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A clinical efficacy study of 0.025-inch guidewires (GWs) according to mechanical property analysis has not been reported yet. This study was designed to evaluate the clinical efficacy of a newly developed 0.025-inch GW for biliary access according to the basic mechanical property. Commercially available 0.025-inch GWs were in vitro tested based on parameters of mechanical property. Patients with naïve papilla requiring diagnostic or therapeutic ERCP were randomly assigned to an experimental 0.025-inch newly developed GW or a control 0.025-inch GW group. Technical success rate of wire-guided cannulation (WGC), difficult biliary cannulation (DBC), and adverse event rates were measured in this multicenter randomized trial. The technical success rate of primary WGC was 79.1% (151 of 191) in the experimental group and 70.8% (131 of 185) in the control group (95% two-sided confidence interval: 8.25%; p vs. 68.1%; p = 0.002). Median biliary cannulation time was shorter in the experimental group (53 s vs. 77 s; p = 0.047). The rate of DBC was more frequent in the control group (34.6% vs. 50.3% p = 0.002). Multivariate analysis revealed that control group was one of contributing factors for DBC. Overall rate of post-ERCP pancreatitis was not different (4.7% vs. 8.6%; p = 0.125). WGC using a newly developed GW with superior physical performance GW in a bench test showed similar clinical efficacy and the rate of DBC was significantly lower in experimental GW.

Bacteroidota is a group of marine polysaccharide degraders, which play a crucial role in the carbon cycle in the marine ecosystems. In this study, three novel gliding strains, designated as SS9-22T, W9P-11T, and SW1-E11T, isolated from algae and decaying wood were proposed to represent three novel species of the genus Fulvivirga. We identified a large number of genes encoding for carbohydrate-active enzymes, which potentially participate in polysaccharide degradation, based on whole genome sequencing. The 16S rRNA sequence similarities among them were 94.4–97.2%, and against existing species in the genus Fulvivirga 93.1–99.8%. The complete genomes of strains SS9-22T, W9P-11T, and SW1-E11T comprised one circular chromosome with size of 6.98, 6.52, and 6.39 Mb, respectively; the GC contents were 41.9%, 39.0%, and 38.1%, respectively. The average nucleotide identity and the digital DNA-DNA hybridization values with members in the genus Fulvivirga including the isolates were in a range of 68.9–85.4% and 17.1–29.7%, respectively, which are low for the proposal of novel species. Genomic mining in three genomes identified hundreds of carbohydrate-active enzymes (CAZymes) covering up to 93 CAZyme families and 58–70 CAZyme gene clusters, exceeding the numbers of genes present in the other species of the genus Fulvivirga. Polysaccharides of alginate, chitin, laminarin, starch, and xylan were degraded in vitro, highlighting that the three strains are rich sources of CAZymes of polysaccharide degraders for biotechnological applications. The phenotypic, biochemical, chemotaxonomic, and genomic characteristics supported the proposal of three novel species in the genus Fulvivirga, for which the names Fulvivirga ulvae sp. nov. (SS9-22T = KCTC 82072T = GDMCC 1.2804T), Fulvivirga ligni sp. nov. (W9P-11T = KCTC 72992T = GDMCC 1.2803T), and Fulvivirga maritima sp. nov. (SW1-E11T = KCTC 72832T = GDMCC 1.2802T) are proposed.

In single subcortical infarction (SSI), changes in lesion size are a major determinant of early neurological deterioration. We evaluated the association between END and infarct growth velocity (IGV) in patients with SSI. We included consecutive patients with SSI who underwent MRI within 24 h of symptom onset between 2010 and 2020. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score. IGV was calculated using the following formula: IGV (mL/h) = diffusion-weighted imaging volume (mL)/time to MRI (h). A total of 604 patients with SSI were evaluated. Multivariable logistic regression analysis showed that IGV remained significant after adjusting for confounders (aOR = 1.34, 95% CI 1.12–1.61). In a subgroup analysis based on the type of SSI, only patients with distal SSI showed an association between IGV and END (aOR = 1.64, 95% CI 1.24–2.16). In patients with proximal SSI, IGV did not show any statistical association with END. In conclusion, IGV was positively associated with END in patients with SSI. IGV should be interpreted differently in clinical settings depending on the location of the SSI lesion.

Regarding stent expansion indices, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events. We sought to evaluate the impact of various stent expansion and apposition indices by post-stent OCT on clinical outcomes and find OCT-defined optimal stent implantation criteria. A total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents with OCT guidance and final post-stent OCT analysis were included. Several stent expansion indices (MSA, MSA/average reference lumen area, MSA/distal reference lumen area, mean stent expansion, and stent expansion by linear model [stent volume/adaptive reference lumen volume]) were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization. MSA was negatively correlated with the risk of DoCE (hazard ratio [HR] 0.80 [0.68‒0.94]). However, stent expansion by linear model representing the overall volumetric stent expansion was associated with greater risk of DoCE (HR 1.02 [1.00‒1.04]). As categorical criteria, MSA 2 (HR 3.90 [1.99‒7.65]), MSA/distal reference lumen area

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine–cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan–Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.

Recently, double-root implants have been investigated using 3D-printed technology. Here, we investigated damping capacity, microcomputed tomographic (micro-CT) and histological analyses of double-root 3D-printed implants compared with single-root 3D printed implants. Single- and double-root 3D-printed implants were fabricated and placed at both sides of mandibular third and fourth premolars in four beagle dogs. The damping capacity was measured, and periapical X-rays were taken every 2 weeks for 12 weeks. The bone volume/tissue volume (BV/TV) and bone mineral density (BMD) around the implants were measured with micro-CT. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were measured in histological samples. The implant stability values between the groups were not significantly different, except at 4 and 12 weeks. The marginal bone changes were similar at the mesial and distal areas between the groups. The BV/TV and BMD values of the double-root 3D-printed implants showed no statistical difference through micro-CT analysis, but the double-root 3D-printed implants showed lower BIC and BAFO values through histomorphometric analysis compared to the single-root 3D-printed implants. Compared to single-root implants, 3D-printed double-root implants demonstrated comparable stability and bone remodeling around the fixtures, but the statistically significant bone loss in the furcation area remains problematic.

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.

The triglyceride-glucose (TyG) index has been associated with various metabolic, cardiovascular, and cerebrovascular diseases. We evaluated the association between the TyG index and early recurrent ischemic lesions (ERILs) in patients with acute ischemic stroke (AIS). We included consecutive patients diagnosed with AIS between 2010 and 2016. ERILs were defined as new diffusion-weighted imaging lesions outside the initial symptomatic lesion area. The TyG index was calculated using the following formula: log scale of fasting triglyceride × fasting glucose/2. A total of 176 patients with AIS were evaluated. In the multivariable analysis, the TyG index remained significant (adjusted odds ratio [aOR] 2.63, 95% confidence interval [CI] 1.34–5.15). This close correlation between the TyG index and ERIL was pronounced in ERIL-same group (aOR 2.84, 95% CI 1.40–5.78), but not in ERIL-different group. When comparing the relationship between the TyG index and ERIL by stroke mechanisms, only the intracranial- and extracranial-large artery atherosclerosis groups showed significantly higher TyG index values in patients with ERIL than those without. In conclusion, a higher TyG index was associated with ERIL, especially ERIL-same, in patients with AIS. The TyG index appears to be involved in ERIL occurrence by a mechanism related to atherosclerosis.

The relationship between hyperhomocysteinemia (HHcy) and obesity with low skeletal muscle mass (LMM) has not been established. We aim to assess the association between HHcy and the coexistence of obesity and LMM in asymptomatic adult population. We conducted a population-based cross-sectional study among asymptomatic individuals who underwent measurements of plasma homocysteine and body composition analysis. HHcy was defined as > 15 umol/L, obesity as body mass index ≥ 25 (kg/m2), and LMM as skeletal muscle index less than 2 SD below the sex-specific mean of young adults. The participants were classified into ‘control’, ‘obesity alone’, ‘LMM alone’, and ‘obesity with LMM’. Among 113,805 participants, the prevalence of HHcy was 8.3% in control, 8.7% in obesity alone, 10.0% in LMM alone, and 13.0% in obesity with LMM (p for trend

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. 2019R1A2C2011293) and the UK Engineering and Physical Sciences Research Council (Grant EP/P030017/1). We report a new method to optically manipulate a single dielectric particle along closed-loop polygonal trajectories by crossing a suite of all-fiber Bessel-like beams within a single water droplet. Exploiting optical radiation pressure, this method demonstrates the circulation of a single polystyrene bead in both a triangular and a rectangle geometry enabling the trapped particle to undergo multiple circulations successfully. The crossing of the Bessel-like beams creates polygonal corners where the trapped particles successfully make abrupt turns with acute angles, which is a novel capability in microfluidics. This offers an optofluidic paradigm for particle transport overcoming turbulences in conventional microfluidic chips. Publisher PDF

Lichen-forming fungi are mutualistic symbionts of green algae or cyanobacteria. We report the comparative analysis of six genomes of lichen-forming fungi in classes Eurotiomycetes and Lecanoromycetes to identify genomic information related to their symbiotic lifestyle. The lichen-forming fungi exhibited genome reduction via the loss of dispensable genes encoding plant-cell-wall-degrading enzymes, sugar transporters, and transcription factors. The loss of these genes reflects the symbiotic biology of lichens, such as the absence of pectin in the algal cell wall and obtaining specific sugars from photosynthetic partners. The lichens also gained many lineage- and species-specific genes, including those encoding small secreted proteins. These genes are primarily induced during the early stage of lichen symbiosis, indicating their significant roles in the establishment of lichen symbiosis.Our findings provide comprehensive genomic information for six lichen-forming fungi and novel insights into lichen biology and the evolution of symbiosis.

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the “severe beta-cell dysfunction” group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The “severe insulin resistance” group had higher odds of carotid artery plaque presence (aOR 1.238). The “severe insulin resistance and beta-cell dysfunction” group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p

Sargassum is one of the most important brown algal genera that can be used as food and raw material for medicinal purpose, and has various beneficial effects. As the classification of Sargassum species is currently based on their morphological characteristics, organellar genome sequences of Sargassum would provide important information for accurate identification of species and developing species-specific markers. We sequenced the complete organellar genomes of six Sargassum species, including the first complete chloroplast genome sequences of S. fulvellum, S. serratifolium, S. macrocarpum, and S. siliquastrum, and the first complete mitochondrial genome sequences of S. fulvellum, S. serratifolium, and S. macrocarpum. The chloroplast genomes of the 6 Sargassum species contained 139 protein-coding genes (PCGs), and the mitochondrial genomes possessed 37 PCGs. A comparative study was performed between the newly sequenced organellar genomes and 44 other species belonging to class Phaeophyceae. Phylogenetic relationships using PCGs shared by Phaeophyceae species were constructed with IQ-TREE 2 using the maximum likelihood method. In addition, we developed real-time PCR markers based on SNPs to distinguish the 6 Sargassum species. Our results provide useful information for establishing phylogenetic relationships between brown algae.

Various neurovascular bundle-sparing techniques have been introduced to maximize recovery of erectile function after robot-assisted radical prostatectomy (RARP). The clipless intrafascial neurovascular bundle-sparing technique aims to preserve periprostatic structures and neurovascular bundles as much as possible by avoiding clipping of the vascular pedicles. This study reports 1-year functional and oncologic outcomes and postoperative complications in 105 patients with intact preoperative erectile function who underwent a modified clipless intrafascial neurovascular bundle-sparing RARP. Intact erectile function was defined as score ≥ 21 on the Sexual Health Inventory for Men questionnaire or ability to have sexual intercourse. Median follow-up was 26.5 months (IQR 15.25–48). Postoperative erectile function recovery rates were 71.4%, 81.9%, 88.6%, 92.4%, and 94.3% at 1, 3, 6, 9, and 12 months, respectively. The rate of positive surgical margins was 16.2% overall and 11.8% in patients with stage pT2 disease. The biochemical recurrence rate was 6.7% overall. The modified clipless intrafascial neurovascular bundle-sparing technique is safe and feasible and can achieve excellent recovery of erectile function after RARP. Further large-scale prospective comparative studies are warranted.

The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.

The water channel aquaporin 4 (AQP4) regulates the flux of water across the cell membrane, maintaining cellular homeostasis. Since AQP4 is enriched in the sarcolemma of skeletal muscle, a functional defect in AQP4 may cause skeletal muscle dysfunction. To investigate a novel mechanism underlying skeletal muscle atrophy, we examined AQP4 expression and its regulation in muscle using the rotator cuff tear (RCT) model. Human and mouse AQP4 expression was significantly decreased in atrophied muscle resulting from RCT. The size and the number of myotubes were reduced following AQP4 knockdown. Atrogin 1-mediated ubiquitination of AQP4 was verified with an ubiquitination assay after immunoprecipitation of AQP4 with an anti-AQP4 antibody. In this study, we identified high mobility group box 1 (HMGB1) as a potent upstream regulator of atrogin 1 expression. Atrogin 1 expression was increased by recombinant mouse HMGB1 protein, and the HMGB1-induced atrogin 1 expression was mediated via NF-κB signaling. Our study suggests that loss of AQP4 appears to be involved in myocyte shrinkage after RCT, and its degradation is mediated by atrogin 1-dependent ubiquitination. HMGB1, in its function as a signaling molecule upstream of the ubiquitin ligase atrogin 1, was found to be a novel regulator of muscle atrophy.

Very few population-based studies have examined the epidemiology of Wilson’s disease (WD). We investigated the epidemiology of WD using the National Health Insurance Service (NHIS) database in South Korea. We analyzed not only the statistical variables of WD, but also those of WD-related diseases. WD patients were identified with the relevant International Classification of Diseases-10 code out of 50.5 million people. We used the NHIS database from 2009 to 2016 and analyzed the incidence rate, prevalence, and clinical symptoms of WD. A total of 1,333 patients were identified. The average annual incidence rate was 3.8 per million person-years. The prevalence was 38.7 per million people. The mean diagnostic age was 26.1 ± 17.2 with earlier diagnosis in men (P = 0.0003). Among the patients, 988 (74.1%) had hepatic symptoms, 510 (38.3%) had neurologic symptoms, and 601 (45.1%) had psychiatric symptoms. Before the diagnosis of WD, 350 (26.3%) had neurologic symptoms, and 427 (32%) had psychiatric symptoms. The annual mortality rate was 0.7%. Age, liver cirrhosis, and liver failure correlated with a fatal prognosis (P

Tungsten disulfide (WS2) quantum dots (QDs) embedded in polyvinylpyrrolidone (PVP) based flexible memristive devices were prepared, and those devices exhibited typical bistable electrical switching and remarkable nonvolatile memristive behaviors. Maximum electricity ON/OFF ratio obtained from the current–voltage (I-V) curves of the device is close to 104. The set voltage of the device is +0.7 V, which effectively reduced the energy consumption. The retention times extracted from data for the devices were as large as 1 × 104 s, which points to these devices having nonvolatile characteristics. Moreover, the highly flexible characteristics of the devices were demonstrated by bending the devices. The carrier transport mechanisms were explained by fitting the I-V curves, and possible operating mechanisms of the devices can be described based on the electron trapping and detrapping processes. WS2 QDs uniformly dispersed in pure transparent N, N-Dimethylformamide (DMF) were obtained by using ultrasonication and a hydrothermal process in this work.

In a previous study, we developed a new analgesic index using nasal photoplethysmography (nasal photoplethysmographic index, NPI) and showed that the NPI was superior to the surgical pleth index (SPI) in distinguishing pain above numerical rating scale 3. Because the NPI was developed using data obtained from conscious patients with pain, we evaluated the performance of NPI in comparison with the SPI and the analgesia nociception index (ANI) in patients under general anaesthesia with target-controlled infusion of propofol and remifentanil. The time of nociception occurrence was defined as when the signs of inadequate anaesthesia occurred. The median values of NPI, SPI, and ANI for 1 minute from the time of the sign of inadequate anaesthesia were determined as the value of each analgesic index that represents inadequate anaesthesia. The time of no nociception was determined as 2 minutes before the onset of skin incision, and the median value for 1 minute from that time was defined as the baseline value. In total, 81 patients were included in the analysis. NPI showed good performance in distinguishing inadequate anaesthesia during propofol-remifentanil based general anaesthesia. NPI had the highest value in terms of area under the receiver operating characteristic curve, albeit without statistical significance (NPI: 0.733, SPI: 0.722, ANI: 0.668). The coefficient of variations of baseline values of NPI, SPI, and ANI were 27.5, 47.2, and 26.1, respectively. Thus, the NPI was effective for detecting inadequate anaesthesia, showing similar performance with both indices and less baseline inter-individual variability than the SPI.

We characterized the volume kinetics of crystalloid solutions (Ringer’s lactate solution and 5% dextrose water) and colloid solutions (6% tetrastarch and 10% pentastarch) by nonlinear mixed-effects modeling in healthy volunteers. We also assessed whether the bioelectrical impedance analysis parameters are significant covariates for volume kinetic parameters. Twelve male volunteers were randomly allocated to four groups, and each group received the four fluid solutions in specified sequences, separated by 1-week intervals to avoid any carryover effects. Volunteers received 40 ml/kg Ringer’s lactate solution, 20 ml/kg 5% dextrose water, 1000 ml 6% tetrastarch, and 1000 ml 10% pentastarch over 1 h. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. Bioelectrical impedance spectroscopy (BIS, INBODY S10, InBody CO., LTD, Seoul, Korea) was also carried out at preset time points. In total, 671 hemoglobin-derived plasma dilution data points were used to determine the volume kinetic characteristics of each fluid. The changes in plasma dilution induced by administration of crystalloid and colloid solutions were well-described by the two-volume and one-volume models, respectively. Extracellular water was a significant covariate for the peripheral volume of distribution at baseline in the volume kinetic model of Ringer’s lactate solution. When the same amount was administered, the colloid solutions had ~4 times more plasma expansion effect than did the crystalloid solutions. Starches with larger molecular weights maintained the volume expansion effect longer than those with smaller molecular weights.

In the present study, a novel ZnO nanoparticles adorned nitrogen-doped carbon balls (ZnO@CBs) were successfully synthesized from polybenzoxazine and ZnO nanoparticles through a simple carbonization method. The typical wurtzite hexagonal zinc oxide phase in ZnO@CBs and degree of graphitization were revealed by the X-ray diffraction pattern. The field emission scanning electron microscopy confirmed that the synthesized carbon materials have well dispersed ball-like structure, wherein, the ZnO nanoparticles are distributed evenly on the carbon balls (CBs). The synthesized ZnO@CBs with different wt.% (20, 40, 60 and 80) and bare ZnO nanoparticles were investigated for methylene blue (MB) dye degradation experiment. The synthesized ZnO@CBs exhibited high activity in the degradation of MB. Among the different wt.% of ZnO@CBs, 60 wt.% of ZnO@CBs showed the highest MB degradation ratio (99%) with a fast degradation rate (1.65% min−1) under the following optimum conditions: 20 mg of ZnO@CBs in 50 mL of MB solution at room temperature.

Cerebral small vessel diseases (cSVDs) affect the prognosis of various types of ischemic stroke. Therefore, we evaluated the association between cSVD and the prognosis of cryptogenic stroke patients with active cancer. We enrolled patients diagnosed with cryptogenic stroke and active cancer from 2010 to 2016. Early neurological deterioration (END) was defined as a ≥ 2-point increase in the total NIHSS score or a ≥ 1-point increase in the motor NIHSS score within the first 72 h. We defined an unfavorable outcome as the modified Rankin Scale (mRS) score ≥ 3 points. We analyzed cSVD separately for each subtype including white matter hyperintensity (WMH), silent brain infarct (SBI), and cerebral microbleed (CMB). A total of 179 cryptogenic stroke patients with active cancer were evaluated. In the multivariable analysis, SBI was significantly associated with END (adjusted odds ratio = 3.97, 95% confidence interval: 1.53–10.33). This close relationship between SBI and END increased proportionally with an increase in SBI burden. However, WMH and CMB showed no significant association with END. None of the cSVD subtypes showed a statistically significant relationship with the 3-month unfavorable outcome. SBI was the only parameter closely associated with END in cryptogenic stroke patients with active cancer.

Luminescent inorganic lead halide perovskite nanoparticles lack stability in aqueous solutions, which limits their application to optical sensors. Here, hybrid CsPbBr3-loaded MIP nanogels were developed with enhanced stability in aqueous media. Multifunctional MIP nanogels with antioxidant function and hydrophobic cavities were synthesized from HEMA derivatives in the presence of roxithromycin as a template. The CsPbBr3 nanoparticles were loaded into pre-synthesized MIP nanogels via in-situ synthesis with a size distribution of 200 nm. The developed CsPbBr3-nanogel exhibit excellent stability to air/moisture and enhanced stability toward an aqueous solvent. The developed CsPbBr3-loaded MIP nanogels showed a selective and sensitive detection of ROX with a limit of detection calculated to be 1.7 × 10− 5 µg/mL (20.6 pM). The developed CsPbBr3-loaded MIP antioxidant-nanogels were evaluated on practical application for quantitative determination of ROX antibiotic in animal-derived food products with excellent analytical performance. The detection of ROX in animal-derived food products showed good recovery results making them an ideal candidate for sensing ROX.

Osteoporosis and sarcopenia are substantially interrelated with shared cardiovascular risk factors. However, the relationship between osteosarcopenia and coronary artery disease is largely unexplored. We aimed to investigate the association between osteosarcopenia and coronary artery calcification (CAC) scores in asymptomatic adults. A total of 5969 asymptomatic adults without cardiovascular disease who underwent a health examination including estimation of CAC scores by cardiac tomography were analyzed. Osteoporosis was defined as low bone mineral density T-score ≤ − 2.5 standard deviation, and sarcopenia as appendicular skeletal muscle mass 2 for women and 2 for men, and osteosarcopenia as the copresence of both osteoporosis and sarcopenia. Participants were divided into four groups according to the presence of osteoporosis and/or sarcopenia as control, sarcopenia alone, osteoporosis alone, and osteosarcopenia. Prevalence of CAC was 22.0% in control, 23.6% in sarcopenia alone, 38.5% in osteoporosis alone, and 48.3% in osteosarcopenia group, with the osteosarcopenia group showing the highest (p p 0 (odds ratio [OR] 2.868; 95% confidence interval [CI] 1.717–4.790). Furthermore, subjects with osteosarcopenia had a significant risk of moderate-to-extensive CAC (CAC score ≥ 100) (OR 2.709; 95% CI 1.128–6.505). We demonstrated that osteosarcopenia was independently associated with a higher prevalence of subclinical coronary atherosclerosis. Our results suggest osteosarcopenia as a predisposing factor for coronary heart disease.

3D printing technology has been gradually applied to various areas. In the present study, 3D-printed implants were fabricated with direct metal laser sintering technique for a dental single root with titanium. The 3D implants were allocated into following groups: not treated (3D-None), sandblasted with a large grit and acid-etched (3D-SLA), and target-ion-induced plasma-sputtered surface (3D-TIPS). Two holes were drilled in each tibia of rabbit, and the three groups of implants were randomly placed with a mallet. Rabbits were sacrificed at two, four, and twelve weeks after the surgery. Histologic and histomorphometric analyses were performed for the evaluation of mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupancy (mBAFO), osteoid area fraction occupancy (OAFO), and total bone area fraction occupancy (tBAFO) in the inner and outer areas of lattice structure. At two weeks, 3D-TIPS showed significantly higher inner and outer tBIC and inner tBAFO compared with other groups. At four weeks, 3D-TIPS showed significantly higher outer OIC than 3D-SLA, but there were no significant differences in other variables. At twelve weeks, there were no significant differences. The surface treatment with TIPS in 3D-printed implants could enhance the osseointegration process in the rabbit tibia model, meaning that earlier osseointegration could be achieved.

Knee cartilage is in an aqueous environment filled with synovial fluid consisting of water, various nutrients, and ions to maintain chondrocyte homeostasis. Aquaporins (AQPs) are water channel proteins that play an important role in water exchange in cells, and AQP1, -3, and -4 are known to be expressed predominantly in cartilage. We evaluated the changes in AQP expression in chondrocytes from human knee articular cartilage in patients of different ages and identified the key factor(s) that mediate age-induced alteration in AQP expression. The mRNA and protein expression of AQP1, -3 and -4 were significantly decreased in fibrocartilage compared to hyaline cartilage and in articular cartilage from older osteoarthritis patients compared to that from young patients. Gene and protein expression of AQP1, -3 and -4 were altered during the chondrogenic differentiation of C3H10T1/2 cells. The causative factors for age-associated decrease in AQP included H2O2, TNFα, and HMGB1 for AQP1, -3, and -4, respectively. In particular, the protective effect of AQP4 reduction following HMGB1 neutralization was noteworthy. The identification of other potent molecules that regulate AQP expression represents a promising therapeutic approach to suppress cartilage degeneration during aging.

A total of 24 Colletotrichum isolates were isolated from diseased Japanese plum (Prunus salicina) fruits showing chlorotic regions with whitish-brown sunken necrotic lesions and phylogenetic relationships among the collected Colletotrichum isolates were determined. A subset of 11 isolates was chosen for further taxonomic study based on morphology and molecular characteristics identified using the internal transcribed spacer (ITS) and beta-tubulin (TUB2) genes. Isolates in the C. acutatum complex were analyzed using partial sequencing of five gene regions (ITS, GAPDH, ACT, TUB2, and CHS), and C. gloeosporioides sensu lato (s.l.) isolates were analyzed using seven gene regions (ITS, TUB2, GAPDH, ACT, CAL, CHS-1, and ApMat). Morphological assessments in combination with phylogenetic analysis delineated four species of Colletotrichum including C. gloeosporioides sensu stricto (s.s.), C. nymphaeae, C. foriniae, and C. siamense; these data identify Colletotrichum fioriniae and C. siamense two new species associated with plum anthracnose in South Korea. Finally, the pathogenicity of these four species in the development of plum anthracnose in South Korea was confirmed by inoculations of plum fruit.

The primary purpose was to examine the relationship between the muscle architectural characteristics of short and long-distance cyclist—including muscle thickness, fascicle angle, and fascicle length—of the anterior thigh and posterior leg and its impact in 20-s cycling power. The secondary purpose was to clarify the muscle variables that predict the cycling power by using ultrasonography to measure the muscle architectural characteristics. Twenty-four varsity cyclists participated in this study, of whom 12 were short-distance cyclists and 12 were long-distance cyclists. B-mode ultrasonography was used to measure muscle architecture parameters. A cycle ergometer was used to measure the cycling power. The rectus femoris, vastus medialis, and medial head of gastrocnemius were significantly thicker in short-distance cyclists than in long-distance cyclists at every site (p

Dipeptidyl peptidase-4 inhibitors (DPP4i) are antidiabetic medications that prevent cleavage of incretin hormones by dipeptidyl peptidase-4 (DPP4). DPP4 is ubiquitously expressed, and its hepatic DPP4 expression is upregulated under non-alcoholic steatohepatitis (NASH) conditions. We investigated the effect of DPP4i treatment on NASH pathogenesis, as well as its potential underlying molecular mechanisms. Mice were randomly divided into three groups: Group 1, chow-fed mice treated with vehicle for 20 weeks; Group 2, high-fat, high-fructose, and high-cholesterol Amylin liver NASH (AMLN) diet-fed mice treated with vehicle for 20 weeks; Group 3, AMLN diet-fed mice treated with vehicle for the first 10 weeks, followed by the DPP4i teneligliptin (20 mg/kg/day) for additional 10 weeks. DPP4i administration reduced serum liver enzyme and hepatic triglyceride levels and markedly improved hepatic steatosis and fibrosis in the AMLN diet-induced NASH model. In vivo, NASH alleviation significantly correlated with the suppression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated apoptosis and downregulated hepatic DPP4 expression. In vitro, DPP4i treatment significantly decreased the markers of TRAIL receptor-mediated lipoapoptosis and suppressed DPP4 expression in palmitate-treated hepatocytes. In conclusion, DPP4i may efficiently attenuate the pathogenesis of AMLN diet-induced NASH in mice by suppressing lipotoxicity-induced apoptosis, possibly by modulating hepatic DPP4 expression.

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27–0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12–2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10–3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51–0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33–0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19–1.84, Ptrend = 4 × 10−4, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progression-free survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes.

Algae-bacteria interaction is one of the main factors underlying the formation of harmful algal blooms (HABs). The aim of this study was to develop a genome-wide high-throughput screening method to identify HAB-influenced specific interactive bacterial metabolites using a comprehensive collection of gene-disrupted E. coli K-12 mutants (Keio collection). The screening revealed that a total of 80 gene knockout mutants in E. coli K-12 resulted in an approximately 1.5-fold increase in algal growth relative to that in wild-type E. coli. Five bacterial genes (lpxL, lpxM, kdsC, kdsD, gmhB) involved in the lipopolysaccharide (LPS) (or lipooligosaccharide, LOS) biosynthesis were identified from the screen. Relatively lower levels of LPS were detected in these bacteria compared to that in the wild-type. Moreover, the concentration-dependent decrease in microalgal growth after synthetic LPS supplementation indicated that LPS inhibits algal growth. LPS supplementation increased the 2,7-dichlorodihydrofluorescein diacetate fluorescence, as well as the levels of lipid peroxidation-mediated malondialdehyde formation, in a concentration-dependent manner, indicating that oxidative stress can result from LPS supplementation. Furthermore, supplementation with LPS also remarkably reduced the growth of diverse bloom-forming dinoflagellates and green algae. Our findings indicate that the Keio collection-based high-throughput in vitro screening is an effective approach for the identification of interactive bacterial metabolites and related genes.

The harmful effects of excessive mechanical loading on diabetic neuropathy and the reason diabetic neuropathic symptoms are common in feet are unclear. In this study, the hind paw suspension treadmill exercise model was used in rats to investigate whether mechanical loading applied to the front paws precipitates neuropathic pain, especially in diabetic conditions. Thirty-two rats were divided into six groups according to the presence of diabetes (DM) and the intensity of mechanical loading applied to the front paws: DM-Hi (high-intensity); DM-Lo (low-intensity); DM-No (non-mechanical loading); Sham-Hi; Sham-Lo; and Sham-No. DM was induced by streptozotocin injection. For high-intensity or low-intensity mechanical loading, treadmill walking exercise was conducted with or without hind paw suspension, respectively. The mechanical withdrawal threshold of the front paw decreased significantly after 8 weeks only in the DM mechanical loading groups (DM-Hi and DM-Lo), and high-intensity loading more significantly decreased the front-paw withdrawal threshold than low-intensity loading. In the DM-Hi group only, macrophage migration inhibitory factor (MIF) increased significantly, and intra-epidermal nerve fibers (IENF) in the front paws decreased significantly. In diabetic conditions, mechanical overloading such as excessive walking is likely to precipitate mechanical allodynia and damage IENF¸ which could explain why diabetic neuropathic symptoms are common in feet. This finding might be related to up-regulation of intracellular signaling cascades such as MIF, rather than inflammatory processes.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31–40% higher than that in the AD group (cortex: 40%, p p p p > 0.05) and 3–14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aβ pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.

Meta-analysis can be applied to study the effectiveness of the summary estimates for experimental papers, producing objective and unbiased results. We investigated the effects of phosphoinositide-3-kinase (PI3K) on the inflammatory profile in allergic mouse models, which are currently under development in signal transduction materials. PubMed, EMBASE and Web of Science databases were searched for relevant literature using the search terms “ PI3K inhibitor” and “allergy” or “asthma”. Cochrane Review Manager and R were used for handling continuous variables. The primary outcomes of the inflammatory profile were divided into cell counts and inflammatory cytokines. We used a random effects model to draw a forest plot. Through the database search and subsequent selection, 17 articles were identified. Regarding the cell counts, both the PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced the total cell counts, eosinophils, neutrophils and lymphocytes. In contrast to PI3K-δ inhibitors, PI3K pan-inhibitors effectively reduced macrophages. Regarding the inflammatory cytokines, PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced total IgE, IL-4, IL-5, IL-13, TNF-α, IL-1β, VEGF and had no effect on IL-6. Compared to the PI3K pan-inhibitors, which block all pathways, selective PI3K-δ inhibitors are expected to be relatively less toxic. Regarding the efficacy, PI3K-δ inhibitors have at least the same or better efficacy than PI3K pan-inhibitors in effector cells and inflammatory mediators.

The purposes were to calculate total voxel volume of the entire capsulo-synovial enhanced portion on contrast-enhanced (CE) MRI in adhesive capsulitis, and to investigate its association with glenohumeral joint volume and passive range of motions (ROMs), which are a well-known diagnostic reference standard and clinical hallmark of this condition. Medical records of 169 consecutive patients who underwent ultrasound-guided intraarticular injection with adhesive capsulitis and CE-MRI to exclude other mimicking shoulder diseases were retrospectively reviewed. To calculate total voxel volume of entire capsulo-synovial enhanced portion on CE-MRI, voxel-based 3-dimensional (3D) segmentation was obtained semi-automatically using Fiji, an open-source image processing software. Pearson’s correlation coefficients were analyzed. Sixty patients who met eligibility criteria were included. Total voxel volume showed a significant inverse correlation with the glenohumeral joint volume (r = −0.528, P r = −0.407, P = 0.001; r = −0.342, P = 0.007; r = −0.275, P = 0.034, respectively). Intra-observer and inter-observer reliabilities, measured by intraclass correlation coefficients (ICC), were excellent (ICC = 0.87 and 0.77, respectively). This study’s results indicate that voxel-based 3D segmentation of entire capsulo-synovial enhanced portion from CE-MRI can represent the severity of clinical impairments, such as obliterated joint volume and limited passive ROMs in adhesive capsulitis.

Although skeletal muscle plays a crucial role in metabolism and influences aging and chronic diseases, little is known about the genetic variations with skeletal muscle, especially in the Asian population. We performed a genome-wide association study in 2,046 participants drawn from a population-based study. Appendicular skeletal muscle mass was estimated based on appendicular lean soft tissue measured with a multi-frequency bioelectrical impedance analyzer and divided by height squared to derive the skeletal muscle index (SMI). After conducting quality control and imputing the genotypes, we analyzed 6,391,983 autosomal SNPs. A genome-wide significant association was found for the intronic variant rs138684936 in the NEB and RIF1 genes (β = 0.217, p = 6.83 × 10–9). These two genes are next to each other and are partially overlapped on chr2q23. We conducted extensive functional annotations to gain insight into the directional biological implication of significant genetic variants. A gene-based analysis identified the significant TNFSF9 gene and confirmed the suggestive association of the NEB gene. Pathway analyses showed the significant association of regulation of multicellular organism growth gene-set and the suggestive associations of pathways related to skeletal system development or skeleton morphogenesis with SMI. In conclusion, we identified a new genetic locus on chromosome 2 for SMI with genome-wide significance. These results enhance the biological understanding of skeletal muscle mass and provide specific leads for functional experiments.

Peri-implantitis is an inflammatory disease that results in bone destruction around dental implants. A preclinical study using beagle models is frequently performed prior to clinical application in dentistry. Previously, we proposed an immediate peri-implantitis experimental model with a shorter experimental duration and less expense than the conventional experimental model. However, the differences in the regenerative outcomes between the immediate and conventional models were not fully revealed. In this study, we aimed to compare the regenerative outcomes between both models when ex vivo BMP2 gene therapy using autologous periodontal ligament stem cells (B2/PDLSCs) was applied to peri-implantitis defects. The results showed that the defect depths were significantly different between both models. New bone formation occurred in both models, but there were significant differences between the models. More than 70% of the defects were filled with newly formed bone in the conventional model, whereas 30–40% of the defects were filled in the immediate model. However, after adjustment for the differences in the defect depths between the models, the statistically significant differences in the regenerative outcomes between the models were lost. In conclusion, the inferior regenerative outcome of an immediate peri-implantitis model at B2/PDLSCs transplantation resulted from the defect depths, not the model itself.

In contrast to obesity, studies on the relationship between underweight and pulmonary function are still sparse. Thus, the objective of this study was to investigate the effect of being underweight on pulmonary function in a general population without apparent lung disease. A total of 282,135 retrospective cohort subjects between January 2012 and December 2014 in Korea were included. Using multivariate-adjusted analysis, the relationship between body mass index (BMI) and pulmonary function were assessed. Underweight individuals represented 5.5% of the total study population (n = 282,135), with most (87.9%) of them being females. Compare to normal weight and obese, underweight was associated with decreased pulmonary function. Forced expiratory volume in first second (FEV1), predicted FEV1 (%), forced vital capacity (FVC), predicted FVC (%), and peak expiratory flow (PEF) were lower in the underweight group than those in other groups after adjusting for age, sex, height, status of smoking, frequency of vigorous exercise, diabetes, and high-sensitivity C-reactive protein (hsCRP) (P P for trend

Urinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.

The rice blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae, Magnaporthe grisea), a member of the order Magnaporthales in the class Sordariomycetes, is an important plant pathogen and a model species for studying pathogen infection and plant-fungal interaction. In this study, we generated genome sequence data from five additional Magnaporthales fungi including non-pathogenic species, and performed comparative genome analysis of a total of 13 fungal species in the class Sordariomycetes to understand the evolutionary history of the Magnaporthales and of fungal pathogenesis. Our results suggest that the Magnaporthales diverged ca. 31 millon years ago from other Sordariomycetes, with the phytopathogenic blast clade diverging ca. 21 million years ago. Little evidence of inter-phylum horizontal gene transfer (HGT) was detected in Magnaporthales. In contrast, many genes underwent positive selection in this order and the majority of these sequences are clade-specific. The blast clade genomes contain more secretome and avirulence effector genes, which likely play key roles in the interaction between Pyricularia species and their plant hosts. Finally, analysis of transposable elements (TE) showed differing proportions of TE classes among Magnaporthales genomes, suggesting that species-specific patterns may hold clues to the history of host/environmental adaptation in these fungi.

One of the challenges in developing Lithium anodes for Lithium ion batteries (LIB) is controlling the formation of Li dendrites during cycling of the battery. Nanostructuring and nanopatterning of electrodes shows a promising way to suppress the growth of Li dendrites. However, in order to control this behavior, a fundamental understanding of the effect of nanopatterning on the electro-mechanical properties of Li metal is necessary. In this paper, we have investigated the mechanical and wear properties of Li metal using Atomic Force Microscopy (AFM) in an airtight cell. By using different load regimes, we determined the mechanical properties of Li metal. We show that as a result of nanopatterning, Li metal surface underwent work hardening due to residual compressive stress. The presence of such stresses can help to improve cycle lifetime of LIBs with Li anodes and obtain very high energy densities. Keywords: Nanopatterning, mechanical properties, Li anode, Lithium ion batteries

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, insulin resistance, and inflammation. Here, we report the crystal structures of PPARγ in complex with lobeglitazone, a novel PPARγ agonist, and with rosiglitazone for comparison. The thiazolidinedione (TZD) moiety of lobeglitazone occupies the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) in ligand-binding domain as the TZD moiety of rosiglitazone does. However, the elongated p-methoxyphenol moiety of lobeglitazone interacts with the hydrophobic pocket near the alternate binding site of PPARγ. The extended interaction of lobeglitazone with the hydrophobic pocket enhances its binding affinity and could affect the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARγ at Ser245 (in PPARγ1 numbering; Ser273 in PPARγ2 numbering). Lobeglitazone inhibited the phosphorylation of PPARγ at Ser245 in a dose-dependent manner and exhibited a better inhibitory effect on Ser245 phosphorylation than rosiglitazone did. Our study provides new structural insights into the PPARγ regulation by TZD drugs and could be useful for the discovery of new PPARγ ligands as an anti-diabetic drug, minimizing known side effects.

TiNb6O17 and TiNb2O7 were synthesized using a solid-state method. The techniques were used to assess the electrochemical performance and lithium diffusion kinetics of TiNb6O17 related to the unit cell volume with TiNb2O7. The charge-discharge curves and cyclic voltammetry revealed TiNb6O17 to have a similar redox potential to TiNb2O7 as well as a high discharge capacity. The rate performance of TiNb6O17 was measured using a rate capability test. SSCV and EIS showed that TiNb6O17 had higher lithium diffusion coefficients during the charging. From GITT, the lithium diffusion coefficients at the phase transition region showed the largest increase from TiNb2O7 to TiNb6O17.

Electrochemical water splitting is one of the most promising systems by which to store energy produced from sustainable sources, such as solar and wind energy. Designing robust and stable electrocatalysts is urgently needed because of the relatively sluggish kinetics of the anodic reaction, i.e. the oxygen evolution reaction (OER). In this study, we investigate the anomalous in situ activation behaviour of carbon-supported Ni2P nanoparticles (Ni2P/C) during OER catalysis in alkaline media. The activated Ni2P/C shows an exceptionally high activity and stability under OER conditions in which the overpotential needed to achieve 10 mA cm−2 was reduced from approximately 350 mV to approximately 300 mV after 8,000 cyclic voltammetric scans. In situ and ex situ characterizations indicate that the activity enhancement of Ni2P catalysts is due to a favourable phase transformation of the Ni centre to β-NiOOH, including increases in the active area induced by structural deformation under the OER conditions. These findings provide new insights towards designing transition metal/phosphide-based materials for an efficient water splitting catalyst.

Methylglyoxal (MG) is a reactive dicarbonyl intermediate and a precursor of advanced glycation end products (AGEs). The authors investigated the role played by AGEs in muscle myopathy and the amelioration of its effects by curcumin and gingerol. In addition to producing phenotypical changes, MG increased oxidative stress and reduced myotube formation in C2C12 cells. RAGE (receptor for AGEs) expression was up-regulated and MYOD and myogenin (MYOG) expressions were concomitantly down-regulated in MG-treated cells. Interestingly, AGE levels were higher in plasma (~32 fold) and muscle (~26 fold) of diabetic mice than in control mice. RAGE knock-down (RAGEkd) reduced the expressions of MYOD and MYOG and myotube formation in C2C12 cells. In silico studies of interactions between curcumin or gingerol and myostatin (MSTN; an inhibitor of myogenesis) and their observed affinities for activin receptor type IIB (ACVRIIB) suggested curcumin and gingerol reduce the interaction between MSTN and ACVRIIB. The findings of this study suggest enhanced AGE production and subsequent RAGE-AGE interaction obstruct the muscle development program, and that curcumin and gingerol attenuate the effect of AGEs on myoblasts.

ER retention receptor is a seven trans-membrane protein that plays pivotal roles in function and integrity of endoplasmic reticulum (ER). Insertional mutagenesis of Magnaporthe oryzae identified MoERR1 as a pathogenicity gene encoding putative ER retention receptor orthologous to ERD2 in Saccharomyces cerevisiae. Search through the genome identified that M. oryzae possesses another ortholog of ERD2, which is designated as MoERR2. When MoERR1 and MoERR2 were tagged with GFP, both were localized to ER. Targeted disruption of MoERR1 showed pleiotropic effects on phenotypes, while deletion of MoERR2 had no effect on phenotypes we examined. The disruption mutant of MoERR1 showed growth retardation and produced significantly reduced number of conidia with aberrant morphology. Appressoria from the mutant were unable to penetrate into plant tissues presumably due to defect in cell wall integrity, thereby rendering the mutant non-pathogenic. The MoERR1 mutant also appeared to display abnormal ER structure and mis-regulation of genes involved in chaperone function and unfolded protein response under ER stress condition. Taken together, these results suggest that MoERR1 is a ER retention receptor required for function and integrity of ER, and that MoERR1-mediated ER functionalities are essential for fungal development and pathogenesis.

A series of new functionalized 3-indolylindolin-2-ones, 3-(1-methylpyrrol-2-yl)indolin-2-ones, and 3-(thiophen-2-yl)indolin-2-ones were synthesized by using novel indium (III)-catalysed reaction of various 3-diazoindolin-2-ones with indoles, 1-methylpyrrole, or thiophene via one-pot procedure. The newly synthesized compounds were characterized and screened for their in vitro antibacterial activity against various Staphylococcus species, including methicillin-resistant Staphylococcus aureus. results revealed that five compounds KS15, KS16, KS17, KS19, and KS20 exhibited potent and specific antibacterial activity against Staphylococcus species albeit inactive against Gram-negative bacteria. Especially, compounds exhibited superior antibacterial potency against Staphylococcus epidermidis compared to the reference drug streptomycin. The most potential compound KS16 also increased the susceptibility of Staphylococcus aureus to ciprofloxacin, gentamicin, kanamycin, and streptomycin. Among them, KS16 was found to be a synergistic compound with gentamicin and kanamycin. Furthermore, the cellular level of autolysin protein was increased from the KS16-treated Staphylococcus aureus cells. Finally, in vitro CCK-8 assays showed that KS16 exhibited no cytotoxicity at the minimum inhibitory concentrations used for killing Staphylococcus species. From all our results, novel oxindole compounds directly have lethal action or boost existing antibiotic power with the reduction of doses and toxicity in the treatment of multidrug-resistant Staphylococcus species.

The regulatory properties of pyruvate kinase M2 isoform (PKM2), the key glycolytic enzyme, influence altered energy metabolism including glycolysis in cancer. In this study, we found that PKM2 was highly expressed in patients with ulcerative colitis or colorectal cancer (CRC). We then investigated the effectiveness of conditionally ablating PKM2 in Lgr5+ intestinal stem cells (ISC) using a mouse model of colitis-associated CRC (AOM plus DSS). Tamoxifen-inducible Lgr5-driven deletion of PKM2 in ISC (PKM2ΔLgr5-Tx) significantly promoted tumor incidence and size in the colon and lower body weight compared with findings in vehicle-treated mice (PKM2ΔLgr5-Veh). Histopathologic analysis revealed considerable high-grade dysplasia and adenocarcinoma in the colon of PKM2ΔLgr5-Tx mice while PKM2ΔLgr5-Veh mice had low- and high-grade dysplasia. Loss of PKM2 was associated with dominant expression of PKM1 in Lgr5+ ISC and their progeny cells. Further, the organoid-forming efficiency of whole cancer cells or Lgr5+ cells obtained from colon polyps of PKM2ΔLgr5-Tx mice was significantly increased when compared with PKM2ΔLgr5-Veh mice. Cancer organoids from PKM2ΔLgr5-Tx mice exhibited increased mitochondrial oxygen consumption and a shift of metabolites involved in energy metabolism. These findings suggest that loss of PKM2 function in ISC promotes colitis-associated CRC.