An Emerging Role of Micro- and Nanoplastics in Vascular Diseases.

Vascular diseases are the leading causes of death worldwide, and they are attributable to multiple pathologies, such as atherosclerosis, diabetes, and chronic obstructive pulmonary disease. Exposure to various environmental contaminants is associated with the development of various diseases, including vascular diseases. Among environmental contaminants, micro- and nanoplastics have gained attention as global environmental risk factors that threaten human health. Recently, extensive research has been conducted on the effects of micro- and nanoplastics on various human diseases, including vascular diseases. In this review, we highlight the effects of micro- and nanoplastics on vascular diseases.

Feasibility study of storing CO2 in the ocean by marine environmental impact assessment.

Since the industrial revolution, which was accompanied with the use of fossil fuels as an energy source, the content of carbon dioxide (CO2) in the atmosphere has increased. To mitigate global warming, industries that utilize fossil fuels have continuously explored new approaches to reduce CO2 emissions and convert it to alternative fuels. The ocean is a vast source of absorbed CO2 on Earth, and various studies have been conducted on the use of the ocean to reduce global CO2. This study focused on reducing CO2 in the atmosphere by storing it as bicarbonate, a form of CO2 that exists in the ocean. The optimum condition for the conversion of CO2 into bicarbonate was investigated by considering the dissolved inorganic carbon (DIC; HCO3-, CO32-, H2CO3) concentration and pH. To confirm the biological impact of this conversion, biological impact experiments were conducted under various DIC concentrations using Skeletonema japonicum, a phytoplankton present in most areas of the sea. Based on the DIC concentration (2.09 mM) of the seawater, the DIC concentrations used in the Lab-scale experiment ranged from 2.5 mM to 18.75 mM, and the concentration with the highest conversion rate (< 6.38 mM) was applied in the pilot plant. Marine environmental impact modeling was performed to observe the effect of discharge to the ocean and its movement. The results revealed a slight growth inhibition of phytoplankton at DIC concentrations higher than the base concentration. Nevertheless, the change in the DIC concentration exerted no effect on the phytoplankton growth except at extremely high concentrations. Moreover, the high DIC concentration can be diluted by the ocean current flow rate, thus counterbalancing the growth inhibition effect. The results obtained in this study demonstrate the feasibility of CO2 storage in the form of DIC, and will be helpful for further development of CO2 mitigation.

Organizing Reliable Polymer Electrode Lines in Flexible Neural Networks via Coffee Ring-Free Micromolding in Capillaries.

With an increase in the demand for smart wearable systems, artificial synapse arrays for flexible neural networks have received considerable attention. A synaptic device with a two-terminal configuration is promising for complex neural networks because of its ability to scale to a crossbar array architecture. To realize practical crossbar arrays with a high density, it is essential to achieve reliable electrode lines that act as signal terminals. However, an effective method to develop intrinsically flexible signal lines in artificial neural networks has not been developed. In this study, we achieved reliable polymer signal lines for flexible neural networks using coffee ring-free micromolding in capillaries (MIMIC). In a typical MIMIC, the outward convective flow of the polymer solution inherently deteriorates the pattern fidelity. To achieve reliable conducting polymer (CP) lines, we precisely controlled the flow of the polymer solution in the MIMIC by inducing the Marangoni force. When the convective and Marangoni flows for the solution were balanced in the MIMIC, the CP line patterns were reliably produced with high fidelity. The developed CP lines exhibited superior conductivity and high mechanical flexibility. Moreover, flexible memristor arrays consisting of CP signal lines demonstrated a high potential for realizing practical neuromorphic systems linked to artificial intelligence.

Stack LSTM-Based User Identification Using Smart Shoes with Accelerometer Data.

In this study, we propose a long short-term memory (LSTM)-based user identification method using accelerometer data from smart shoes. In general, for the user identification with human walking data, we require a pre-processing stage in order to divide human walking data into individual steps. Next, user identification can be made with divided step data. In these approaches, when there exist partial data that cannot complete a single step, it is difficult to apply those data to the classification. Considering these facts, in this study, we present a stack LSTM-based user identification method for smart-shoes data. Rather than using a complicated analysis method, we designed an LSTM network for user identification with accelerometer data of smart shoes. In order to learn partial data, the LSTM network was trained using walking data with random sizes and random locations. Then, the identification can be made without any additional analysis such as step division. In the experiments, user walking data with 10 m were used. The experimental results show that the average recognition rate was about 93.41%, 97.19%, and 98.26% by using walking data of 2.6, 3.9, and 5.2 s, respectively. With the experimental results, we show that the proposed method can classify users effectively.

Comparative phenotypic analysis of CHO clones and culture media for lactate shift.

We explored the effects of media and clonal variation on the lactate shift which can be considered as one of the desirable features in CHO cell culture. Various culture profiles with the specific growth and antibody production rates under three different media conditions in two CHO producing clones were evaluated by resorting to multivariate statistical analysis. In most cases, glutamine depletion coincided with lactate consumption, suggesting that glutaminolysis rather than glycolysis was the preferred pathway for the pyruvate supply toward lactate production. With respect to the lactate shift, high performing medium showed higher glutamate uptake, higher aspartate secretion and lower serine uptake compared to other media conditions. In addition, clone itself exhibited the desired lactate consumption more consistently accompanying with distinguishing phenotype. The clone exhibiting lactate shift produced lesser lactate in exponential phase but two-fold higher non-toxic alanine, thus leading to better culture environment. Thus, we understand the balanced selection of clone and media composition enables cells to utilize the metabolic pathways for the desired lactate shift.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain.

BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

Quantification of Valleys of Randomly Textured Substrates as a Function of Opening Angle: Correlation to the Defect Density in Intrinsic nc-Si:H.

Optical and electrical properties of hydrogenated nanocrystalline silicon (nc-Si:H) solar cells are strongly influenced by the morphology of underlying substrates. By texturing the substrates, the photogenerated current of nc-Si:H solar cells can increase due to enhanced light scattering. These textured substrates are, however, often incompatible with defect-less nc-Si:H growth resulting in lower Voc and FF. In this study we investigate the correlation between the substrate morphology, the nc-Si:H solar-cell performance, and the defect density in the intrinsic layer of the solar cells (i-nc-Si:H). Statistical surface parameters representing the substrate morphology do not show a strong correlation with the solar-cell parameters. Thus, we first quantify the line density of potentially defective valleys of randomly textured ZnO substrates where the opening angle is smaller than 130° (ρ<130). This ρ<130 is subsequently compared with the solar-cell performance and the defect density of i-nc-Si:H (ρdefect), which is obtained by fitting external photovoltaic parameters from experimental results and simulations. We confirm that when ρ<130 increases the Voc and FF significantly drops. It is also observed that ρdefect increases following a power law dependence of ρ<130. This result is attributed to more frequently formed defective regions for substrates having higher ρ<130.

Preparation and Photocatalytic Activity of Potassium- Incorporated Titanium Oxide Nanostructures Produced by the Wet Corrosion Process Using Various Titanium Alloys.

Nanostructured potassium-incorporated Ti-based oxides have attracted much attention because the incorporated potassium can influence their structural and physico-chemical properties. With the aim of tuning the structural and physical properties, we have demonstrated the wet corrosion process (WCP) as a simple method for nanostructure fabrication using various Ti-based materials, namely Ti-6Al-4V alloy (TAV), Ti-Ni (TN) alloy and pure Ti, which have 90%, 50% and 100% initial Ti content, respectively. We have systematically investigated the relationship between the Ti content in the initial metal and the precise condition of WCP to control the structural and physical properties of the resulting nanostructures. The WCP treatment involved various concentrations of KOH solutions. The precise conditions for producing K-incorporated nanostructured titanium oxide films (nTOFs) were strongly dependent on the Ti content of the initial metal. Ti and TAV yielded one-dimensional nanowires of K-incorporated nTOFs after treatment with 10 mol/L-KOH solution, whereas TN required a higher concentration (20 mol/L-KOH solution) to produce comparable nanostructures. The obtained nanostructures revealed a blue-shift in UV absorption spectra due to the quantum confinement effects. A significant enhancement of the photocatalytic activity was observed via the chromomeric change and the intermediate formation of methylene blue molecules under UV irradiation. This study demonstrates the WCP as a simple, versatile and scalable method for the production of nanostructured K-incorporated nTOFs to be used as high-performance photocatalysts for environmental and energy applications.

Effect of substrate morphology slope distributions on light scattering, nc-Si:H film growth, and solar cell performance.

Thin-film silicon solar cells are often deposited on textured ZnO substrates. The solar-cell performance is strongly correlated to the substrate morphology, as this morphology determines light scattering, defective-region formation, and crystalline growth of hydrogenated nanocrystalline silicon (nc-Si:H). Our objective is to gain deeper insight in these correlations using the slope distribution, rms roughness (σ(rms)) and correlation length (lc) of textured substrates. A wide range of surface morphologies was obtained by Ar plasma treatment and wet etching of textured and flat-as-deposited ZnO substrates. The σ(rms), lc and slope distribution were deduced from AFM scans. Especially, the slope distribution of substrates was represented in an efficient way that light scattering and film growth direction can be more directly estimated at the same time. We observed that besides a high σ(rms), a high slope angle is beneficial to obtain high haze and scattering of light at larger angles, resulting in higher short-circuit current density of nc-Si:H solar cells. However, a high slope angle can also promote the creation of defective regions in nc-Si:H films grown on the substrate. It is also found that the crystalline fraction of nc-Si:H solar cells has a stronger correlation with the slope distributions than with σ(rms) of substrates. In this study, we successfully correlate all these observations with the solar-cell performance by using the slope distribution of substrates.

Ultrasonographic evaluation of the first extensor compartment of the wrist in de Quervain's disease.

BACKGROUND: This prospective cohort study was undertaken to explore the hypothesis that the retinaculum is thicker in de Quervain's disease and to identify another landmark for the presence of the intracompartmental septum. METHODS: A case group (60 wrists) comprised of Korean female patients with unilateral de Quervain's disease and a healthy control group (60 wrists) were evaluated by ultrasonography. The case group underwent surgery for extensor retinacular release, and surgical findings were used as the reference standard. The mean extensor retinacular thickness in the case and control groups was compared using a Wilcoxon rank-sum test. A receiver operation characteristic curve was constructed for the parameter. RESULTS: The mean thickness of the extensor retinaculum was 0.94 mm (SD 0.37) in the case group and 0.35 mm (SD 0.07) in the control group, and this difference was significant. The cutoff value of the extensor retinaculum for diagnosing de Quervain's disease was 0.45 mm (sensitivity 96.3%, specificity 93.3%). Bony crests were found in all cases of presence of the intracompartmental septum and could be classified into three types according to shape. CONCLUSIONS: We concluded that the extensor retinaculum is thicker in de Quervain's disease. And the bony crest on the radial styloid can be considered a new landmark for determining the presence of an intracompartmental septum. TYPE OF STUDY AND LEVEL OF EVIDENCE: Diagnostic, level II.

Immunoglobulins M survive low-pH conditions used for virus inactivation and for elution from bioaffinity columns.

Tolerance of low pH is crucial for recombinant proteins to survive conditions that might be experienced during manufacturing such as virus inactivation and elution from bioaffinity columns. In this study, we exposed three different purified immunoglobulins M (IgMs) to pH 3.5 for 60 min at room temperature. Treated samples showed no significant aggregation or fragmentation and retained full immunoreactivity, an intact glycosylation profile, and unchanged thermal stability. Because IgMs are serious candidates for next-generation therapeutics, it is essential to know that some of them are stable at low pH.

Fed-batch CHO cell t-PA production and feed glutamine replacement to reduce ammonia production.

Industrial therapeutic protein production has been greatly improved through fed-batch development. In this study, improvement to the productivity of a tissue-plasminogen activator (t-PA) expressing Chinese hamster ovary (CHO) cell line was investigated in shake flask culture through the optimization of the fed-batch feed and the reduction of ammonia generation by glutamine replacement. The t-PA titer was increased from 33 mg/L under batch conditions to 250 mg/L with daily feeding starting after three days of culture. A commercially available fed-batch feed was supplemented with cotton seed hydrolysate and the four depleted amino acids, aspartic acid, asparagine, cysteine, and tyrosine. The fed-batch operation increased the generation of by-products such as lactate and ammonia that can adversely affect the fed-batch performance. To reduce the ammonia production, a glutamine-containing dipeptide, pyruvate, glutamate, and wheat gluten hydrolysate, were investigated as glutamine substitutes. To minimize the lag phase as the cells adjusted to the new energy source, a feed glutamine replacement process was developed where the cells were initially cultured with a glutamine containing basal medium to establish cell growth followed by feeding with a feed containing the glutamine substitutes. This two-step feed glutamine replacement process not only reduced the ammonia levels by over 45% but, in the case of using wheat gluten hydrolysate, almost doubled the t-PA titer to over 420 mg/L without compromising the t-PA product quality or glycosylation pattern. The feed glutamine replacement process combined with optimizing other feed medium components provided a simple, practical, and effective fed-batch strategy that could be applied to the production of other recombinant therapeutic proteins.

Routine barium enema prior to closure of defunctioning ileostomy is not necessary.

PURPOSE: The use of barium enemas to confirm the anastomotic integrity prior to ileostomy closure is still controversial. The purpose of the study was to determine the utility of routine contrast enema prior to ileostomy closure and its impact on patient management in patients with a low pelvic anastomosis. METHODS: One hundred forty-five patients had a temporary loop ileostomy constructed to protect a low colorectal or coloanal anastomosis following low anterior resection for rectal cancer. All patients were evaluated by physical examination, proctoscopy, and barium enema prior to ileostomy closure. RESULTS: The median time from ileostomy creation to closure was 8 months. Five (3.5%) of the 144 patients were found to have clinically relevant strictures at the colorectal anastomosis on routine barium enema. One patient (0.7%) showed anastomotic leak on their barium enema. Overall, 141 patients (97.9%) had an uncomplicated postoperative course. Postoperative complication occurred in three patients (2.1%). None of them showed abnormal barium enema finding, which suggested that routine contrast enema examination did not predict postoperative complication. CONCLUSION: Routine barium enema evaluation of low pelvic anastomoses before loop ileostomy closure did not provide any additional information for postoperative colorectal anastomotic complication.

Combined data preprocessing and multivariate statistical analysis characterizes fed-batch culture of mouse hybridoma cells for rational medium design.

We present an integrated framework for characterizing fed-batch cultures of mouse hybridoma cells producing monoclonal antibody (mAb). This framework systematically combines data preprocessing, elemental balancing and statistical analysis technique. Initially, specific rates of cell growth, glucose/amino acid consumptions and mAb/metabolite productions were calculated via curve fitting using logistic equations, with subsequent elemental balancing of the preprocessed data indicating the presence of experimental measurement errors. Multivariate statistical analysis was then employed to understand physiological characteristics of the cellular system. The results from principal component analysis (PCA) revealed three major clusters of amino acids with similar trends in their consumption profiles: (i) arginine, threonine and serine, (ii) glycine, tyrosine, phenylalanine, methionine, histidine and asparagine, and (iii) lysine, valine and isoleucine. Further analysis using partial least square (PLS) regression identified key amino acids which were positively or negatively correlated with the cell growth, mAb production and the generation of lactate and ammonia. Based on these results, the optimal concentrations of key amino acids in the feed medium can be inferred, potentially leading to an increase in cell viability and productivity, as well as a decrease in toxic waste production. The study demonstrated how the current methodological framework using multivariate statistical analysis techniques can serve as a potential tool for deriving rational medium design strategies.

Nardostachys jatamansi protects against cerulein-induced acute pancreatitis.

OBJECTIVES: Nardostachys jatamansi belonging to the family Valerianaceae has been used as a remedy for stomach and skin ailments in Korea. The effect of N. jatamansi on acute pancreatitis (AP) has not been defined. Therefore, we investigated the effect of N. jatamansi on cerulein-induced AP. METHODS: In the pretreatment group, N. jatamansi was administered orally to mice at 10 and 20 mg/kg for 5 days, and the mice were intraperitoneally injected with the stable cholecystokinin analogue cerulein hourly for 6 hours. In the posttreatment group, cerulein was injected hourly for 6 hours, and N. jatamansi was administered at the indicated time (1, 3, and 5 hours after the first cerulein injection) and dose (10 and 20 mg/kg) during the cerulein injection. Blood samples were taken 6 hours later to determine the serum amylase, the lipase, and the cytokine levels. The pancreas and the lung were rapidly removed for morphologic examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. RESULTS: Nardostachys jatamansi treatment attenuated the AP, as shown by the histological examination results of the pancreas and the lung, reductions in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and messenger RNA expressions of inflammatory mediators. CONCLUSIONS: These results suggest that N. jatamansi attenuates the severity of AP and pancreatitis-associated lung injury.

Selective GSK-3beta inhibitors attenuate the cisplatin-induced cytotoxicity of auditory cells.

Glycogen synthase kinase-3 (GSK-3) plays an important role in the regulation of apoptosis. However, the role of GSK-3 in the auditory system remains unknown. Here we examined whether the GSK-3-specific inhibitors, SB 216763 and LiCl, could protect against cisplatin-induced cytotoxicity of auditory cells. GSK-3 was activated by cisplatin treatment of HEI-OC1 cells. SB 216763 or LiCl treatments inhibited cisplatin-induced apoptosis in a dose-dependent manner and activated caspase-9, -8 and -3. In rat primary explants of the organ of Corti, SB 216763 or LiCl treatments completely abrogated the cisplatin-induced destruction of outer hair cell arrays. Administration of SB 216763 or LiCl inhibited cochlear destruction and the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in cisplatin-injected mice. Furthermore, administration of SB 216763 or LiCl reduced the thresholds of the auditory brainstem response (ABR) in cisplatin-injected mice. Collectively, these results suggest that cisplatin-induced ototoxicity might be associated with modulation of GSK-3 activation.

Gardenia jasminoides protects against cerulein-induced acute pancreatitis.

AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.

Analysis of the thermostability determinants of hyperthermophilic esterase EstE1 based on its predicted three-dimensional structure.

The three-dimensional (3D) structure of the hyperthermophilic esterase EstE1 was constructed by homology modeling using Archaeoglobus fulgidus esterase as a reference, and the thermostability-structure relationship was analyzed. Our results verified the predicted 3D structure of EstE1 and identified the ion pair networks and hydrophobic interactions that are critical determinants for the thermostability of EstE1.

Effects of supplementation of various medium components on chinese hamster ovary cell cultures producing recombinant antibody.

Thirteen vitamins, twenty amino acids, hormones, inorganic salts, and other chemical agents, which constitute typical serum-free media, were evaluated for the development of fortified medium to enhance cell growth and productivity of recombinant antibody in the cultures of the recombinant Chinese hamster ovary (rCHO) cells. Two different rCHO cell lines, rCHO-A producing recombinant antibodies against the human platelet and rCHO-B secreting recombinant antibodies against the S surface antigen of Hepatitis B, respectively, were cultivated in batch suspension mode. Concentration of interested component in the tested medium was doubled to examine the fortification effect. Growth of rCHO-A cell and its antibody production were slightly improved with addition of either choline chloride, folic acid, thiamine[Symbol: see text]HCl, or Long(TM)R(3)IGF-I. On the other hand, in the cultivation of rCHO-B cell which was more sensitive to its environmental changes, hormones such as Long(TM)R(3)IGF-I and triiodothyronine (T(3)) as well as various vitamins involving choline chloride, i-inositol, niacinamide, pyridoxine HCl, and thiamine[Symbol: see text]HCl enhanced the cell growth and antibody production. Particularly, when concentration of consuming amino acid was doubled, remarkable increase in specific productivity was served, resulting in high final antibody concentration. These results were believed to provide a fundamental strategy of medium fortification useful for improvement of recombinant antibody production in serum-free medium.

[Usefulness of urinary trypsinogen-2 dipstick test for diagnosis of acute pancreatitis].

BACKGROUND/AIMS: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis. METHODS: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls. RESULTS: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p=0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992. CONCLUSIONS: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.