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The translucent white-coloured, Gram-stain-negative, aerobic, non-motile, fusiform-shaped bacterium (designated strain SY72T) was isolated from waste-activated sludge. Optimal growth occurred at 30–37 °C and pH 6.0–7.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the novel isolate belonged to the family Rhodobacteraceae of the class Alphaproteobacteria . Strain SY72T is closely related to Tabrizicola aquatica KCTC 23724T (97.8 % 16S rRNA gene sequence similarity) and Pseudorhodobacter aquaticus DC2N1-10T (96.4 %), respectively. DNA–DNA relatedness between strain SY72T and the closest phylogenetically related strain, Tabrizicola aquatica KCTC 23724T, was 18.0±0.7 %. In strain SY72T, the predominant respiratory quinone was ubiquinone Q-10, and the cellular fatty acids consisted mainly of C18 : 1ω7c and C18 : 1ω7c-11 methyl. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. Photoautotrophic and photoheterotrophic growth did not occur in strain SY72T. Furthermore, strain SY72T did not produce photosynthetic pigments or contain the photosynthetic genes pufL and pufM, by which it differed from the phototrophic species of the family Rhodobacteraceae . On the basis of distinct phenotypic and phylogenetic properties, strain SY72T represents a novel species of the genus Tabrizicola , for which the name Tabrizicola fusiformis sp. nov. is proposed. The type strain is SY72T (=KCTC 62105T=NBRC 113021T).

A digital fractional-N phase-locked loop (PLL) is presented. It achieves 137- and 142-fs rms jitter integrating from 10 kHz to 10 MHz and from 1 kHz to 10 MHz, respectively. With a frequency multiplication ratio of 207.0019231 [digitally controlled oscillator (DCO) frequency is 50 kHz away from an integer multiple of the 26-MHz reference clock], a −78.6-dBc fractional spur is achieved for an output clock that runs at half of the DCO frequency. Time-to-digital converter (TDC) chopping technique, TDC fine conversion through successive approximation register analog-to-digital converters (SARADCs), and TDC nonlinearity calibration improve integrated phase noise and fractional spurs. This design meets the performance requirement of the 256-QAM $4 \times 4$ MIMO LTE standard in 5-GHz ISM band and also the 5G cellular 64-QAM standard in 28-GHz band. This work, implemented in a 14-nm fin-shaped field effect transistor (FinFET) CMOS process, is integrated to a cellular RF integrated circuit supporting advanced carrier aggregation operation. This PLL draws 13.4 mW and occupies 0.257 mm2.

Much progress has been made since plasma was discovered in the early 1900s. The first form of plasma was thermal type, which was limited for medical use due to potential thermal damage on living cells. In the late 1900s, with the development of a nonthermal atmospheric plasma called cold plasma, profound clinical research began and ‘plasma medicine’ became a new area in the academic field. Plasma began to be used mainly for environmental problems, such as water purification and wastewater treatment, and subsequent research on plasma and liquid interaction led to the birth of ‘plasma-activated liquid’ (PAL). PAL is currently used in the fields of environment, food, agriculture, nanoparticle synthesis, analytical chemistry, and sterilization. In the medical field, PAL usage can be expanded for accessing places where direct application of plasma is difficult. In this review, recent studies with PAL will be introduced to inform researchers of the application plan and possibility of PAL in the medical field.

This study used a more detailed dataset approach to address the limitations of existing building energy prediction methods and to predict building energy demand more accurately. The EnergyPlus dynamic simulation program closely modeled building envelope performance, zone division, and heating, ventilation, and air conditioning systems. Building energy simulation used actual weather data and generated occupancy data. The occupancy, lighting, and equipment schedules for each zone were generated in 5-min intervals using the Lawrence Berkeley National Laboratory occupancy simulator. Summer electric power consumption based on Internet of Things information from the testbed building validated the model. When applying generated occupancy, lighting, and equipment schedules, the mean bias error of simulation similarly improved to 4.73%, and the coefficient of variation of the root-mean-squared error (Cv(RMSE]) improved to 12.26%. Subsequently, a demand prediction model was constructed as a sequence-to-sequence (seq2seq) model using long short-term memory (LSTM) cells in recurrent neural network (RNN) algorithms, then its accuracy was evaluated. In the seq2seq model, the learning performance based on the EnergyPlus data exhibited an RMSE of 4.48% and a weighted average percentage error of 3.07%. As a result of applying prediction methods while changing climate scenarios, prediction performance also satisfied statistically significant levels. The occupancy information and solar radiation were determined to exert the greatest influence on the building energy demand prediction.

Background Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the parallelism of screws remains controversial. Materials and Methods MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before June 2, 2020, that compared the use of parallel and non-parallel screw fixation for the treatment of FNF. The pooled analysis was designed to identify differences between the two groups and focused on postoperative complications, including fracture nonunion and osteonecrosis of the femoral head (ONFH). Results Over four studies, we enrolled 445 patients, including 195 patients with fixed FNF with parallel trajectory screws and 250 patients with fixed FNF with non-parallel screws. The pooled analysis showed no difference in the nonunion rates (odds ratio (OR) = 0.91; 95 % confidence interval (CI), 0.24–3.44; P = 0.89) and no significant difference in the incidence of ONFH between parallel and non-parallel screw fixation (OR = 0.74; 95 % CI: 0.21–2.63; P = 0.64). Conclusions The results of this meta-analysis reveal that screw parallelism in multiple cannulated screw fixation of FNF has no relationship with either the fracture nonunion rate or the incidence of postoperative ONFH. Level of evidence III; meta-analysis.

Although many graft materials have been used for augmentation rhinoplasty, an ideal graft has not yet been developed. As the field of tissue engineering has been developing, it has been applied to the reconstruction of many organs, but its application in the rhinoplasty field is still limited. This study evaluated the utility of allogenic chondrocytes with fibrin/hyaluronic acid (HA)–poly(l-lactic-co-glycolic acid) (PLGA) constructs in augmentation rhinoplasty. Chondrocytes from rabbit auricular cartilage were isolated and cultured with fibrin/HA hydrogels and implanted into PLGA scaffolds. After 8 weeks of in vitro culture, the scaffolds were implanted in the nasal dorsum of six rabbits. Eight weeks postoperatively, the implanted sites were evaluated with gross, radiologic, and histologic analysis. In vitro, more than 90% of the seeded chondrocytes in the PLGA scaffolds survived for 2 weeks, and they produced a large amount of extracellular matrix and were well differentiated. The grafts maintained their initial shape for 8 weeks after implantation. Radiological and histological evaluations showed that the structure was well maintained with minimal inflammatory response and appropriate elevation levels. However, the formation of neo-chondrocytes was not observed. PLGA scaffolds seeded with fibrin/HA and allogenic chondrocytes can be a biocompatible augmentation material in rhinoplasty in the future.

Plasma medicine is emerging as a novel therapeutic field. It has been reported that plasma can kill bacteria, promote wound healing and induce apoptosis of tumor cells. However, the effects of plasma on immune cells and immune related skin diseases have not been well studied. In this study, we demonstrated that non-thermal atmospheric plasma (NTP) treatment can inhibit psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced through application of imiquimod for 5 days and NTP was treated on days 3 and 4. On day 5 mice were sacrificed for analysis. NTP treatment in imiquimod-applied mouse skin inhibited increases in epithelial cell thickness compared to imiquimod-applied mouse skin without NTP treatment and suppressed immune cell infiltration in the mouse skins. The expression of cytokines and chemokines and NF-κB activation in the skin were also suppressed by the NTP treatment. In addition, differentiation of Th17 cells, an important cell type for the pathogenesis of psoriasis, was inhibited in the NTP-treated mouse lymph nodes. It was also demonstrated that liquid type plasma (LTP), which is also known as indirect plasma, inhibited Th17 cell differentiation in vitro. Other in vitro experiments showed that LTP inhibits bone marrow-derived dendritic cell (BMDC) activation, and inflammation of HaCaT cells. Interestingly, LTP enhanced PD-L1 expression in BMDC and HaCaT cells, suggesting that NTP may inhibit unwanted over-activation of T cells through increased PD-L1 expression in dendritic cells or epithelial cells. Taken together, these results suggest that NTP can be used to treat CD4+ T cell-mediated autoimmune diseases such as psoriasis.

Background Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. Methods We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness. Subjects performed a brief maximal intensity cycling regimen and a longer less intense cycling regimen at separate visits. Leukocytes were measured by multi-parameter flow cytometry of more than 50 immunophenotypes for each collection sample. Results We found a differential induction of leukocytosis dependent on exercise intensity and duration. Cytotoxic natural killer cells demonstrated the greatest increase (average of 5.6 fold) immediately post-maximal exercise whereas CD15+ granulocytes demonstrated the largest increase at 3 h post-maximal exercise (1.6 fold). The longer, less intense endurance exercise resulted in an attenuated leukocytosis. Induction of leukocytosis did not differ in our limited study of active (n = 10) and sedentary (n = 5) subjects to exercise although we found that in baseline samples, sedentary individuals had elevated percentages of CD45RO+ memory CD4+ T cells and elevated proportions of CD4+ T cells expressing the negative immune regulator programmed death-1 (PD-1). Finally, we identified several leukocytes whose presence correlated with obesity related fitness parameters. Conclusions Our data suggests that leukocytes subsets are differentially mobilized into the peripheral blood and dependent on the intensity and duration of exercise. Pre-existing compositional differences of leukocytes were associated with various fitness parameters. Electronic supplementary material The online version of this article (doi:10.1186/s40425-017-0231-8) contains supplementary material, which is available to authorized users.

Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N2 NTP was verified on rat wound model. Taken together, these results suggest that N2 NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing.

Microalgae have recently attracted tremendous attention as a possible feedstock for biofuel production. In this study, the pyrolysis characteristics and kinetics of Aurantiochytrium sp. KRS101, a kind of heterotrophic oleaginous microalgae, were investigated by means of thermogravimetric analysis and pyrolysis in a micro-tubing reactor. Most biochemical components of the microalgae (carbohydrates, proteins, and lipids) were decomposed between 150 and 600 °C at heating rates of 5–20 °C/min. Derivative thermogravimetry (DTG) curves were deconvoluted to more fully understand the separate decompositions of carbohydrates, proteins, and lipids. Experimental results of pyrolysis in the micro-tubing reactor were consistent with the predictions of the proposed lumped kinetic model, and the kinetic rate constants indicated that the predominant reaction pathway under the investigated pyrolysis conditions was from biomass to bio-oil rather than from biomass to gas.

Background: Femoroacetabular impingement (FAI) can be managed either conservatively or by a surgical correction of the deformity causing impingement. However, there is insufficient evidence to justify an immediate surgical treatment in all symptomatic patients, and the role of a nonoperative treatment is unclear. This study evaluates the role of conservative treatment for FAI. Materials and Methods: 87 patients (102 hips) diagnosed as FAI between January 2011 and May 2012 were included in this retrospective study. All patients underwent an initial 3-month conservative treatment followed by arthroscopic hip surgery if symptoms did not improve. Clinical outcome scores (modified Harris Hip Score, nonarthritic hip score, and Western Ontario and McMaster Universities Arthritis Index) were evaluated at baseline and at the end of followup, and scores were compared between the nonsurgical and surgical groups. Results: The final analysis included 83 patients (55 men, 28 women; 97 hips) because four patients were lost to followup. The average age was 45.1 years and 14 patients had bilateral symptomatic FAI. After an initial conservative treatment averaging 27.5 months (range 24–36 months), 53 hips (54.6%) could perform normal daily activities. The nonsurgical group had significant improvements in all clinical scores at the end of followup (P < 0.001). Forty four hips (45.4%) were unresponsive to conservative treatment and underwent arthroscopic hip surgery with subsequent significant improvements in clinical scores (P < 0.001). At the end of followup, there were no significant differences in clinical scores between the two groups. Conclusion: An initial trial of conservative treatment of sufficient length should be considered for FAI patients before surgical intervention.

We investigated the hydrothermal liquefaction (HTL) of microalgal Aurantiochytrium sp. KRS101 at various reaction temperatures (250∼400 °C) and reaction times (10∼60 min). The product distributions of bio-oil, aqueous-phase, and gaseous products were strongly affected by reaction temperature and time. The highest bio-oil yield of 51.22 wt% was obtained at 400 °C for 10 min. A general quantitative kinetic model was applied to the hydrothermal liquefaction of microalgae, in which aqueous-phase product (AP), bio-oil, and gas were formed from the decomposition of carbohydrates, lipids, and proteins in biomass cells. The rate constants of the model were determined by minimizing the least-squares error between the experimental and calculated data using a MATLAB optimization function. The results show that the model accurately captures the trend in the experimental data. The kinetics rate constants indicate that the formations of bio-oil and aqueous-phase products from decomposition of proteins, lipids, and carbohydrates are the dominant reaction pathways. The kinetic parameters calculated from the model were utilized to explore the parameter space in order to predict liquefaction product yields.

Morphologic features of the proximal femur reminiscent of those seen in patients with femoroacetabular impingement (FAI) have been reported among asymptomatic individuals in Western populations, but whether this is the case in Asian populations is unknown. The purpose of this study was to determine the prevalence of radiographic findings in the proximal femur that are consistent with FAI in asymptomatic Korean volunteers. Two hundred asymptomatic volunteers with no prior hip surgery or childhood hip problems underwent three-view plain radiographs (pelvis AP view, Sugioka view, and 45° Dunn view) of both hips. There were 146 hips from male volunteers and 254 hips from female volunteers in the study. The mean age of all participants was 34.7 years (range, 21–49 years). Cam-type morphologic features were defined as the presence of the following on one or more of the three views: pistol-grip morphologic features, an osseous bump at the femoral head-neck junction, flattening of the femoral head-neck offset, or alpha angle greater than 55°. Pincer-type morphologic features were determined by radiographic signs, including crossover sign, deficient posterior wall sign, or lateral center-edge angle greater than 40°. The prevalence of cam-type morphologic features seen on at least one radiograph was 38% (male, 57%; female, 26%). The prevalence of cam-type features (at least one positive cam-type feature) was 2.0% (male, 6%; female, 0%) on the pelvic AP view, 24% (male, 36%; female, 17%) on the Sugioka view, and 30% (male, 47%; female, 20%) on the 45° Dunn view. The prevalence of pincer-type morphologic features (at least one positive pincer-type feature) was 23% (male, 27%; female, 21%) on the pelvic AP view. The prevalence of FAI-related morphologic features in asymptomatic Asian populations was comparable to the prevalence in Western populations. Considering the high prevalence of radiographic hip findings reminiscent of FAI in asymptomatic Asian populations, it will be important to determine whether FAI-related morphologic features are a cause of hip pain when considering surgery in Asian patients.

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1) respiratory mechanics and the mechanical “cost” of breathing; 2) mechanical interactions of the heart and lungs; and on 3) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.

The present study investigated the minimum 2-year outcomes of hip arthroscopy for femoroacetabular impingement (FAI) and concomitant labral tears in Asian patients.Patients who underwent hip arthroscopy for both FAI and concomitant labral tears between January 2012 and December 2017 were included. Patients with hip osteoarthritis of Tönnis grade ≥2, previous hip surgery, or followed for less than 2 years were excluded. Clinical assessments were performed using the modified Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index, and the rates of achieving threshold values of the minimal clinically important difference and patient acceptable symptomatic state at the latest follow-up. Plain radiographs were acquired pre- and postoperatively for radiologic assessments.A total of 73 patients (90 hips, 58 male, 15 female; mean age 34.4 years) who underwent hip arthroscopy for FAI and concomitant labral tears were enrolled. Forty-three hips (47.8%) had cam-type, 7 (7.8%) had pincer-type, and 40 (44.4%) had mixed-type FAI. The mean follow-up duration was 5.2 years. In cam- and mixed-type FAI hips, the mean α angle significantly decreased from 66.7 ± 8.28° preoperatively to 44.9 ± 3.78° postoperatively (95% confidence interval [CI] 19.6°-22.8°; P.001). The mean modified Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis Index increased from 74.8 ± 13.2 and 75 ± 12.7 preoperatively to 93 ± 8.1 (95% CI 15.4-20.9; P = .001) and 89.4 ± 8.4 postoperatively (95% CI 11.8-17; P = .001), respectively. Seventy-four hips (82.2%) crossed the minimal clinically important difference, and 85 hips (94.4%) had achieved the patient acceptable symptomatic state. There were 2 cases of pudendal nerve palsy and 1 case of sciatic nerve palsy. No additional surgeries were required.Hip arthroscopy can be an effective treatment for FAI and concomitant labral tears in Asian patients as demonstrated in this study, with improved PRO scores and reoperation rates. Longer-term studies with larger cohorts are necessary.Level IV, case series.

We aimed to present the clinical outcomes of multiple drilling and multiple matchstick-like bone allograft for large osteonecrotic lesions of the femoral head as a joint-preserving surgery. Between March 2014 and March 2018, 57 patients (77 hips) who underwent multiple drilling and multiple matchstick-like bone allograft for large lesions (≥ 30%) in osteonecrosis of the femoral head (ONFH) were included. Harris hip scores (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were obtained preoperatively and at the latest follow-up. Plain radiographs were obtained every 3 months. Femoral head collapse ≥ 2 mm was defined as a radiological failure, and conversion to total hip arthroplasty (THA) was regarded as a clinical failure. After exclusion of 5 patients (5 hips) who lost to follow-up, 52 patients (34 men, 18 women; 72 hips) were finally enrolled. The mean follow-up period was 3.4 (range 2–4.5) years. Nineteen hips (28.4%) required conversion to THA at a mean of 21.6 (range 6–42) months postoperatively. In the remaining 53 hips (71.6%) with clinical success, the mean HHS and WOMAC improved from 63 and 31.3 preoperatively to 80.6 and 16.3 at the final follow-up, respectively (p

To provide useful information concerning energy-conserving heating, ventilation, and air-conditioning (HVAC) systems, this study used EnergyPlus to analyze in detail their operational characteristics and energy performance. This study also aimed to understand the features of the systems under consideration by investigating the dry-bulb temperature, relative humidity, and airflow rate at major nodes in each system&rsquo, s schematic. Furthermore, we analyzed the indoor environment created by each HVAC system, as well as examining the cooling energy consumptions and CO2 emissions. The HVAC systems selected for this study are the variable air volume (VAV) commonly used in office buildings (base-case model), constant air volume (CAV), under-floor air distribution (UFAD), and active chilled beam (ACB) with dedicated outdoor air system (DOAS). For the same indoor set-point temperature, the CAV&rsquo, s supply airflow was the highest, and VAV and UFAD were operated by varying the airflow rate according to the change of the space thermal load. ACB with DOAS was analyzed as being able to perform air conditioning only with the supply airflow constantly fixed at a minimum outdoor air volume. The primary cooling energy was increased by about 23.3% by applying CAV, compared to VAV. When using the UFAD and ACB with DOAS, cooling energy was reduced by 11.3% and 23.1% compared with VAV, respectively.

Non-thermal plasma (NTP) has many functional activities such as, sterilization, wound healing and anti-cancer activity. Despite of its wide spread biomedical application, the effect of NTP on immune cells and allergic response has not been well studied. In this study, we determined whether NTP suppresses mast cell activation, which is important for allergic response, and ameliorates an atopic dermatitis (AD)-like skin inflammatory disease in mice. Exposure to NTP-treated medium during mast cell activation inhibited the expression and production of IL-6, TNF-α and suppressed NF-κB activation. We also investigated whether NTP treatment ameliorates house dust mite (HDM)-induced AD-like skin inflammation in mice. NTP treatment inhibited increases in epidermal thickness and recruitment of mast cells and eosinophils, which are important cell types in AD pathogenesis. In addition, Th2 cell differentiation was induced by application of HDM and the differentiation was also inhibited in the draining lymph node of NTP-treated mice. Finally, the expression of AD-related cytokines and chemokines was also decreased in NTP-treated mice. Taken together, these results suggest that NTP might be useful in the treatment of allergic skin diseases, such as AD.

The proposed fully-integrated digital-intensive TRX SoC allows dual-mode protocols of BLE 5.0 and IEEE 802.14.5 with extended-range wireless connectivity and simple ad-hoc mesh networks for the IoTs in smart homes. A 1.04 - 4V with dual-mode supply schemes enables the SoC to be applied for various IoT systems energy-effectively and extends battery lifetime cost-effectively. The TRX employs a low insertion loss CMOS transmit- receive switch, a class-D power amplifier with HD2 calibration, a low-IF RX architecture with ΔΣ ADC-based complex filter, and a low power ADPLL with LMS-based two-point direct frequency modulation. The TRX implemented in a 28nm CMOS process achieves the maximum output power of +10dBm while consuming 45mW at the TX

Injection laryngoplasty is a widely used therapeutic option for drug delivery into vocal folds (VFs). Efficient injectable materials are urgently needed for treating intractable VF disease. Liquid-type non-thermal atmospheric plasma (LTP) has been found to be useful for various biological applications, including in regenerative medicine. We evaluated the effects of LTP on VF regeneration. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by LTP treatment. LTP treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by LPS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit VF scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after LTP injection. Videokymographic analysis showed more improved vibrations in LTP-treated VF mucosa compared to those in non-treated group. In conclusion, LTP treatment enhanced the recruitment and activation of VF-MSCs. Regulated extracellular matrix (ECM) synthesis and eventual functional improvement of scarred VFs were observed upon LTP treatment. The results of this study suggest that LTP injection can enhance wound healing and improve functional remodeling following VF injury.Impact statementVoice disorder has a significant impact on life quality, and one of the major causes of this voice disorder is vocal fold scarring. Therefore, various approaches have been tried to treat for voice disorder. However, no method has satisfied all requirements until now. Plasma medicine, which involves the medical application of plasma, is a rapidly developing field. We have confirmed that liquid-type plasma improved vocal fold scarring by mobilizing and activating vocal fold fibroblast. In conclusion, liquid-type plasma is a potential therapeutic agent for promoting vocal fold scarring through simple injection and it may be an alternative therapeutic agent for the current situation to treat voice disorder.

In this study, to produce adipic acid, mutant strains of Candida tropicalis KCTC 7212 deficient of AOX genes encoding acyl-CoA oxidases which are important in the β-oxidation pathway were constructed. Production of adipic acid in the mutants from the most favorable substrate C12 methyl laurate was significantly increased. The highest level of production of adipic acid was obtained in the C. tropicalis ΔAOX4::AOX5 mutant of 339.8 mg L−1 which was about 5.4-fold higher level compared to the parent strain. The C. tropicalis ΔAOX4::AOX5 mutant was subjected to fed-batch fermentation at optimized conditions of agitation rate of 1000 rpm, pH 5.0 and methyl laurate of 3% (w/v), giving the maximum level of adipic acid of 12.1 g L−1 and production rate of 0.1 g L−1 h−1.

Regulatory T cells (Treg) are targeted for cancer immunotherapy because they suppress antitumor immunity. Although the importance of neuropilin-1 (NRP1) in the stability and function of intratumoral Tregs is well-documented, targeting of NRP1+ Tregs for anticancer immunotherapy has not been well explored. Here, we found that an NRP1 antagonist [Fc(AAG)-TPP11], generated by fusion of the NRP1-specific binding peptide TPP11 with the C-terminus of an effector function–deficient immunoglobulin Fc(AAG) variant, inhibits intratumoral NRP1+ Treg function and stability. Fc(AAG)-TPP11 triggered the internalization of NRP1, reducing its surface expression on Tregs and thereby inhibiting the suppressive function of Tregs. In two murine syngeneic tumor models, Fc(AAG)-TPP11 retarded tumor growth, comparable with a Treg-depleting anti–CTLA-4 antibody, without noticeable toxicity. Fc(AAG)-TPP11 inhibited NRP1-dependent Treg function, inducing unstable intratumoral Tregs, with reduced expression of Foxp3 and enhanced production of IFNγ, which subsequently increased the functionality and frequency of intratumoral CD8+ T cells. We also observed selective expression of NRP1 on Tregs isolated from human tumors, but not from the blood of healthy donors and patients with cancer, as well as ex vivo inhibition of intratumoral NRP1+ Treg function by Fc(AAG)-TPP11. Our results suggest that the NRP1 antagonist Fc(AAG)-TPP11 has therapeutic potential for the inhibition of intratumoral NRP1+ Tregs with limited unfavorable effects on peripheral Tregs.

It has been reported that neutrophil extracellular traps (NETs) impair wound healing in diabetes and that inhibiting NET generation (NETosis) improves wound healing in diabetic mice. Gonadotropin-releasing hormone (GnRH) agonists are associated with a greater risk of diabetes. However, the role of GnRH in diabetic wound healing is unclear. We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing. A mouse model of diabetes was established using five injections with streptozotocin. Mice with blood glucose levels >250 mg/dL were then used in the experiments. GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice. In contrast, GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing. The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients. In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate (PMA)-induced NETosis in mouse and human neutrophils. Furthermore, GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis, which were increased by GnRH treatment. These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds. Thus, inhibition of GnRH might be a novel treatment of diabetic foot ulcers.

The use of nonthermal atmospheric plasma (NTP) in the biomedical field has recently expanded into cell death induction in cancer, infection prevention, inflammation treatment, and wound-healing enhancement. NTP has been demonstrated to enhance skin and muscle regeneration, but its effects on tissue regeneration, following deep tissue or muscle damage, remains underinvestigated. In this study, we determined the effects of NTP on muscle differentiation and the mechanisms of NTP's contribution to differentiation and regeneration. NTP treatment enhanced cell differentiation in primary normal human skeletal muscle myoblast cells and increased the relative expression of mRNA levels of MyoD which is one of the earliest markers of myogenic commitment, and myogenin, which are important transcription factors required for myogenic differentiation. Furthermore, NTP treatment induced increases in the levels of myosin heavy chain, a differentiated muscle-specific protein, and in myotube formation of myoblasts. We observed that signal transducer and activator of transcription 3 (STAT3) activation induced by NTP treatment affects the myogenic differentiation. In addition, STAT3 phosphorylation was also enhanced by NTP treatment in injured animal muscle. These findings indicate that NTP could enhance musculoskeletal differentiation by acting as an external stimulus for myoblast differentiation, suggesting its treatment potential in promoting regeneration of damaged muscle.-Park, J. K., Kim, Y. S., Kang, S. U., Lee, Y. S., Won, H.-R., Kim, C.-H. Nonthermal atmospheric plasma enhances myoblast differentiation by eliciting STAT3 phosphorylation.

Epithelial specific ETS-1 (ESE-1) belongs to the E26 transformation-specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. Despite its clinical significance, the documented effects of ESE-1 on cancer development and progression are contradictory and its underlying biological mechanism of action remains elusive. The objectives of this study are to investigate whether ESE-1 is a tumor suppressor and to identify dietary anti-cancer compound to activate ESE-1 expression in human colon cancer model. ESE-1 knockout and xenograft mouse models were used to examine the effect of ESE-1 in colon tumorigenesis. Stable human colon cancer cell lines were used for in vitro mechanistic studies. ESE-1 knockout in mice increased azoxymethane (AOM)-induced and dextran sulfate sodium (DSS)-promoted formation of aberrant crypt foci (ACF). Conversely, overexpression of ESE-1 suppressed tumorigenicity in a xenograft mouse study, and repressed anchorage-independent growth and migration/invasion in human colon cancer cells. Full length ESE-1 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE-1. Three lysine residues (318 KKK320 ) in the NLS2 determine its nuclear localization. We identified epigallocatechin-3-gallate (EGCG) that acts as a transcriptional activator of ESE-1 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti-cancer compounds for prevention of colon cancer.

Backgroud Outcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH. Methods Eighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint. Results Preoperatively, the necrotic lesion extent was 63.0% (38.4%-96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2). Conclusions Our outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.

Extramedullary (EM) reduction, defined as the medial cortex of the head-neck fragment located outside the medullary canal of the distal shaft fragment, has been introduced to prevent excessive postoperative sliding or failure of the lag screw in pertrochanteric fracture surgeries. Favorable EM reduction results have recently been reported in several clinical and biomechanical studies. Despite these efforts, maintaining the head-neck fragment in an EM position is periodically a difficult and challenging problem. Herein, the technique for reduction and maintenance of the head-neck fragment was introduced in an EM position using a Kirschner wire and partially threaded cannulated screw fixation via screw fixation from EM to the head-neck fragment, which was positioned inferior to the lag screw on the femoral calcar, also called the reduction screw. The authors utilized this reduction screw in 34 pertrochanteric fracture surgeries using a cephalomedullary nail and fracture union was acheive in all cases by a minimum one-year follow-up period without surgical complications.

Background In young active patients with hip dysplasia, choosing between periacetabular osteotomy (PAO) and total hip arthroplasty (THA) is challenging. Materials and methods We systematically searched MEDLINE, Embase, and Cochrane Library for studies published until October 10, 2019, comparing PAO and THA in patients with dysplastic hip. We compared postoperative complications’ incidences, end-stage revisions, and clinical scores. Results Five studies with 431 hips (PAO: 235; THA: 196) were included. The incidence of overall and major complications was not different between groups (PAO: OR 2.14; 95 % CI, 0.58–7.96; p = 0.26; follow-up, 4–7.8 years; THA: OR 2.56; 95 % CI, 0.60–10.98; p = 0.21; follow-up, 4–7.8 years). There was also no difference in end-stage revision (OR 0.95; 95 % CI, 0.33–2.79; p = 0.93; follow-up, 4–7.8 years). The standard mean of Western Ontario McMasters Universities (WOMAC) pain score was higher in the THA than in the PAO group (standardized mean difference [SMD] −0.57; 95 % CI, −0.93 – −0.21; p = 0.002; follow-up, 4–5.5 years); however, the WOMAC functional score did not differ significantly between groups (SMD −0.16; 95 % CI, −1.29–0.97; p = 0.78; follow-up, 4–5.5 years). The standard mean UCLA activity index was higher in the PAO than in the THA group (SMD 0.28; 95 % CI, 0.02–0.53; p = 0.03; follow-up, 5.9–7.3 years). Conclusions The incidence of postoperative complications and revision surgery was not different between THA and PAO groups. However, postoperative pain was less in the THA group and the activity score was higher in the PAO group in the follow-up periods. Level of evidence III; meta-analysis.

The glucose oxidation pathway is important for glucose catabolism in Klebsiella pneumoniae. Gluconic acid and 2-ketogluconic acid are intermediates of this pathway, and the production of these two chemicals has been developed in K. pneumoniae mutants. Catalysis characteristic research in this study has shown that xylose is a suitable substrate of the glucose dehydrogenase of this pathway. Here, using xylose as substrate, xylonic acid was accumulated in the broth of K. pneumoniae culture, and this process was dependent upon acidic conditions. Using a mixture of glucose and xylose as substrates, a mixture of xylonic acid and gluconic acid was produced by the Δgad mutant of K. pneumoniae; gluconic acid was synthesized early, and xylonic acid synthesis began after most glucose was consumed. Using the hydrolysate of bamboo as substrate, mixture of 33 g/L gluconic acid and 14 g/L xylonic acid were produced by K. pneumoniae Δgad. In fed-batch fermentation, 103 g/L xylonic acid was produced after 79 h culture, with a conversion ratio of 1.11 g/g. This is the first report of xylonic acid produced by K. pneumoniae. Production of xylonic acid and gluconic acid using bamboo hydrolysate is a novel approach for biomass utilization.

Expressing proteins with fusion partners improves yield and simplifies the purification process. We developed a novel fusion partner to improve the secretion of heterologous proteins that are otherwise poorly excreted in yeast. The VOA1 (YGR106C) gene of Saccharomyces cerevisiae encodes a subunit of vacuolar ATPase. We found that C-terminally truncated Voa1p was highly secreted into the culture medium, even when fused with rarely secreted heterologous proteins such as human interleukin-2 (hIL-2). Deletion mapping of C-terminally truncated Voa1p, identified a hydrophilic 28-amino acid peptide (HL peptide) that was responsible for the enhanced secretion of target protein. A purification tag and a protease cleavage site were added to use HL peptide as a multi-purpose fusion partner. The utility of this system was tested via the expression and purification of various heterologous proteins. In many cases, the yield of target proteins fused with the peptide was significantly increased, and fusion proteins could be directly purified with affinity chromatography. The fusion partner was removed by in vitro processing, and intact proteins were purified by re-application of samples to affinity chromatography.

Heterotrophic microalgae, Aurantiochytrium sp. KRS101 had a large amount of lipid (56.8% total lipids). The cells in the culture medium were easily ruptured due to thin cell wall of Aurantiochytrium sp., which facilitated in-situ fatty acid methyl esters (FAMEs) production directly from biomass. The harvested biomass had a high content of free fatty acids (FFAs), which was advantageous for glycerol-free FAMEs production. FAMEs were directly produced from Aurantiochytrium sp. KRS101 biomass (48.4% saponifiable lipids) using Novozyme 435-catalyzed in-situ esterification in dimethyl carbonate (DMC). DMC was used as a lipid extraction reagent, acyl acceptor and reaction medium. A 433.09mg FAMEs/g biomass was obtained with 89.5% conversion under the optimal condition: DMC to biomass ratio of 5:1 (v/w) and enzyme to biomass ratio of 30% (w/w) at 50°C for 12h. Glycerol could not be detected in the produced FAMEs.

The objective of vehicle aerodynamic design is on the fuel economy, reduction of the harmful emission, minimizing the vibration and noise and the driving stability of the vehicle. Especially for a sedan, the driving stability of the vehicle is the main concern of the aerodynamic design of the vehicle indeed. In this theoretical study, an evaluation algorithm of aerodynamic driving stability of a vehicle was made to estimate the dynamic stability of a vehicle at the given driving condition on a road. For the stability evaluation of a driving vehicle, CFD simulation was conducted to have the rolling, pitching and yawing moments of a model vehicle and compared the values of the moments to the resistance moments. From the case study, it is found that a model sedan running at 100 km/h in speed on a straight level road is stable under the side wind with 45 m/s in speed. But the different results may be obtained on the buses and trucks because those vehicles have the wide side area. From the case study of the model vehicle moving on 100 km/h speed with 15 m/s side wind is evaluated using the numerical algorithm drawn from the study, the value of yawing moment is 608.6 N･m, rolling moment -641 N･m and pitching moment 3.9 N･m. These values are smaller than each value of rotational resistance moment the model vehicle has, and therefore, the model vehicle’s driving stability is guaranteed when driving 100 km/h with 15 m/s side wind.

Objectives There has been a recent focus on 3D printing with regard to tissue engineering. We evaluated the efficacy of a 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial oesophageal defects. Methods MSCs from rabbit bone marrow were cultured, and a 3DP polycaprolactone (PCL) scaffold was coated with the MSCs seeded in fibrin. The fibrin/MSC-coated 3DP PCL scaffold was implanted on a 5 × 10 mm artificial oesophageal defect in three rabbits (3DP/MSC group) and 3DP PCL-only scaffolds were implanted in three rabbits (3DP-only group). Three weeks post-procedure, the implanted sites were evaluated radiologically and histologically. Results None of the rabbits showed any infection, stenosis or granulation on computed tomography. In the 3DP/MSC group, the replaced scaffolds were completely covered with regenerating mucosal epithelium and smooth muscle cells as determined by haematoxylin and eosin and Desmin staining. However, mucosal epithelium and smooth muscle cell regeneration was not evident in the 3DP-only group. Conclusions Use of the 3DP scaffold coated with MSCs seeded in fibrin resulted in successful restoration of the shape and histology of the cervical oesophagus without any graft rejection; thus, this is a promising material for use as an artificial oesophagus.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents an effective agent for the treatment of many cancers, though the majority of thyroid cancers are found to be resistant. Therefore it would be necessary to identify agents capable of increasing the sensitivity of these cancers to TRAIL-mediated cell death. Here, we examined the therapeutic effect and its underlying mechanism of combination treatment of TRAIL and histone deacetylase inhibitor, Valproic acid (VPA) in vitro using human papillary thyroid cancer (PTC) cells and in vivo using an orthotopic mouse model of PTC. TRAIL-VPA combination therapy synergistically induced apoptotic cell death in TRAIL-resistant PTC through caspase activation. In addition, downregulation of antioxidant transcription factor, Nrf2 by co-treatment of TRAIL-VPA induces cell death via suppression of Bcl-xL in vitro and in vivo; these effects were further enhanced following siRNA inhibition of these proteins in combination with TRAIL or TRAIL-VPA. Taken together, VPA sensitized TRAIL-resistant PTC cells to apoptotic cell death through involvement of Nrf2 and Bcl-xL. Thus, the combination of VPA and TRAIL may be a promising therapy for TRAIL-resistant PTC.

In this study, a wind tunnel test was conducted to measure the aerodynamic characteristics of a streamline- designed high-speed bus with the change of wind direction and speed and the result is compared with the aerodynamic performance of a commercialized high-speed bus model (Model-0) manufactured by Zyle Daewoo Bus Corp. Aero-dynamic performance of the existing rear-spoiler was tested to prove its aerodynamic effect on the test model bus. From the study, it was found that 24.6 % of the total drag of the original bus model (Model-0) was reduced on the streamline- designed model bus(model-1) without the rear-spoiler but only 14.3 % of the total drag was reduced with the spoiler on the streamlined model bus. It means that the rear spoiler does not work properly with the streamlined model bus (model-1) and should be noted that an optimum design of a rear-spoiler of a vehicle is important to reduce the induced pressure drag and increase the driving stability of a vehicle against yaw motion. The experimental outcome was also compared to the previous numerical research result to evaluate the reliability of the numerical algorithm of the aerodynamic performance analysis of a vehicle. The error rate (%) of the numerical result to the experimental output is about 5.4 % and it is due to the simplified body configuration of the numerical model bus. The drag increases at the higher yaw angle because the transparent frontal area of the model vehicle increases and the downward force increases with the yaw angle as well. It has a positive effect to the driving stability of the vehicle but the moderated downward force should be kept for the fuel economy of a vehicle.

Purpose: The purpose of this study is to analyze the energy performance by applying new technologies for passive and active control. Method: We selected new technologies for passive and active control which are based on formal study by analyzing technology applied to the High-Performance Buildings in various countries. Also, we analyzed energy saving potential for each technologies by breakdown the result of the energy saving rates in detail. Result: For the wall and roof insulating methods, preceding studies showed that up to 21% energy could be saved by improving roof insulation and applying proper outside insulation compared to non-insulation. For the windows and glazing system, preceding studies showed that Low-E glazing system could save up to 11% energy compared to single glazing system. Studies about solar and daylighting controls revealed that effective daylighting dimming control could save 13% of energy compared to uncontrolled situation. Studies on DOAS (Dedicated Outdoor Air System) showed that about 23% energy could be saved compared to standard VAV system. Studies on the active chilled beam showed that about 25% energy could be saved compared to standard VAV system and studies of applying UFAD (Under Floor Air Distribution) could consume 31% less energy than applying overhead system.

Purpose: Glazing and shading devices influence a lot on the thermal and visual environment in office buildings. Solar heat and daylight are contrary concept, therefore proper arrangement of thermal and optical performance is needed when designing a glazing and shading devices. The purpose of this study is to examine the conditions of the glazing and shading devices available for promoting the reduction of cooling loads + lighting loads and the improvement in thermal comfort and visual comfort for the summer season in an office building installed with venetian blind. Method: This study established 12 simulation cases which have different glazings and the positions of venetian blind for evaluating different thermal and optical performance. And by using EnergyPlus v8.1 and Window v7.2 program, we quantitatively analyzed cooling loads + lighting loads, thermal comfort and visual comfort in an office building installed with the glazing and shading devices. Result: Consequently, Case 9(Double Low-E+Exterior Blind) is the best arrangement of solar heat gain and daylight influx, thereby becomes the most excellent case of reducing cooling+lighting loads(46.8%) and simultaneously becomes the enhancement case in thermal comfort. Also, DGI(Daylight glare index) under clear sky conditions in summer was evaluated to be 19.6, and thereby satisfied the recommendation level of allowing visual comfort.