SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.

Integration of multiplatform metabolomics and multivariate analysis for geographical origin discrimination of Panax ginseng.

As the health food industry grows, the market for ginseng also expands globally. Korean ginseng (Panax ginseng C. A. Meyer) is cultivated in East Asian countries such as Korea, China, and Japan. The metabolic profile of plants can vary depending on the cultivation environment. As such, in this study, we aimed to compare the differences in the metabolic profiles of P. ginseng cultivated in Korea, China, and Japan, and to construct a library of these metabolite data. Using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), we profiled 62 types of secondary metabolites, ginsenosides, using optimized analysis conditions to separate peaks with a high-resolution for about 30 min. In addition, we selected ginsenosides showing differences between their origins were selected among the possible origins in the S-line plot of orthogonal partial least squares discriminant analysis (OPLS-DA), which we quantitatively analyzed using UPLC-tandem mass spectrometry (UPLC-MS/MS). The contents of ginsenosides Ra1, Ra2, Ra3, and Rk1 were high in Korean P. ginseng; the contents of ginsenosides Rb1, Rb2, and Rc were high in Japanese P. ginseng; and the contents of the ginsenoside Ro was high in Chinese P. ginseng. We also analyzed the primary metabolite contents using nuclear magnetic resonance (NMR) spectroscopy and gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). Japanese P. ginseng showed a high sucrose content and Korean P. ginseng showed high contents of most amino acids and organic acids. In the PLS-DA results of multivariate statistical analysis using the data obtained from each analysis instrument, we observed a clear clustering among the three origins. Although a genetically identical species, the metabolic profile substantially differs depending on the cultivation environment. Because ginsenoside, having many biological activities, showed origin-dependent origins, when P. ginseng is used for medicinal purposes, its content by origin should be considered. After disclosing the profiling results of these metabolites, we expect that they will be used in future ginseng research.

Impact of Iterative Deuterium Annealing in Long-Channel MOSFET Performance.

In contrast to conventional forming gas annealing (FGA), high-pressure deuterium annealing (HPD) shows a superior passivation of dangling bonds on the Si/SiO2 interface. However, research detailing the process optimization for HPD has been modest. In this context, this paper demonstrates the iterative impact of HPD for the better fabrication of semiconductor devices. Long-channel gate-enclosed FETs are fabricated as a test vehicle. After each cycle of the annealing, device parameters are extracted and compared depending on the number of the HPD. Based on the results, an HPD condition that maximizes on-state current (ION) but minimizes off-state current (IOFF) can be provided.

Which orally administered antithrombotic agent is most effective for preventing venous thromboembolism after total knee arthroplasty? A propensity score-matching analysis.

PURPOSE: Even today, total knee arthroplasty (TKA) is associated with venous thromboembolism (VTE). The purpose of our study is to report the incidence of postoperative VTE and to compare the efficacy of commonly used orally administered antithrombotic agents. MATERIALS AND METHODS: Seven hundred ad ninety-nine patients who underwent primary TKA were retrospectively reviewed. The patients were prescribed one of three antithrombotic agents: aspirin (n = 168), rivaroxaban (n = 117), or apixaban (n = 514). Before surgery, patient demographics and risk factors were matched via propensity scoring. After surgery, all three groups took the agent for 7 days and underwent ultrasonography to check for VTE. RESULTS: The overall incidence of postoperative VTE was 15.4% (123/799). Only one patient developed symptomatic VTE. Female sex and staged bilateral TKA were risk factors for postoperative VTE. The postoperative VTE rates in the aspirin, rivaroxaban, and apixaban groups were 16.2%, 6.0%, and 17.1%, respectively, significantly lower in the rivaroxaban group (p <  0.02). The majority of VTEs in all three groups were calf-vein thromboses. CONCLUSIONS: All agents showed enough efficacy as antithrombotic agents. Considering that aspirin is inexpensive, aspirin is a cost-effective option for preventing postoperative VTE.

Mitigating Effects of Liriope platyphylla on Nicotine-Induced Behavioral Sensitization and Quality Control of Compounds.

In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, back to normal levels, and increases the expression of dopamine transporter (DAT) protein, which is reduced by nicotine, back to normal levels in PC12 cells. In this study, rats received nicotine (0.4 mg/kg, subcutaneously) only for seven days and then received extract of L. platyphylla (200 or 400 mg/kg, oral) 1 h prior to nicotine administration for an additional seven days. The extract of L. platyphylla reduced locomotor activity compared to the nicotine control group in rats. The extract of L. platyphylla significantly attenuated the repeated nicotine-induced DAT protein expression in the nucleus accumbens (NAc), but there was no effect on increased TH protein expression in the dorsal striatum. These findings suggest that L. platyphylla extract has a mitigating effect on nicotine-induced behavioral sensitization by modulating DAT protein expression in the NAc. For quality control of L. plathyphylla, spicatoside A and D, which are saponin compounds, were quantified in the L. platyphylla extract. The amounts of spicatoside A and D in L. platyphylla extract obtained from ultra-high-performance liquid chromatography with tandem mass spectrometry were 0.148 and 0.272 mg/g, respectively. The identification of these compounds in L. platyphylla, which can be used for quality control, provides important information for the development of drugs to treat nicotine dependence.

A Comparative Study on Processed Panax ginseng Products Using HR-MAS NMR-Based Metabolomics.

Panax ginseng is processed to diversify efficacy. Four processed ginsengs containing white ginseng (WG), tae-geuk ginseng (TG), red ginseng (RG), and black ginseng (BG) were analyzed using nuclear magnetic resonance (NMR) spectroscopy for screening overall primary metabolites. There were significant differences in the sugar content among these four processed ginseng products. WG had a high sucrose content, TG had a high maltose content, and BG had high fructose and glucose content. In the multivariate analyses of NMR spectra, the PCA score plot showed significant discrimination between the four processed ginsengs. For effective clustering, orthogonal partial least squares discriminant analyses (OPLS-DA) with a 1:1 comparison were conducted and all OPLS models were validated using the permutation test, the root mean square error of estimation (RMSEE), and the root mean square error of prediction (RMSEP). All OPLS-DA score plots showed clear separations of processed ginseng products, and sugars such as sucrose and fructose mainly contributed to these separations.

Transfusion after total knee arthroplasty can be predicted using the machine learning algorithm.

PURPOSE: A blood transfusion after total knee arthroplasty (TKA) is associated with an increase in complication and infection rates. However, no studies have been conducted to predict transfusion after TKA using a machine learning algorithm. The purpose of this study was to identify informative preoperative variables to create a machine learning model, and to provide a web-based transfusion risk-assessment system for clinical use. METHODS: This study retrospectively reviewed 1686 patients who underwent TKA at our institution. Data for 43 preoperative variables, including medication history, laboratory values, and demographic characteristics, were collected. Variable selection was conducted using the recursive feature elimination algorithm. The transfusion group was defined as patients with haemoglobin (Hb) < 7 g/dL after TKA. A predictive model was developed using the gradient boosting machine, and the performance of the model was assessed by the area under the receiver operating characteristic curve (AUC). Data sets from an independent institution were tested with the model for external validation. RESULTS: Of the 1686 patients who underwent TKA, 108 (6.4%) were categorized into the transfusion group. Six preoperative variables were selected, including preoperative Hb, platelet count, type of surgery, tranexamic acid, age, and body weight. The predictive model demonstrated good predictive performance using the six variables [AUC 0.842; 95% confidence interval (CI) 0.820-0.856]. Performance was also good according to the external validation using 400 data from an independent institution (AUC 0.880; 95% CI 0.844-0.910). This web-based blood transfusion risk-assessment system can be accessed at http://safetka.net. CONCLUSIONS: A web-based predictive model for transfusion after TKA using a machine learning algorithm was developed using six preoperative variables. The model is simple, has been validated, showed good performance, and can be used before TKA to predict the risk of transfusion and guide appropriate precautions for high-risk patients. LEVEL OF EVIDENCE: Diagnostic level II.

Synthesis of ultrathin polymer insulating layers by initiated chemical vapour deposition for low-power soft electronics.

Insulating layers based on oxides and nitrides provide high capacitance, low leakage, high breakdown field and resistance to electrical stresses when used in electronic devices based on rigid substrates. However, their typically high process temperatures and brittleness make it difficult to achieve similar performance in flexible or organic electronics. Here, we show that poly(1,3,5-trimethyl-1,3,5-trivinyl cyclotrisiloxane) (pV3D3) prepared via a one-step, solvent-free technique called initiated chemical vapour deposition (iCVD) is a versatile polymeric insulating layer that meets a wide range of requirements for next-generation electronic devices. Highly uniform and pure ultrathin films of pV3D3 with excellent insulating properties, a large energy gap (>8 eV), tunnelling-limited leakage characteristics and resistance to a tensile strain of up to 4% are demonstrated. The low process temperature, surface-growth character, and solvent-free nature of the iCVD process enable pV3D3 to be grown conformally on plastic substrates to yield flexible field-effect transistors as well as on a variety of channel layers, including organics, oxides, and graphene.

Locked tension band wiring using ring pins for patellar fractures: a method of minimising implant migration.

BACKGROUND: A modified K-wire attached with ring (ring pin) was used to treat a displaced patellar fracture, and the ring pin was locked with tension band wiring. The purpose of this study was to evaluate the surgical outcome of this method with respect to its procedural safety. METHODS: The authors retrospectively reviewed 36 patients treated for a displaced patellar fracture and assessed bone union, fixation failure, postoperative pain, range of motion, and incidence of hardware removal. Clinical outcome was evaluated using the Böstman scoring system. The mean follow-up period was 27 (range 13-47) months. RESULTS: Bony union was achieved in all patients. No fixation failure and pin migration were detected. Hardware was removed in three cases (8.3 %). Reasons for removal were pain in one case and vague discomfort in two cases. The average Böstman scores at 12 months postoperatively were 29.6, with 34 (94.4 %) patients graded as excellent. The average active flexion of the knee joint was 130.4° (range 125°-150°), with an average flexion contracture of 3° (range 0°-10°). CONCLUSIONS: This implant could facilitate satisfactory fixation, restore the integrity of the extensor mechanism, and reduce the possibility of implant migration and implant-related discomfort.

Rectus femoris transfer in cerebral palsy patients with stiff knee gait.

BACKGROUND: Although several studies have reported on the outcomes of rectus femoris transfer (RFT), few have investigated the multiple factors that could affect the results. Therefore, we evaluated the outcomes of RFT and analyzed factors that influence improvement and annual change in knee motion after surgery in patients with cerebral palsy (CP). METHODS: We reviewed ambulatory patients with CP who were followed up after they had undergone RFT as part of a single-event multilevel surgery (SEMLS) and who had undergone preoperative and postoperative three-dimensional (3D) gait analysis between January 1995 and December 2012. Relevant kinematic values, including peak knee flexion, knee range of motion, and timing of peak knee flexion in the swing phase and gait deviation index (GDI) score, were the outcome measures. Improvements in rate of angle and GDI score were adjusted by multiple factors such as sex, Gross Motor Function Classification System (GMFCS) level, anatomic type of CP, and concomitant surgeries as the fixed effects, and follow-up duration, laterality, and each subject as the random effects, all of which was performed using a linear mixed model. RESULTS: A total of 290 patients (487 limbs) and 612 3D gait analysis (2-4 per patient) results were finally included in this study. At 2 years after RFT, estimated mean peak knee flexion (1.2°, p=0.005), estimated mean knee range of motion (10.7°, p<0.001), and estimated mean GDI score (7.3, p<0.001) increased significantly. Peak knee flexion in the swing phase occurred 5.4% earlier after surgery compared with that at baseline (p<0.001). In serial postoperative gait analyses, peak knee flexion in the swing phase occurred 0.8% earlier per year in patients with GMFCS level I or II (p=0.021). CONCLUSIONS: RFT as part of a SEMLS was effective in treating stiff knee gait. In serial postoperative gait analyses, patients with GMFCS level I or II showed better prognosis than those with level III with regard to timing of peak knee flexion in the swing phase. LEVEL OF EVIDENCE: Prognostic level IV.

Functionalized graphene as an ultrathin seed layer for the atomic layer deposition of conformal high-k dielectrics on graphene.

Ultrathin functionalized graphene (FG) is demonstrated to work as an effective seed layer for the atomic layer deposition (ALD) of high-k dielectrics on graphene that is synthesized via chemical vapor deposition (CVD). The FG layer is prepared using a low-density oxygen plasma treatment on CVD graphene and is characterized using Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). While the ALD deposition on graphene results in a patchy and rough dielectric deposition, the abundant oxygen species provided by the FG seed layer enable conformal and pinhole-free dielectric film deposition over the entire area of the graphene channel. The metal-insulator-graphene (MIG) capacitors fabricated with the FG-seeded Al2O3 exhibit superior scaling capabilities with low leakage currents when compared with the co-processed capacitors with Al seed layers.

Direct measurement of adhesion energy of monolayer graphene as-grown on copper and its application to renewable transfer process.

Direct measurement of the adhesion energy of monolayer graphene as-grown on metal substrates is important to better understand its bonding mechanism and control the mechanical release of the graphene from the substrates, but it has not been reported yet. We report the adhesion energy of large-area monolayer graphene synthesized on copper measured by double cantilever beam fracture mechanics testing. The adhesion energy of 0.72 ± 0.07 J m(-2) was found. Knowing the directly measured value, we further demonstrate the etching-free renewable transfer process of monolayer graphene that utilizes the repetition of the mechanical delamination followed by the regrowth of monolayer graphene on a copper substrate.

Inhibition of L-type amino acid transporter modulates the expression of cell cycle regulatory factors in KB oral cancer cells.

The purpose of this study was to examine the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), an inhibitor of L-type amino acid transporters, on the cell growth suppression in KB human oral cancer cells and to study the roles of cell cycle regulatory factors in the BCH-induced growth inhibition. The effect of BCH on cell growth suppression and the influence of BCH to cell cycle regulatory factors in KB cell growth inhibition were examined using cell cycle analysis, immunoblotting and immunoprecipitation. The BCH treatment induced cell cycle arrest at G1 phase in KB cells. The expression of cyclin D3 was remarkably decreased by BCH treatment. The BCH inhibited the expression of cyclin-dependent protein kinase 6 (CDK6) in a time-dependent manner. In addition, the expression of CDK inhibitor p27 was increased by BCH treatment in KB cells, but not CDK inhibitors p21 and p15. These results suggest that, in KB cells, the inhibition of LAT1 by BCH causes cell cycle arrest at G1 phase by inhibiting cyclin D3-CDK6 complex whereas increasing expression of a CDK inhibitor p27.