Deep learning based CETSA feature prediction cross multiple cell lines with latent space representation.

Mass spectrometry-coupled cellular thermal shift assay (MS-CETSA), a biophysical principle-based technique that measures the thermal stability of proteins at the proteome level inside the cell, has contributed significantly to the understanding of drug mechanisms of action and the dissection of protein interaction dynamics in different cellular states. One of the barriers to the wide applications of MS-CETSA is that MS-CETSA experiments must be performed on the specific cell lines of interest, which is typically time-consuming and costly in terms of labeling reagents and mass spectrometry time. In this study, we aim to predict CETSA features in various cell lines by introducing a computational framework called CycleDNN based on deep neural network technology. For a given set of n cell lines, CycleDNN comprises n auto-encoders. Each auto-encoder includes an encoder to convert CETSA features from one cell line into latent features in a latent space [Formula: see text]. It also features a decoder that transforms the latent features back into CETSA features for another cell line. In such a way, the proposed CycleDNN creates a cyclic prediction of CETSA features across different cell lines. The prediction loss, cycle-consistency loss, and latent space regularization loss are used to guide the model training. Experimental results on a public CETSA dataset demonstrate the effectiveness of our proposed approach. Furthermore, we confirm the validity of the predicted MS-CETSA data from our proposed CycleDNN through validation in protein-protein interaction prediction.

Fe-Ni Diatomic Sites Coupled with Pt Clusters to Boost Methanol Electrooxidation via Free Radical Relaying.

Pt-based catalysts for direct methanol fuel cells (DMFCs) are still confronted with the challenge of over-oxidation of Pt and poisoning effect of intermediates; therefore, a spatial relay strategy was adopted to overcome these issues. Herein, Pt clusters were creatively fixed on the N-doped carbon matrix with rich Fe-Ni diatoms, which can provide independent reaction sites for methanol oxidation reaction (MOR) and enhance the catalytic activity due to the electronic regulation effect between Pt cluster and atomic-level metal sites. The optimized Pt/FeNi-NC catalyst shows MOR electrocatalytic activity of 2.816 A mgPt -1 , 2.6 times that of Pt/C (1.115 A mgPt -1 ). Experiments combined with DFT study reveal that Fe-Ni diatoms and Pt clusters take charge of hydroxyl radical (⋅OH) generation and methanol activation, respectively. The free radical relaying of ⋅OH could prevent the over-oxidation of Pt. Meanwhile, ⋅OH from Fe-Ni sites accelerates the elimination of intermediates, thus improving the durability of catalysts.

CycleDNN - A Novel Deep Neural Network Model for CETSA Feature Prediction cross Cell Lines.

Cellular Thermal Shift Assay (CETSA) has been widely used in drug discovery, cancer cell biology, immunology, etc. One of the barriers for CETSA applications is that CETSA experiments have to be conducted on various cell lines, which is extremely time-consuming and costly. In this study, we make an effort to explore the translation of CETSA features cross cell lines, i.e., known CETSA feature of a given protein in one cell line, can we automatically predict the CETSA feature of this protein in another cell line, and vice versa? Inspired by pix2pix and CycleGAN, which perform well on image-to-image translation cross various domains in computer vision, we propose a novel deep neural network model called CycleDNN for CETSA feature translation cross cell lines. Given cell lines A and B, the proposed CycleDNN consists of two auto-encoders, the first one encodes the CETSA feature from cell line A into Z in the latent space [Formula: see text], then decodes Z into the CETSA feature in cell line B., Similarly, the second one translates the CETSA feature from cell line B to cell line A through the latent space [Formula: see text]. In such a way, the two auto-encoders form a cyclic feature translation between cell lines. The reconstructed loss, cycle-consistency loss, and latent vector regularization loss are used to guide the training of the model. The experimental results on a public CETSA dataset demonstrate the effectiveness of the proposed approach.

Deep Learning-Based Multimodal 3 T MRI for the Diagnosis of Knee Osteoarthritis.

The objective of this study was to investigate the application effect of deep learning model combined with different magnetic resonance imaging (MRI) sequences in the evaluation of cartilage injury of knee osteoarthritis (KOA). Specifically, an image superresolution algorithm based on an improved multiscale wide residual network model was proposed and compared with the single-shot multibox detector (SSD) algorithm, superresolution convolutional neural network (SRCNN) algorithm, and enhanced deep superresolution (EDSR) algorithm. Meanwhile, 104 patients with KOA diagnosed with cartilage injury were selected as the research subjects and underwent MRI scans, and the diagnostic performance of different MRI sequences was analyzed using arthroscopic results as the gold standard. It was found that the image reconstructed by the model in this study was clear enough, with minimum noise and artifacts, and the overall quality was better than that processed by other algorithms. Arthroscopic analysis found that grade I and grade II lesions concentrated on patella (26) and femoral trochlear (15). In addition to involving the patella and femoral trochlea, grade III and grade IV lesions gradually developed into the medial and lateral articular cartilage. The 3D-DS-WE sequence was found to be the best sequence for diagnosing KOA injury, with high diagnostic accuracy of over 95% in grade IV lesions. The consistency test showed that the 3D-DESS-WE sequence and T2∗ mapping sequence had a strong consistency with the results of arthroscopy, and the Kappa consistency test values were 0.748 and 0.682, respectively. In conclusion, MRI based on deep learning could clearly show the cartilage lesions of KOA. Of different MRI sequences, 3D-DS-WE sequence and T2∗ mapping sequence showed the best diagnosis results for different degrees of KOA injury.

Comparison of apixaban and rivaroxaban for anticoagulant effect after lumbar spine surgery: a single-center report.

AIM: To compare efficacy and safety of anticoagulants apixaban and rivaroxaban after lumbar spine surgery retrospectively. METHODS: In this study comprising 480 patients, lower-limb swelling, deep venous thrombosis, pulmonary embolism, blood loss, ecchymosis and D-dimer changes were observed. RESULTS: The changes in perimeter of the legs were tested, and significant differences were noted 10 cm above the patella, but no significant differences 10 cm below the patella. Twelve thrombotic events occurred in the apixaban group and nine in rivaroxaban group. No significant difference in the incidences of thromboembolic events (p = 1.00). Compared with rivaroxaban, there was significantly less bleeding in the apixaban group (p = 0.03). CONCLUSION: Apixaban and rivaroxaban were equally effective anticoagulation therapies that exhibited similar preventive effects against postoperative venous thromboembolism after lumbar spine surgery.

Research and application of absorbable screw in orthopedics: a clinical review comparing PDLLA screw with metal screw in patients with simple medial malleolus fracture.

OBJECTIVE: To observe the therapeutic effect of absorbable screw in medial malleolus fracture and discuss its clinical application in orthopedics. METHODS: A total of 129 patients with simple medial malleolus fracture were studied. Among them, 64 patients were treated with poly-D, L-lactic acid (PDLLA) absorbable screws, while the others were treated with metal screws. All the patients were followed up for 12-20 months (averaged 18.4 months) and the therapeutic effect was evaluated according to the American Orthopaedic Foot and Ankle Society clinical rating systems. RESULTS: In absorbable screw group, we obtained excellent and good results in 62 cases (96.88%); in steel screw group, 61 cases (93.85%) achieved excellent and good results. There was no significant difference between the two groups. CONCLUSION: In the treatment of malleolus fracture, absorbable screw can achieve the same result compared with metal screw fixation. Absorbable screw is preferred due to its advantages of safety, cleanliness and avoiding the removal procedure associated with metallic implants.

Knockdown of Mad2 induces osteosarcoma cell apoptosis-involved Rad21 cleavage.

BACKGROUND: Besides Mad2's role in carcinogenesis, recent study has shown that it is essential in cell survival. Here we found that knockdown of Mad2 causes osteosarcoma cell death through apoptosis, with the apoptotic signal resulting from Rad21 cleavage. METHODS: U2OS and MG63 cells were divided into three groups: the Mad2 siRNA group, mock group and normal control group; the Mad2 siRNA group and mock group are transfected with Mad2 shRNA plasmid and mock plasmid, respectively. G418 was used to increase the transfection efficacy, which was evaluated by GFP fluorescence. Quantitative PCR and Western blotting analyses were used to detect the transcription and expression of Mad2, Rad21 and caspase-3, respectively. Flow cytometry assay using PE-labeled Annexin-V and PI, TUNEL assay and Hoechst 33258 staining were used to evaluate cell apoptosis. RESULTS: We successfully achieved knockdown of Mad2 expression in cancer cells using RNA interference. We observed obvious apoptosis in the Mad2 siRNA group compared with the Mock and control group. We found that the apoptosis induced by Mad2 knockdown correlated with Rad21 cleavage. CONCLUSION: These results confirmed that knockdown of Mad2 causes osteosarcoma cell death through apoptosis and provides evidence that the apoptotic signal resulted from Rad21 cleavage. This study suggested that Mad2 has potential to be a novel target for cancer therapy.

Fusion between cancer cells and myofibroblasts is involved in osteosarcoma.

Communication between cancer cells and the microenvironment appears to be an important determinant of disease prognosis. However, the detailed mechanisms of the interactions between cancer cells and surrounding cells have yet to be clarified. Recent studies on cell fusion have indicated this interaction to be one of the driving forces in cancer progression. Fibroblasts constitute a significant component of the carcinoma stromal compartment. Many of these fibroblasts are thought to differentiate into myofibroblasts, which are characterized by a positive expression of α-smooth muscle actin. Expression of α-smooth muscle actin in osteosarcoma was evaluated, and was observed to be excessive in the multinucleated osteoclast-like giant cells in osteosarcoma tissue, indicating the possibility of cell fusion between cancer cells and myofibroblasts. In order to test the above hypothesis, we first transformed the primary mouse embryonic fibroblast cells into activated myofibroblast cells. Osteosarcoma cells were then co-cultured with mouse myofibroblast cells, and cell fusion was investigated using species-specific chromosomal markers. Expression of α-smooth muscle actin was successfully induced in primary mouse embryonic fibroblast cells. Cells fused spontaneously with a fusion rate of approximately 1-2% and fusion between more than two cells was also observed. Our study demonstrated that fusion between cancer cells and myofibroblasts may contribute to the observed multinucleated giant cells in osteosarcoma. We posit that cell fusion is a novel mechanism for the interaction between cancer cells and the microenvironment.

Clinical efficacy of artificial skin combined with vacuum sealing drainage in treating large-area skin defects.

OBJECTIVE: To observe the clinical efficacy of artificial skin combined with vacuum sealing drainage (VSD) in treating large-area skin defects. METHODS: Totally 18 patients with skin defects, treated with artificial skin combined with VSD from September 2008 to May 2009 in our hospital, were retrospectively analyzed in this study. There were 15 males and 3 females, aged 7-66 years, 34.3 years on average. Among them, 10 cases had skin laceration caused by traffic accidents (7 with open fractures), 1 mangled injury, 1 blast injury, 1 stump infection combined with skin defects after amputation and 5 heel ulcers. RESULTS: All skin grafts in 16 cases survived after being controlled by VSD for one time. For the rest 2 patients, one with skin avulsion on the left foot was given median thickness skin grafts after three times of VSD, the other with open fractures in the left tibia and fibula caused by a traffic accident was given free flap transplantation. Skin grafts of both patients survived, with normal color and rich blood supply. CONCLUSION: Skin grafting in conjunction with artificial skin and VSD is much more effective than traditional dressing treatment and worth wide application in clinic.

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a novel delivery system for parathyroid hormone-related protein 1-34.

Chitosan (CS) and epoxy propyl trimethyl ammonium chloride (EPTAC) were used to prepare the water-soluble N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC). HTCC and sodium tripolyphosphate (TPP) were mixed to form HTCC nanoparticles based on ionic gelation. Parathyroid hormone-related protein 1-34 (PTHrP1-34) was incorporated into the HTCC nanoparticles. The particle size and morphology of nanoparticles were determined by transmission electron microscopy (TEM). HTCC/PTHrP1-34 nanoparticles were 100-180 nm in size and their encapsulation efficiency and loading capacity were related to HTCC concentration, TPP concentration and initial concentration of PTHrP1-34. Relatively optimum encapsulation efficiency (78.4%) and loading capacity (13.7%) of PTHrP1-34 is achieved, and the in vitro release profile of PTHrP1-34 from nanoparticles has an initial burst, which is followed up by a slow release phase. These studies showed that HTCC/PTHrP1-34 nanoparticles are suitable for the treatment of osteoporosis, because of their slow-continuous-release properties, and the relevant in vivo experiments and clinical trials should be further studied.

Mitotic arrest defective protein 2 expression abnormality and its clinicopathologic significance in human osteosarcoma.

Osteosarcoma is the most common primary malignancy of bone. Overexpression of mitotic arrest defective protein 2 (MAD2) is found in many human neoplasms, but its role in the oncogenesis of osteosarcoma is an untouched topic. The objective of this research was to observe the expression of MAD2 in human osteosarcoma and explore its clinicopathologic significance. MAD2 expression was analyzed in 48 primary osteosarcoma cases (19 osteoblastic osteosarcomas, 17 chondroblastic osteosarcomas and 12 fibroblastic osteosarcomas) using immunohistochemistry. A total of 20 normal bone specimens formed a control group. MAD2 was commonly overexpressed in human osteosarcoma. Immunopositivity was higher in tumors with lower differentiation and higher clinical stage. Increased expression of MAD2 was associated with earlier metastasis and poorer survival. Our findings provide evidence that MAD2 contributes to the pathogenesis and development of human osteosarcoma, Testing may have a clinical role in predicting prognosis, selecting appropriate chemotherapeutic strategies and providing novel strategies for osteosarcoma therapy.

Purification and Characterization of a Novel 21 kD Calcium-binding Protein from Rabbit Appendix Lymphocytes.

A novel 21 kD calcium-binding protein from rabbit appendix B lymphocytes has been purified and characterized. Through heat-denaturation, using Phenyl-Sepharose and DEAE-Sepharose chromatography, we obtained 5.3 mg SDS-PAGE homogeneous CaBP(21) from 1 kg lymphocyte cells. Amino acid analysis showed the acidic amino acid content (Asp + Glu) to be 26% after HCL hydrolysis. The blocking of the N-terminus of CaBP(21) prevents the de novo Edman degradation, like most of the other calcium-binding proteins. CaBP(21) has 46% of hydrophobic amino acid (with Gly, without Trp) content, 10% of basic amino acid content and 44% of acidic and polar amino acids. Peptide mapping and SDS-PAGE combined Sephadex G-25 gel filtration proves that CaBP(21) consists of two identical or similar subunits. Ca(2+)-binding assays using Arsenazo III indicated one protein to bind 4 Ca(2+) with dissociation constant (K(d)) for Ca(2+) about 10(-5) mol/L.