LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.

BACKGROUND: Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is of much significance for bone formation, the imbalance of it would result in osteoporosis and other pathological bone defects. Increasing evidences showed that long non-coding RNAs (lncRNAs) and miRNAs played vital roles in the regulation of osteogenic differentiation. LncRNA KCNQ1OT1 was often regarded as an imprinted lncRNA and was related to tumor progression, while its function in osteogenic differentiation remained unclear. METHOD: qRT-PCR was performed to detect the expression of KCNQ1OT1, miR-214 and osteogenesis-related genes BMP2, Runx2, OPN, and OCN. Western blotting was carried out to detect osteogenesis-related markers. The osteoblastic phenotype was evidenced by alkaline phosphatase (ALP) activity and Alizarin Red S accumulation detection. Bioinformatics and luciferase assays were used to predict and validate the interaction between KCNQ1OT1 and miR-214 as well as BMP2 and miR-214. RESULTS: KCNQ1OT1 was significantly up-regulated during the process of osteogenic induction while miR-214 was contrarily down-regulated. Knockdown of KCNQ1OT1 inhibited osteogenic differentiation and down-regulated BMP2 and osteogenesis-related genes. It was also confirmed that KCNQ1OT1 directly interacted with miR-214. Meanwhile, miR-214 could bind to 3'UTR of BMP2 and therefore inhibited its expression. Furthermore, co-transfection of miR-214 inhibitor could rescue the down-regulation of BMP2 and osteogenesis-related genes and osteogenic differentiation suppression induced by KCNQ1OT1 knockdown. Moreover, miR-214 inhibitor significantly reversed the decreased protein levels of p-Smad1/5/8, Runx2 and Osterix induced by shKCNQ1OT1. CONCLUSIONS: KCNQ1OT1 positively regulated osteogenic differentiation of BMSCs by acting as a ceRNA to regulate BMP2 expression through sponging miR-214.

How to optimize the therapeutic effect of free autogenous fibula graft and wrist arthroplasty for giant cell tumors of distal radius?

OBJECTIVE: The purpose of this study is to retrospectively analyze the clinical efficacy of free fibula autograft and wrist arthroplasty in the treatment of giant cell tumors (GCT) of distal radius. METHODS: We retrospectively reviewed 26 patients with GCT of distal radius who underwent free autogenous fibula graft and wrist arthroplasty for repairing residual defect after en-block resection. The length of the fibula graft was 8.2 cm (6-10 cm). Postoperative follow-up regularly for an mean of 66.9 months. Bone healing was assessed by radiographs, pain was assessed by Visual Analog Scale (VAS) score and limb function was evaluated by Musculoskeletal Tumor Society (MSTS) score and disabilites of the arm, shoulder and hand (DASH) score. The range of motion (ROM) of wrist and grip strength were also evaluated. RESULT: There were four males and 22 females with an mean age of 36.7 years (19-60 years); the mean length of lesions was 4.8 cm (2.3-6.6 cm); 21 primary cases and five recurrent cases; eight cases of Campanacci Grade II, 18 cases of Grade III. We had no postoperative lung metastasis and only one case had a local recurrence, three cases (11%) with subluxation of lower ulnoradial joints and five cases (19%) showed narrowing of wrist joint space. The mean postoperative VAS pain score was 0.7 ± 0.7 and grip strength retained 71% of the normal hand, MSTS score was 27.7 ± 1.1 and DASH score was 9.0 ± 3.7. The ROM of the involved wrist only slightly restricted and no donor complications. Postoperative wrist joint function was significantly improved. CONCLUSION: Strict surgical resection boundary and solid reconstruction of wrist joint capsule are the key to achieving excellent oncological prognosis and function of distal radius GCT.

Rupture of posterior cruciate ligament leads to radial displacement of the medial meniscus.

BACKGROUND: To explore the association between the rupture of posterior cruciate ligament (PCL) and the radial displacement of medial meniscus under the conditions of different flexion and various axial loads. METHODS: The radial displacement value of medial meniscus was measured for the specimens of normal adult knee joints, including 12 intact PCLs, 6 ruptures of the anterolateral bundle (ALB), 6 ruptures of the postmedial bundle (PMB), and 12 complete ruptures. The measurement was conducted at 0°, 30°, 60°, and 90° of knee flexion angles under 200 N, 400 N, 600 N, 800 N and 1000 N of axial loads respectively. RESULTS: The displacement values of medial meniscus of the ALB rupture group increased at 0° flexion under 800 N and 1000 N, and at 30°, 60° and 90° flexion under all loads in comparison with the PCL intact group. The displacement values of the PMB rupture group was higher at 0° and 90° flexion under all loads, and at 30° and 60° flexion under 800 N and 1000 N loads. The displacement of the PCL complete rupture group increased at all flexion angles under all loads. CONCLUSIONS: Either partial or complete rupture of the PCL can increase in the radial displacement of the medial meniscus, which may explain the degenerative changes that occuring in the medial meniscus due to PCL injury. Therefore, early reestablishment of the PCL is necessarily required in order to maintain stability of the knee joint after PCL injury.

Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration.

MYBL2 (MYB proto-oncogene like 2) is an emerging prognostic marker for malignant tumors, and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated. We constructed a transcription factor activity profile of osteosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus. Subsequently, we calculated the extent of MYBL2 activation in malignant proliferative osteoblasts. We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma. Furthermore, we systematically correlated MYBL2 with immunological signatures in the tumor microenvironment in pan-cancer, including immune cell infiltration, immune checkpoints, and tumor immunotherapy prognosis. Finally, we developed and validated a risk score (MRGS), derived an osteosarcoma risk score nomogram based on MRGS, and tested its ability to predict prognosis. MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways. MYBL2 expression positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines. Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived suppressor cells, Th2 cell infiltration, CD276, RELT gene expression, and tumor mutation burden. In summary, MYBL2 regulates proliferation, progression, and immune infiltration in osteosarcoma and pan-cancer. Therefore, we found that MYBL2 could be used as a potential marker for predicting the osteosarcoma prognosis. Patients with osteosarcoma and high MYBL2 expression are theoretically more sensitive to methotrexate. An osteosarcoma prognostic nomogram can provide new ideas in the search for osteosarcoma prognostic markers.

Charge-mode Neural Stimulator with a Capacitor-reuse Residual Charge Detector and Active Charge Balancing for Epileptic Seizure Suppression.

This study proposes a charge-mode neural stimulator for electrical stimulation systems that utilizes a capacitor-reuse technique with a residual charge detector and achieves active charge balancing simultaneously. The design is mainly used for epilepsy suppression systems to achieve real-time symptom relief during seizures. A charge-mode stimulator is adopted in consideration of the complexity of circuit design, the high voltage tolerance of transistors, and system integration requirements in the future. The residual charge detector allows users to understand the current stimulus situation, enabling them to make optimal adjustments to the stimulation parameters. On the basis of the information on actual stimulation charge, active charge balancing can effectively prevent the accumulation of mismatched charges on electrode impedance. The capacitor- and phase-reuse techniques help realize high integration of the overall stimulator circuit in consideration of the commonality of the use of a capacitor and charging/discharging phase in the stimulation circuit and charge detector. The proposed charge-mode neural stimulator is implemented in a TSMC 0.18 µm 1P6M CMOS process with a core area of 0.2127 mm2. Measurement results demonstrate the accuracy of the stimulation's functionality and the programmable stimulus parameters. The effectiveness of the proposed charge-mode neural stimulator for epileptic seizure suppression is verified through animal experiments.

Inhibition of histone deacetylases potentiates BMP9-induced osteogenic signaling in mouse mesenchymal stem cells.

BACKGROUND/AIMS: We have demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent BMPs in regulating osteoblast differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism underlying BMP9-induced osteogenesis remains to be fully elucidated. It is known that epigenetic regulations play an important role in regulating the stem cell potency and lineage commitment. Here, we investigate if the inhibition of histone deacetylases (Hdacs) affects BMP9-induced osteogenic differentiation of MSCs. METHODS: Using the Hdac inhibitor trichostatin A (TSA), we assess that TSA enhances BMP9-mediated osteogenic markers and matrix mineralization in MSCs, and bone formation in mouse embryonic limb explants. RESULTS: We find that the endogenous expression of most of the 11 Hdacs is readily detectable in MSCs. BMP9 is shown to induce most Hdacs in MSCs. We demonstrate that TSA potentiates BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs, as well as late osteogenic markers osteopontin (OPN) and osteocalcin (OCN) and matrix mineralization. Fetal limb explant culture studies reveal that TSA potentiates BMP9-induced endochondral bone formation, possibly by expanding hypertrophic chondrocyte zone of growth plate. CONCLUSION: Our findings strongly suggest histone deacetylases may play an important role in fine-tuning BMP9-mediated osteogenic signaling through a negative feedback network in MSCs. Thus, Hdac inhibitors may be used as novel therapeutics for bone fracture healing.

Destabilization of heterologous proteins mediated by the GSK3ß phosphorylation domain of the ß-catenin protein.

BACKGROUND AND AIMS: Wnt/ß-catenin signaling plays important roles in development and cellular processes. The hallmark of canonical Wnt signaling activation is the stabilization of ß-catenin protein in cytoplasm and/or nucleus. The stability of ß-catenin is the key to its biological functions and is controlled by the phosphorylation of its amino-terminal degradation domain. Aberrant activation of ß-catenin signaling has been implicated in the development of human cancers. It has been recently suggested that GSK3ßmay play an essential role in regulating global protein turnover. Here, we investigate if the GSK3ß phosphorylation site-containing degradation domain of ß-catenin is sufficient to destabilize heterologous proteins. METHODS AND RESULTS: We engineer chimeric proteins by fusing ß-catenin degradation domain at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP). In both transient and stable expression experiments, the chimeric GFP proteins exhibit a significantly decreased stability, which can be effectively antagonized by lithium and Wnt1. An activating mutation in the destruction domain significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB-216763 effectively increases the GFP signal of the fusion protein. Conversely, the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a decrease in GFP signal of the fusion proteins, while these small molecules have no significant effects on the mutant destruction domain-GFP fusion protein. CONCLUSION: Our findings strongly suggest that the ß-catenin degradation domain may be sufficient to destabilize heterologous proteins in Wnt signaling-dependent manner. It is conceivable that the chimeric GFP proteins may be used as a functional reporter to measure the dynamic status of ß-catenin signaling, and to identify potential anticancer drugs that target ß-catenin signaling.

The E-F hand calcium-binding protein S100A4 regulates the proliferation, survival and differentiation potential of human osteosarcoma cells.

BACKGROUND/AIMS: Osteosarcoma (OS) is the most common primary bone malignancy in children and young adults. Molecular mechanisms underlying the pathogenesis of OS remain to be fully understood. Several members of the E-F hand calcium-binding S100 protein family are differentially expressed in human cancers. We previously showed that S100A6 is highly expressed in OS tumors. In this study, we investigated the role of S100A4 in regulating OS proliferation and osteogenic differentiation. METHODS/RESULTS: Endogenous S100 expression was examined by semi-quantitative PCR in human OS lines. Adenoviral vector-mediated overexpression and RNAi knockdown of S100A4 were used to assess S100A4's effects on cell proliferation, migration and invasion and osteogenic differentiation. Apoptosis was assessed by using anti-caspase-3 immunostaining and flow cytometry with annexin V staining. Early osteogenic marker alkaline phosphatase (ALP) and late markers osteocalcin (OCN) and osteopontin (OPN) were assessed to determine the status of osteogenic differentiation. We found that S100A4 was elevated in metastatic MG63.2 cells. S100A4 knockdown inhibited cell proliferation, prolonged cell doubling time, and induced significant apoptosis. Silencing S100A4 expression in OS cells delayed cell wounding closure and diminished the numbers of migrated OS cells in transwell invasion assay. Furthermore, silencing S100A4 expression stimulated ALP activity, as well as late markers OPN and OCN, in both OS cells and mesenchymal stem cells. CONCLUSION: Our results strongly suggest that S100A4 may promote OS tumor growth by regulating the cell cycle, reducing apoptosis, and inhibiting osteogenic differentiation. Thus, S100A4 may serve as a marker for tumorigenic potential, as well as a therapeutic target.

Modulation of ß-catenin signaling by the inhibitors of MAP kinase, tyrosine kinase, and PI3-kinase pathways.

Aberrant activation of ß-catenin signaling plays an important role in human tumorigenesis. However, molecular mechanisms behind the ß-catenin signaling deregulation are mostly unknown because genetic alterations in this pathway only account for a small fraction of tumors. Here, we investigator if other major pathways can regulate ß-catenin signaling activity. By employing a panel of chemical activators and/or inhibitors of several cellular signaling pathways, we assess these modulators' effects on luciferase reporter driven by ß-catenin/TCF4-responsive elements. We find that lithium-stimulated ß-catenin activity is synergistically enhanced by protein kinase C activator PMA. However, ß-catenin-regulated transcriptional (CRT) activity is significantly inhibited by casein kinase II inhibitor DRB, MEK inhibitor PD98059, G-proteins and their receptor uncoupling agent suramin, protein tyrosine kinase inhibitor genistein, and PI-3 kinase inhibitor wortmannin, suggesting that these cellular pathways may participate in regulating ß-catenin signaling. Interestingly, the Ca⁺⁺/calmodulin kinase II inhibitor HDBA is shown to activate ß-catenin activity at low doses. Furthermore, Wnt3A-stimulated and constitutively activated CRT activities, as well as the intracellular accumulation of ß-catenin protein in human colon cancer cells, are effectively suppressed by PD98059, genistein, and wortmannin. We further demonstrate that EGF can activate TCF4/ß-catenin activity and induce the tyrosine phosphorylation of ß-catenin protein. Thus, our results should provide important insights into the molecular mechanisms underlying Wnt/ß-catenin activation. This knowledge should facilitate our efforts to develop efficacious and novel therapeutics by targeting these pathways.

[Myocardial proliferation/regeneration in rats with experimental acute myocardial infarction].

OBJECTIVE: To investigate the myocardial proliferation/regeneration capacities at different time points and at different parts of the heart post acute myocardial infarction (AMI) in rats. METHODS: A total of 64 adult Sprague-Dawley (SD) rats were randomly divided into AMI group (left anterior descending coronary ligation, n = 44) and sham-operated group (n = 20). Rats were sacrificed on day 3, 5, 7, 14 and 60 respectively post operation (n = 5-9 at each time point) and ventricular tissues were harvested. 5-Bromo-2-deoxyUridine (Brdu, 50 mg/kg) was injected intraperitoneally at 12 and 24 hours before sacrifice. Morphological and pathological changes of the myocardium were observed after HE staining. Brdu-positive and c-kit and Brdu double-positive cardiomyocytes were analyzed post immunohistochemistry and immunofluorescence staining. Striated structure of new cells was detected by PTAH staining. Alpha-sarcomeric actin antibody was used to identify new cardiomyocytes. RESULT: Brdu-positive cardiomyocytes at border zone and non-ischemic zone were significantly increased at 5 days post AMI and peaked at 7th day post operation (Border zone, AMI: 1.26% ± 0.15% vs.Sham: 0.22% ± 0.06%, P < 0.01; right ventricle, AMI: 0.75% ± 0.12% vs.Sham: 0.18% ± 0.07%, P < 0.01). There was no significant difference between the two groups on the 60th post-operation day. Brdu-positive cells were 1.7-fold higher in infarct border zone than in the right ventricular area of AMI rats on the 7th post operation day (1.26% ± 0.15%, vs.0.75% ± 0.12%, P < 0.01) and was 1.4-fold higher on the 14th post operation day (0.77% ± 0.09%, vs.0.54% ± 0.11%, P < 0.01). PTAH staining evidenced myocardial striated structure inside the new cells. Immunofluorescent assay showed that parts of Brdu positive cells were myocardial actin positive, and the c-kit and Brdu double-positive myocardial cells were also observed. Most nuclei of tehse new cardiomyocytes were small and round-shaped. CONCLUSIONS: Myocardial proliferation/regeneration increased significantly after AMI in rats, especially around the infarct border zone. The myocardial proliferation/regeneration was time-dependent. Parts of the new cardiomyocytes had some characteristics of cardiac stem cells. This study suggests that myocardial proliferation/regeneration may be activated after acute myocardial injury.

Fast autofocus method for piezoelectric microscopy system for high interaction scenes.

Piezoelectric objective driver positioners are increasingly used in the field of microscopy. They have the advantages of high dynamic and fast response. This paper presents a fast autofocus algorithm for highly interactive microscope system. First, the Tenengrad gradient of the down-sampled image is used to calculate the image sharpness, and Brent search method is adopted to quickly converge to the correct focal length. At the same time, the input shaping method is used to eliminate the displacement vibration of the piezoelectric objective lens driver and further accelerate the image acquisition speed. Experimental results show that the proposed scheme can improve the speed of the automatic focusing task of the piezoelectric objective driver and improve the real-time focus of the automatic microscopic system. HIGHLIGHTS: A high real-time autofocus strategy. A vibration control method suitable for a piezoelectric objective driver.

A dynamic parallel image acquisition method for slide scanning process.

Automated microscope systems have played an important role in the screening of numerous diseases. However, it is a very time-consuming process to continuously acquire images under the high magnification objective lens. This paper proposes a dynamic parallel image acquisition method, which can greatly improve image acquisition speed. Due to the relative motion between the x-y stage and the camera, some of the captured images have motion blur To this end, we also designed a motor variable speed motion curve to ensure the quality of the collected images. The experimental results show that the traditional image scanning mode needs 47.3 ms to obtain continuous microscopic images, while the dynamic parallel image acquisition method only needs 25.4 ms, which improves the acquisition speed without affecting the clarity of the acquired images.

Modeling of Rapid Response Characteristics of Piezoelectric Actuators for Ultra-Precision Machining.

Piezoelectric actuators are characterized by high positioning accuracy, high stiffness and a fast response and are widely used in ultra-precision machining technologies such as fast tool servo technology and ultrasonic machining. The rapid response characteristics of piezoelectric actuators often determine the overall quality of machining. However, there has been little research on the fast response characteristics of piezoelectric actuators, and this knowledge gap will lead to low precision and poor quality of the final machining. The fast response characteristics of a piezoelectric actuator were studied in this work. Firstly, the piezoelectric actuator was divided into a no-load state and a load state according to the working state. A fast response analysis and output characteristic analysis were carried out, the corresponding dynamic model was established, and then the model was simulated. Finally, an experimental system was established to verify the dynamic model of the piezoelectric actuator's fast response by conducting an experiment in which the piezoelectric actuator bounces a steel ball. The experimental results verify the correctness of the model and show that the greater the cross-sectional area and height of the piezoelectric actuator, the higher the bouncing height of the ball, and the better the dynamic performance of the piezoelectric actuator. It is believed that this study has guiding significance for the application of the dynamic characteristics of piezoelectric actuators in the machining field.

RDDL: A systematic ensemble pipeline tool that streamlines balancing training schemes to reduce the effects of data imbalance in rare-disease-related deep-learning applications.

Identifying lowly prevalent diseases, or rare diseases, in their early stages is key to disease treatment in the medical field. Deep learning techniques now provide promising tools for this purpose. Nevertheless, the low prevalence of rare diseases entangles the proper application of deep networks for disease identification due to the severe class-imbalance issue. In the past decades, some balancing methods have been studied to handle the data-imbalance issue. The bad news is that it is verified that none of these methods guarantees superior performance to others. This performance variation causes the need to formulate a systematic pipeline with a comprehensive software tool for enhancing deep-learning applications in rare disease identification. We reviewed the existing balancing schemes and summarized a systematic deep ensemble pipeline with a constructed tool called RDDL for handling the data imbalance issue. Through two real case studies, we showed that rare disease identification could be boosted with this systematic RDDL pipeline tool by lessening the data imbalance problem during model training. The RDDL pipeline tool is available at https://github.com/cobisLab/RDDL/.

SSRTool: A web tool for evaluating RNA secondary structure predictions based on species-specific functional interpretability.

RNA secondary structures can carry out essential cellular functions alone or interact with one another to form the hierarchical tertiary structures. Experimental structure identification approa ches can show the in vitro structures of RNA molecules. However, they usually have limits in the resolution and are costly. In silico structure prediction tools are thus primarily relied on for pre-experiment analysis. Various structure prediction models have been developed over the decades. Since these tools are usually used before knowing the actual RNA structures, evaluating and ranking the pile of secondary structure predictions of a given sequence is essential in computational analysis. In this research, we implemented a web service called SSRTool (RNA Secondary Structure prediction Ranking Tool) to assist in the ranking and evaluation of the generated predicted structures of a given sequence. Based on the computed species-specific interpretability significance in four common RNA structure-function aspects, SSRTool provides three functions along with visualization interfaces: (1) Rank user-generated predictions. (2) Provide an automated streamline of structure prediction and ranking for a given sequence. (3) Infer the functional aspects of a given structure. We demonstrated the applicability of SSRTool via real case studies and reported the similar trends between computed species-specific rankings and the corresponding prediction F1 values. The SSRTool web service is available online at https://cobisHSS0.im.nuk.edu.tw/SSRTool/, http://cosbi3.ee.ncku.edu.tw/SSRTool/, or the redirecting site https://github.com/cobisLab/SSRTool/.

Biofunctionalization of 3D Printed Porous Tantalum Using a Vancomycin-Carboxymethyl Chitosan Composite Coating to Improve Osteogenesis and Antibiofilm Properties.

3D-printed porous tantalum scaffold has been increasingly used in arthroplasty due to its bone-matching elastic modulus and good osteoinductive ability. However, the lack of antibacterial ability makes it difficult for tantalum to prevent the occurrence and development of periprosthetic joint infection. The difficulty and high cost of curing periprosthetic joint infection (PJI) and revision surgery limit the further clinical application of tantalum. Therefore, we fabricated vancomycin-loaded porous tantalum scaffolds by combining the chemical grafting of (3-aminopropyl)triethoxysilane (APTES) and the electrostatic assembly of carboxymethyl chitosan and vancomycin for the first time. Our in vitro experiments show that the scaffold achieves rapid killing of initially adherent bacteria and effectively prevents biofilm formation. In addition, our modification preserves the original excellent structure and biocompatibility of porous tantalum and promotes the generation of mineralized matrix and osteogenesis-related gene expression by mesenchymal stem cells on the surface of scaffolds. Through a rat subcutaneous infection model, the composite bioscaffold shows efficient bacterial clearance and inflammation control in soft tissue and creates an immune microenvironment suitable for tissue repair at an early stage. Combined with the economic friendliness and practicality of its preparation, this scaffold has great clinical application potential in the treatment of periprosthetic joint infection.

[Retracted] Small interfering RNA­induced silencing of galectin­3 inhibits the malignant phenotypes of osteosarcoma in vitro.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration assay data shown in Figs. 4B and 5B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 6316­6322, 2015; DOI: 10.3892/mmr.2015.4165].

A Portable Wireless Urine Detection System With Power-Efficient Electrochemical Readout ASIC and ABTS-CNT Biosensor for UACR Detection.

This work presents a portable wireless urine detection system which consists of an electrochemical readout application specific integrated circuit (ASIC) and a biosensor composed of 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and carbon nanotube (ABTS-CNT) for the detection of urine albumin-to-creatinine ratio (UACR). The ASIC includes a potentiostat, a digital circuitry and a power management circuit which can perform electrochemistry techniques with a dual-channel screen-printing carbon electrode (SPCE). Electrochemical experiments on the proposed biosensor (SPCE|ABTS-CNT|Nafion) have revealed promising sensing characteristics for creatinine and human serum albumin detection. Practical urine tests has demonstrated the capability of the proposed urine detection system for UACR detection with both the power-efficient readout ASIC and the ABTS-CNT biosensor. A user-friendly prototype has also been designed which can be useful for either personal health administrationor homecare.

Correction: Adenovirus-Mediated Efficient Gene Transfer into Cultured Three-Dimensional Organoids.

[This corrects the article DOI: 10.1371/journal.pone.0093608.].

Assessment of the Learning Curve of Supercapsular Percutaneously Assisted Total Hip Arthroplasty in an Asian Population.

The supercapsular percutaneously assisted total hip (SuperPATH) approach is a microinvasive approach that was developed to minimize surgical disruption of soft tissue during routine total hip arthroplasty (THA). This study was aimed at assessing early outcomes and learning curves of the SuperPATH approach in one Chinese hospital's experience. Early outcomes of the first consecutive 78 SuperPATH cases (80 hips) performed by the same surgeon were evaluated. The patients were divided into 4 groups according to the surgical order. The incision, intraoperative blood loss, hospital stay, Harris hip score, and complication occurrence in each group were evaluated. Learning curves were assessed using operative time and intraoperative blood loss as surrogates. The operation time and intraoperative blood loss of groups A and B were more than those of groups C and D, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference between the two groups (group A vs. group B, P = 0.426; group A vs. group B, P = 0.426). There was no statistically significant difference in terms of incision length and hospital stay, and Harris hip score at the last follow-up was increased with statistically significant difference when compared with that preoperatively among the 4 groups. One case of periprosthetic fracture occurred in group A. No other complication, such as joint dislocation, sciatic nerve injury, prosthesis loosening, periprosthetic infection, and deep vein thromboembolism, occurred in the 4 groups. In summary, for surgeons who are familiar with the standard posterolateral approach, they could achieve more familiarity with SuperPATH after 40 cases of surgery.