and Δλ1/2_CCD = 0.124 Å at C VI 33.73 Å and Δλ1/2_CMOS = 0.104 Å and Δλ1/2_CCD = 0.228 Å at Mo XXXI 115.999 Å, thus enabling a more accurate analysis of spectra with complicated structure such as tungsten unresolved transition array in the range 45-65 Å. Second, the temporal resolution was largely improved due to the high-speed data acquisition system of the CMOS detector, e.g., Δt_CMOS = 15 ms/frame and Δt_CCD = 200 ms/frame at routine operation in the radial profile measurement. Third, signal saturation issues that occurred when using the old CCD sensor during impurity accumulation now disappeared entirely using the CMOS detector due to lower exposure time at high readout rates, which largely improved the observation performance in similar impurity burst events. The above-mentioned performance improvements of the space-resolved EUV spectrometer led to a rapid change in the W XXXIII (52.22 Å) radial profile during a single cycle of low-frequency sawtooth oscillation with fst = 5-6 Hz at a sufficient detector count rate.