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Thrombospondin‐1 (TSP1) is generally assumed to suppress the growth of osteosarcoma through inhibiting angiogenesis; however, it is unclear whether TSP1 could affect the antitumor immunity against osteosarcoma. We aimed to explore the immune‐related tumor‐promoting effects of TSP1 and decipher its underlying mechanism. First, we identified that TSP1 regulated programmed death‐ligand 1 (PD‐L1) expression, which was related to the CD8+ T cells anergy in osteosarcoma cells. The exact role of PD‐L1 in the immunosuppressive effect of TSP1 was then further confirmed by the addition of the PD‐L1 neutralizing Ab. With the addition of PD‐L1 neutralizing Abs during cocultivation, the inhibition of CD8+ T cells was abolished to a certain extent. Further mechanistic investigations showed that TSP1‐induced PD‐L1 upregulation was achieved by activation of the signal transducer and activator of transcription 3 (STAT3) pathway. In vivo experiments also indicated that TSP1 overexpression could promote the growth of primary lesions, whereas TSP1 knockdown effectively inhibits the growth of the primary lesion as well as lung metastasis by restoring the antitumor immunity. Thrombospondin‐1 knockdown combined with PD‐L1 neutralizing Ab achieved a more pronounced antitumor effect. Taken together, our study showed that TSP1 upregulates PD‐L1 by activating the STAT3 pathway and, therefore, impairs the antitumor immunity against osteosarcoma. [ABSTRACT FROM AUTHOR]

Raman hyperspectral imaging is a powerful method to obtain detailed chemical information about a wide variety of organic and inorganic samples noninvasively and without labels. However, due to the weak, nonresonant nature of spontaneous Raman scattering, acquiring a Raman imaging dataset is time-consuming and inefficient. In this paper we utilize a compressive imaging strategy coupled with a context-aware image prior to improve Raman imaging speed by 5- to 10-fold compared to classic point-scanning Raman imaging, while maintaining the traditional benefits of point scanning imaging, such as isotropic resolution and confocality. With faster data acquisition, large datasets can be acquired in reasonable timescales, leading to more reliable downstream analysis. On standard samples, context-aware Raman compressive imaging (CARCI) was able to reduce the number of measurements by ∼85% while maintaining high image quality (SSIM >0.85). Using CARCI, we obtained a large dataset of chemical images of fission yeast cells, showing that by collecting 5-fold more cells in a given experiment time, we were able to get more accurate chemical images, identification of rare cells, and improved biochemical modeling. For example, applying VCA to nearly 100 cells' data together, cellular organelles were resolved that were not faithfully reconstructed by a single cell's dataset. [ABSTRACT FROM AUTHOR]

Current flow‐based blood counting devices require expensive and centralized medical infrastructure and are not appropriate for field use. In this article we report a streamlined, easy‐to‐use method to count red blood cells (RBC), white blood cells (WBC), platelets (PLT) and 3‐part WBC differential through a cost‐effective and automated image‐based blood counting system. The approach consists of using a compact, custom‐built microscope with large field‐of‐view to record bright‐field and fluorescence images of samples that are diluted with a single, stable reagent mixture and counted using automatic algorithms. Sample collection utilizes volume‐controlled capillary tubes, which are then dropped into a premixed, shelf‐stable solution to stain and dilute in a single step. Sample measurement and analysis are fully automated, requiring no input from the user. Cost of the system is minimized through the use of custom‐designed motorized components. We compare the performance of our system, as operated by trained and untrained users, to the clinical gold standard on 120 adult blood samples, demonstrating agreement within Clinical Laboratory Improvement Amendments guidelines, with no statistical difference in performance among different operator groups. The system's cost‐effectiveness, automation and performance indicate that it can be successfully translated for use in low‐resource settings where central hematology laboratories are not accessible. [ABSTRACT FROM AUTHOR]

The SOX4 transcription factor is involved in various cellular processes, such as embryonic development and differentiation. Deregulated expression of Sox4 in several human cancers has been reported to date, but its biological functions in the progression of osteosarcoma remain unclear. In this study, we found that the expression levels of SOX4 protein were significantly higher in high-grade osteosarcoma tissues and metastatic osteosarcoma tissues. Its overexpression was associated with poor prognosis in osteosarcoma. Knockdown of the SOX4 gene in the osteosarcoma cell lines resulted in decreased cell proliferation, migration, invasion, and induced apoptosis. After SOX4 gene silencing, the protein expression levels of Bax, Caspase-3, and P53 in osteosarcoma cells were significantly elevated, while the protein expression levels of Bcl-2, MMP2, and MMP9 were obviously decreased. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor oncogene in the regulation of osteosarcoma cell proliferation, apoptosis, and invasion, and it may be a potential target for effective osteosarcoma therapy. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase ( FAK) overexpression is related to invasive and metastatic properties in different kinds of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatments, but its effect in human osteosarcoma has not been well studied. In the present study, we analyzed the antitumor efficacy of PF562271, an FAK inhibitor, against osteosarcoma in vitro and in vivo. Phosphorylated FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed proliferation and colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired the tube formation ability of endothelial cells in vitro. Finally, oral treatment with PF562271 in mice dramatically reduced tumor volume, weight, and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Humeral shaft fractures are generally managed with the conventional posterior open reduction and internal fixation (ORIF) or minimally invasive plate osteosynthesis (MIPO). This study was aimed at comparing the outcomes of these surgical techniques in terms of the vascular integrity of the mid-distal humeral shaft.Methods: Twelve upper limbs were harvested from 6 fresh cadavers. ORIF or MIPO was randomly performed on either side of each pair of limbs. The axillary artery was perfused with a latex-lead tetraoxide red solution to visualize the vascular structures. The vascular integrity of the humerus was examined by plain radiography and dissection. The periosteal filling achieved with each technique was scored and the scores compared.Results: In each limb, one main nutrient artery entering the mid-distal humeral shaft anteromedially (83.3 %) or medially (16.7 %) was first identified. No case of injury to the main nutrient artery was noted for either surgical technique. Injuries to the accessory nutrient arteries entering the mid-distal humeral shaft from the posterior aspect were absent in the MIPO cases, but occurred in 52.9 % of the ORIF cases. In addition, MIPO was also superior to the open plate technique showed superior periosteal filling than.Conclusions: Our results showed that the MIPO technique is superior to the ORIF in terms of preserving the vascular integrity of the mid-distal humeral shaft. [ABSTRACT FROM AUTHOR]

Objective: To explore the effectiveness of proximal femoral nail antirotation (PFNA) combined with mini plate for reconstruction of lateral femoral wall in the treatment of type AO/Orthopaedic Trauma Association (AO/OTA) type 31-A3 intertrochanteric fracture., Methods: The clinical data of 70 elderly patients with AO/OTA type 31-A3 intertrochanteric fracture treated between January 2013 and January 2018 were retrospectively analyzed. They were divided into group A (PFNA alone, 35 cases) and group B (PFNA combined with mini plate reconstruction of lateral femoral wall, 35 cases). There was no significant difference in the general data of gender, age, side, cause of injury, time from injury to operation between the two groups ( P >0.05). The operation time, intraoperative blood loss, fracture healing time, postoperative complications, and the tip apex distance (TAD) at 2 months after operation were recorded and compared between the two groups. Harris hip score was used to evaluate the function at 12 months after operation., Results: Both groups were followed up 9-21 months, with an average of 16.6 months. The operation time and intraoperative blood loss in group A were significantly less than those in group B ( P <0.05); there was no significant difference in TAD between the two groups at 2 months after operation ( t =0.096, P =0.462). There were 5 complications (14.3%) occurred in group A, including 2 cases of blade perforating from the hip joint, 2 cases of screw back out, and 1 case of bone nonunion; only 1 case (2.9%) in group B had screw back out after operation; there was no significant difference in the incidence of complications between the two groups ( χ 2 =2.917, P =0.088). All the fracture healed in group B, and 1 patient in group A suffered bone nonunion and eventually main nail fracture. The healing time of fracture in group A [(15.6±2.7) weeks] was significantly longer than that in group B [(12.5±2.5) weeks], showing significant difference ( t =2.064, P =0.023). At 12 months after operation, according to Harris score, the results were excellent in 5 cases, good in 9 cases, fair in 13 cases, and poor in 8 cases in group A, the qualified rate (Harris score>70) was 77.14%; and the results were excellent in 7 cases, good in 11 cases, fair in 16 cases, and poor in 1 case in group B, the qualified rate was 97.14%; there was significant difference in the qualified rate between the two groups ( χ 2 =6.248, P =0.012)., Conclusion: Compared with PFNA alone, the treatment of AO/OTA type 31-A3 intertrochanteric fracture with PFNA combined with mini plate reconstruction of lateral femoral wall can significantly reduce postoperative complications, promote fracture healing, and improve functional recovery of patients after operation.