Search

Movement disorders associated with glial fibrillary acidic protein (GFAP) autoantibodies have rarely been reported as ataxia or tremors. A 32-year-old man with headache and fever, initially diagnosed with viral meningoencephalitis, showed gradual improvement with empirical treatment. Two weeks after the illness, he suddenly developed orofacial, tongue, and neck dyskinesia accompanied by oculomotor abnormalities, which developed into severe generalized choreoballism. Brain magnetic resonance imaging (fluid-attenuated inversion recovery) showed signal hyperintensities in the bilateral globus pallidus interna. The clinical picture suggested an acute inflammatory trigger of secondary autoimmune encephalitis. The autoimmune antibody test was positive for GFAP, with the strongest reactivity in the cerebrospinal fluid (CSF) before treatment and decreased reactivity in serial CSF examinations during immunotherapy. Dyskinesia gradually improved to the extent that it could be controlled with only oral medications. This patient presented with parainfectious GFAP meningoencephalitis with distinctive clinical features and imaging findings.

Recent advances in DNA nanotechnology led the fabrication and utilization of various DNA assemblies, but the development of a method to control their global shapes and mechanical flexibilities with high efficiency and repeatability is one of the remaining challenges for the realization of the molecular machines with on-demand functionalities. DNA-binding molecules with intercalation and groove binding modes are known to induce the perturbation on the geometrical and mechanical characteristics of DNA at the strand level, which might be effective in structured DNA assemblies as well. Here, we demonstrate that the chemo-mechanical response of DNA strands with binding ligands can change the global shape and stiffness of DNA origami nanostructures, thereby enabling the systematic modulation of them by selecting a proper ligand and its concentration. Multiple DNA-binding drugs and fluorophores were applied to straight and curved DNA origami bundles, which demonstrated a fast, recoverable, and controllable alteration of the bending persistence length and the radius of curvature of DNA nanostructures. This chemo-mechanical modulation of DNA nanostructures would provide a powerful tool for reconfigurable and dynamic actuation of DNA machineries.

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

Cytochrome P450 1A1 (CYP1A1) is a member of a subfamily of enzymes involved in the metabolism of both endogenous and exogenous substrates and the chemical activation of xenobiotics to carcinogenic derivatives. Here, the effects of nicotine, a major psychoactive compound present in cigarette smoke, on CYP1A1 expression and human hepatocellular carcinoma (HepG2) cell proliferation were investigated. Nicotine stimulated CYP1A1 expression via the transcription factors, activator protein 1, nuclear factor-kappa B, and the aryl hydrocarbon receptor (AhR) signaling pathway. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase, as well as RelA (or p65), mediated the upregulation of CYP1A1 of nicotine in HepG2 cells. The antioxidant compound, N-acetyl-cysteine, abrogated nicotine-activated production of reactive oxygen species and inhibited CYP1A1 expression by nicotine. Furthermore, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was inhibited by diphenyleneiodonium (an NADPH oxidase inhibitor). Thus, these results demonstrated that AhR played an important role in nicotine-induced CYP1A1 expression. Additionally, liver hepatocellular carcinoma HepG2 cells treated with nicotine exhibited markedly enhanced proliferation via CYP1A1 expression and Akt activation.

Ark shell protein hydrolysates-derived peptides showing anti-adipogenic effect were purified and identified using consecutive chromatographic techniques and tandem mass spectrometry. Two anti-adipogenic peptides LLRLTDL (843.02 Da) and GYALPCDCL (954.13 Da) were found to be highly effective for lipid accumulation inhibition in mouse bone marrow-derived mesenchymal stem cells differentiation into adipocyte. The inhibitory activity of LLRLTDL and GYALPCDCL for lipid accumulation was 48.53 % and 46.22 % at 100 μM, respectively. During adipocyte differentiation, two anti-adipogenic peptides LLRLTDL and GYALPCDCL significantly inhibited intracellular reactive oxygen species (ROS) generation by 47.39 % and 49.77 % at 100 μM. In addition, LLRLTDL and GYALPCDCL treatment increased cellular antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, LLRLTDL and GYALPCDCL suppressed proinflammatory cytokine productions, including tumor necrosis factor-α, interleukin-1β and -6. These results suggest that LLRLTDL and GYALPCDCL could modulate adipocyte differentiation and be useful as anti-obesity ingredients or functional foods.

Objectives Ginkgolide C (GGC) isolated from Ginkgo biloba (Ginkgoaceae) leaf can demonstrate pleiotropic pharmacological actions. However, its anti-oncogenic impact in non-small cell lung cancer (NSCLC) model has not been reconnoitered. As signal transducer and activator of transcription 3 (STAT3) cascade can promote tumour growth and survival, we contemplated that GGC may interrupt this signalling cascade to expend its anti-cancer actions in NSCLC. Methods The effect of GGC on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation and apoptosis was examined. The in-vivo effect of GGC on the growth of human NSCLC xenograft tumours in athymic nu/nu female mice was also investigated. Key findings GGC attenuated the phosphorylation of STAT3 and STAT3 upstream kinases effectively. Exposure to pervanadate modulated GGC-induced down-regulation of STAT3 activation and promoted an elevation in the level of PTPε protein. Indeed, silencing of the PTPε gene reversed the GGC-promoted abrogation of STAT3 activation and apoptosis. Moreover, GGC exposure significantly reduced NSCLC tumour growth without demonstrating significant adverse effects via decreasing levels of p-STAT3 in mice tissues. Conclusions Overall, the findings support that GGC may exhibit anti-neoplastic actions by mitigation of STAT3 signalling cascade in NSCLC.

Maize straw- and rice husk-derived biochars were produced in a simple metal kiln without automated control. Their characteristics and effects on crop productivity were investigated in three fields in Nepal. The maximum temperature inside the kiln reached ~ 450 °C; the charring reaction was maintained for 90 min and 10 h for maize straw- and rice husk-derived biochars, respectively, until 30 °C was reached. The physicochemical properties of the biochars were similar to those of biochars manufactured previously in electric furnaces with automated control. Compared with control soil, incorporation of maize straw- and/or rice husk-derived biochars into soil significantly (p

Daecheongdo and Socheongdo Islands are located in the West Sea of Korea, 210 km away from land, and are military border areas very close to North Korea, making them difficult to access. Although the ecosystem of the islands is relatively well preserved due to the lack of accessibility, research on fungi of the regions is insufficient. Therefore, we aimed to investigate indigenous fungi in these geographically and geopolitically constrained regions. A survey of the indigenous fungal diversity of the islands was conducted in 2018. All specimens were identified at the species level based on morphological and molecular analyses. Among them, six macrofungi—namely, Agaricus menieri, Crepidotus praecipuus, Dichomitus squalens, Hortiboletus amygdalinus, Melanoleuca friesii, and Trametes lactinea—were not previously reported in Korea. Considering that the proportion of unrecorded species is high in the survey area and period as well as the number of samples collected, similar research on adjacent islands may be necessary.

Surimi is refined myofibrillar proteins of fish, which are materials of processed seafood products. However, the health-related outcomes associated with surimi consumption need further investigation. Given the high valued impact of surimi in the functional food industry, the study aims to evaluate its digest with regard to antioxidant potential to understand health benefits raised by surimi consumption. Paralichthys olivaceus surimi digest (POSD) showed a significant DPPH and alkyl radical scavenging activity and protective effects against 2,20-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stressed Vero cells with a significant increasing cell viability and decreasing apoptosis. It also dramatically suppressed the production of reactive oxygen species and lipid peroxidation as well as prevented cell death and down-regulated pro-apoptotic genes at the mRNA levels in AAPH-stimulated zebrafish. This study reports the protective effects against oxidative stressed cells and zebrafish by a strong antioxidant activity of POSD. Therefore, surimi consumption could be a potential benefit in the prevention of oxidative stress-related diseases.

Plants dynamically adapt to changing temperatures to ensure propagation and reproductive success, among which morphogenic responses to warm temperatures have been extensively studied in recent years. As readily inferred from the cyclic co-oscillations of environmental cues in nature, plant thermomorphogenesis is coordinately reshaped by various external conditions. Accumulating evidence supports that internal and developmental cues also contribute to harmonizing thermomorphogenic responses. The external and internal reshaping of thermomorphogenesis is facilitated by versatile temperature sensing and interorgan communication processes, circadian and photoperiodic gating of thermomorphogenic behaviors, and their metabolic coordination. Here, we discuss recent advances in plant thermal responses with focus on the diel and seasonal reshaping of thermomorphogenesis and briefly explore its application to developing climate-smart crops.

Seven species and two varieties belonging to the genus Boehmeria Jacq. (Urticaceae) are known to be distributed in Korea. Among them, B. spicata, B. tricuspis, and B. tricuspis var. unicuspis were subjected to an external morphological study. Among the individuals believed to exhibit variations in the leaf shape, B. gracilis and B. silvestrii were newly recognized. Unlike related taxa, B. gracilis has middle leaves with an elliptic, broadly elliptic, ovate, or broadly depressed ovate shape, a regular and serrulate-dentate margin, and an unlobed and short caudate or cuspidate apex. Boehmeria silvestrii has middle leaves with 5-angled ovate, orbicular ovate or broadly ovate shapes, and 3- or 5-lobed and caudate apices. Therefore, we assigned the corresponding names ‘Top-geo-buk-kko-ri’ and ‘Cham-geo-buk-kko-ri’. Meanwhile, the B. spicata complex (B. gracilis, B. silvestrii, B. spicata, and B. tricuspis var. unicuspis) is very closely related in terms of the morphological characters, whereas B. tricuspis exhibits no relationship. Furthermore, because the scientific name and type specimen of B. tricuspis var. unicuspis (Pul-geo-buk-kko-ri) are problematic, the correct name B. paraspicata Nakai and corresponding holotype are presented. Additionally, lectotypes of B. gracilis and B. silvestrii are newly designated here. A taxonomic treatment, descriptions, a key, photographs, type specimens, and leaf variation images of the B. spicata complex are provided in this study.

We report a novel strategy to offer a high-performance biosensor platform by fabricating an electrically conductive and adhesive electrode composed of polypyrrole (PPy)/polydopamine (PDA) with enzymes (i.e., glucose oxidase (GOx) or lactate oxidase (LOx)) by one-step electrochemical coating. We focused on electrochemical glucose sensing using PDA/PPy and GOx as a model biosensor. PDA/PPy/GOx biosensor was highly sensitive (28 times higher) compared to the PPy/GOx, which appeared to result from enhanced GOx immobilization and efficient signal transduction by PDA/PPy. A selective layer of polyphenol (PPh) on the PDA/PPy/GOx successfully eliminated possible interference. Finally, the GOx biosensor displayed a good sensitivity of 22.15 μ A mM−1 cm-2, a short response time of 5−6 s, a linear range up to 5.0 mM, and a detection limit of 138 μM glucose (R2 = 0.995). Human blood serum tests accurately measured glucose concentration. PPh-layered PDA/PPy/GOx biosensor maintained exceptional stability over 90 days (93.9%). Furthermore, we fabricated a lactate biosensor (PDA/PPy/LOx) by electrochemical PDA/PPy deposition with LOx and demonstrated the significant improvement of a lactate sensing ability compared to PPy/LOx. This facile fabrication strategy involving PDA/PPy and enzymes will serve as an attractive platform for highly sensitive and stable biosensors, such as urate and bilirubin detection.

CRISPR/Cas9-mediated genome editing is an important and versatile technology in modern biological research. Recent advancements include base-editing CRISPR tools that enable targeted nucleotide substitutions using a fusion protein comprising a nickase variant of Cas9 and a base deaminase. Improvements in base editing efficiencies and inheritable of edited loci need to be made to make CRISPR a viable system in plants. Here, we report efficiency of cytosine base editors (CBEs) in Arabidopsis thaliana by applying the strong endogenous RPS5a promoter to drive the expression of nickase Cas9 and either rAPOBEC1 from rat (BE3) or the PmCDA1 activation-induced cytidine deaminase from sea lamprey (AIDv2). Compared with the strong heterologous CaMV35S promoter of viral origin, the RPS5a promoter improved CBE efficiency by 32% points with the number of T1 plants showing over 50% conversion ratio when the LFY gene was targeted. CBE induced nonsense mutations in LFY via C-to-T conversion, which resulted in loss-of-function lfy phenotypes; defects in LFY function were associated with the targeted base substitutions. Our data suggest that optimal promoter choice for CBE expression may affect base-editing efficiencies in plants. The results provide a strategy to optimize low-efficiency base editors and demonstrate their applicability for functional assays and trait development in crop research.

The eradication rate of clarithromycin-based standard triple therapy (STT) for Helicobacter pylori infection has decreased due to clarithromycin resistance (CR). We evaluated the cost-effectiveness of tailored therapy according to CR test results, and compared the results of STT with those of empirical bismuth quadruple therapy (BQT). The prospectively collected data of 490 H. pylori-positive patients with chronic gastritis or peptic ulcer disease were retrospectively analyzed. Among them, 292 patients underwent CR testing using dual-priming oligonucleotide-based polymerase chain reaction. The tailored group (n = 292) consisted of patients treated with STT for 7 days and BQT for 10 days as per their CR test results. The remaining patients were assigned to the empirical group (n = 198) and received BQT for 10 days without a CR test. The eradication rate, adverse events and medical costs associated with H. pylori eradication therapy were investigated. In the tested patients (tailored group), the CR-positive rate was 32.2% (n = 94/292). The eradication rate according to an intention-to-treat analysis was 87.7% in the tailored group and 91.8% in the empirical group (P = 0.124); the respective rates were 94.4% and 97.9% by per-protocol analysis (P = 0.010). The frequency of adverse events was lower in the empirical group than the tailored group (35.1% vs. 52.7%, P

Graphical abstract, Highlights • Aberrant STAT3 activation can promote neoplastic transformation by affecting cellular proliferation, invasion, metastasis, angiogenesis, and anti-apoptosis induction. • Fangchinoline abrogated protein expression levels of STAT3 and upstream signals (JAK1/2 and Src) in different tumor cells. • Fangchinoline inhibited the levels of various tumorigenic markers and promoted marked apoptosis through degradation of PARP and caspase-3. • Fangchinoline attenuated the level of STAT3 and upstream signals and suppressed the level of anti- apoptotic proteins in xenograft mice model., Introduction The development of cancer generally occurs as a result of various deregulated molecular mechanisms affecting the genes that can control normal cellular growth. Signal transducer and activator of transcription 3 (STAT3) pathway, once aberrantly activated can promote carcinogenesis by regulating the transcription of a number of oncogenic genes. Objectives Here, we evaluated the impact of fangchinoline (FCN) to attenuate tumor growth and survival through modulation of oncogenic STAT3 signaling pathway using diverse tumor cell lines and a xenograft mouse model. Methods To evaluate the action of FCN on STAT3 cascade, protein levels were analyzed by Western blot analysis and electrophoretic mobility shift assay (EMSA). Translocation of STAT3 was detected by immunocytochemistry. Thereafter, FCN-induced ROS was measured by GSH/GSSG assay and H2DCF-DA. FCN-induced apoptosis was analyzed using Western blot analysis and flow cytometry for various assays. Finally, anti-cancer effects of FCN in vivo was evaluated in a myeloma model. Results We noted that FCN abrogated protein expression levels of STAT3 and upstream signals (JAK1/2 and Src). In addition, FCN also attenuated DNA binding ability of STAT3 and its translocation into the nucleus. It altered the levels of upstream signaling proteins, increased SHP-1 levels, and induced substantial apoptosis in U266 cells. FCN also promoted an increased production of reactive oxygen species (ROS) and altered GSSG/GSH ratio in tumor cells. Moreover, FCN effectively abrogated tumor progression and STAT3 activation in a preclinical myeloma model. Conclusion Overall, this study suggests that FCN may have a tremendous potential to alter abnormal STAT3 activation and induce cell death in malignant cells along with causing the suppression of pathogenesis and growth of cancer through a pro-oxidant dependent molecular mechanism.

The gaseous phytohormone ethylene plays vital roles in diverse developmental and environmental adaptation processes, such as fruit ripening, seedling establishment, mechanical stress tolerance and submergence escape. It is also known that in the light, ethylene promotes hypocotyl growth by stimulating the expression of PHYTOCHROME INTERACTING FACTOR3 (PIF3) transcription factor, which triggers microtubule reorganization during hypocotyl cell elongation. In particular, ethylene has been implicated in plant responses to warm temperatures in recent years. However, it is currently unclear how ethylene signals are functionally associated with hypocotyl thermomorphogenesis at the molecular level. Here, we show that ETHYLENE-INSENSITIVE3 (EIN3)-mediated ethylene signals attenuate hypocotyl thermomorphogenesis by suppressing auxin response. At warm temperatures, when the activity of the PIF4 thermomorphogenesis promoter is prominently high, the ethylene-activated EIN3 transcription factor directly induces the transcription of ARABIDOPSIS PP2C CLADE D7 (APD7) gene encoding a protein phosphatase that inactivates the plasma membrane (PM) H+-ATPase proton pumps. In conjunction with the promotive role of the PM H+-ATPases in hypocotyl cell elongation, our observations strongly support that the EIN3-directed induction of APD7 gene is linked with the suppression of auxin-induced cell expansion, leading to the reduction in thermomorphogenic hypocotyl growth. Our data demonstrate that APD7 acts as a molecular hub that integrates ethylene and auxin signals into hypocotyl thermomorphogenesis. We propose that the ethylene–auxin signaling crosstalks via the EIN3-APD7 module facilitate the fine-tuning of hypocotyl thermomorphogenesis under natural environments, which often fluctuate in a complex manner.

The anti-inflammatory effect of a fucoidan with a molecular weight of 102.67 kDa isolated from an enzymatic digest of Sargassum fusiforme was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that the fucoidan significantly and dose-dependently inhibited the production of inflammatory molecules, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as improved the viability of LPS-stimulated RAW 264.7 cells. Moreover, the fucoidan suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by regulating the nuclear factor kappa B (NF-κB) pathway in LPS-stimulated RAW 264.7 cells. Furthermore, in vivo test results suggested that the fucoidan remarkably reduced reactive oxygen species (ROS), cell death, and NO levels in LPS-stimulated zebrafish in a dose-dependent manner. Taken together, these results demonstrated that the fucoidan isolated from S. fusiforme possesses strong anti-inflammatory activities in vitro and in vivo, and could prove as an important candidate to be used to develop anti-inflammatory agents in pharmaceutical and cosmeceutical industries.

Background The early diagnosis and treatment of skin and soft tissue infections caused by nontuberculous mycobacteria (NTM) are important, especially as infections with rapidly growing mycobacteria (RGM) are rare and difficult to diagnose and treat. Recently, we identified 22 cases of NTM infections; in this study, we suggest treatment strategies by analyzing the demographic characteristics and treatment progress of these patients. Methods A retrospective study of patients with NTM infections from 2009 to 2019 was conducted. To identify NTM infections, acid-fast bacillus (AFB) staining, Gram staining, polymerase chain reaction (PCR), and cultures of mycobacteria were performed. Empirical treatment with a combination of antibiotics or surgery was performed; species identification and drug susceptibility tests were performed by the Korean National Tuberculosis Association. The final regimen was determined after obtaining the test results. Results The mean incubation time of NTM was 4.32±2.88 weeks. RGM were detected in mycobacterial cultures in 21 of the 22 NTM patients. The results of AFB staining were negative in all patients, although PCR was positive for NTM in one patient. Fourteen patients were hospitalized for treatment with intravenous antibiotics and surgery. Treatment with a combined regimen of oral antibiotics was maintained for a mean of 5.41±1.85 months. Conclusions The unusual clinical manifestations of skin and soft tissue infections caused by NTM make them difficult to diagnose. Suspicion of NTM based on clinical presentation and a detailed examination should be followed by proper treatment involving multiple antibiotics and surgery in these patients.

The gastrointestinal tract in the adult Drosophila serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to UAS-GFP to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.

Vacuolar ATPase (v-ATPase) is the main proton pump that acidifies vesicles such as lysosomes. Disruption in the lysosomal localization of v-ATPase leads to lysosomal dysfunction, thus contributing to the pathogenesis of lysosomal storage disorders and neurodegenerative diseases such as Alzheimer's disease. Recent studies showed that increases in cyclic AMP (cAMP) levels acidify lysosomes and consequently enhance autophagy flux. Although the upregulation of v-ATPase function may be the key mechanism underlying the cAMP-mediated lysosomal acidification, it is unknown whether a mechanism independent of v-ATPase may be contributing to this phenomenon. In the present study, we modeled v-ATPase dysfunction in brain cells by blocking lysosomal acidification in cortical astrocytes through treatment with bafilomycin A1, a selective v-ATPase inhibitor. We observed that cAMP reversed the pH changes via the activation of protein kinase A; interestingly, cAMP also increased autophagy flux even in the presence of bafilomycin A1, suggesting the presence of an alternative route of proton entry. Notably, pharmacological inhibitors and siRNAs of H+ /K+ -ATPase markedly shifted the lysosomal pH toward more alkaline values in bafilomycin A1/cAMP-treated astrocytes, suggesting that H+ /K+ -ATPase may be the alternative route of proton entry for lysosomal acidification. Furthermore, the cAMP-mediated reversal of lysosomal pH was nullified in the absence of ZnT3 that interacts with H+ /K+ -ATPase. Our results suggest that the H+ /K+ -ATPase/ZnT3 complex is recruited to lysosomes in a cAMP-dependent manner and functions as an alternative proton pump for lysosomes when the v-ATPase function is downregulated, thus providing insight into the potential development of a new class of lysosome-targeted therapeutics in neurodegenerative diseases.

Background While aging causes muscle weakness, type 2 diabetes mellitus (T2DM) is also considered a high-risk factor for the induction of skeletal muscle weakness. Previous studies have reported increased collagen content in insulin-resistant skeletal muscles. Here, we studied the mechanical properties of aged skeletal muscle in subjects with T2DM to investigate whether aged skeletal muscles with T2DM induce higher passive tension due to the abundance of extracellular matrix (ECM) inside or outside of the muscle fibers. Methods Samples from the gluteus maximus muscles of older adults with diabetes (T2DM) and non-diabetic (non-DM) older adults who underwent elective orthopedic surgery were collected. Permeabilized single muscle fibers from these samples were used to identify their mechanical properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to quantify titin and fiber type distributions in these samples. Results We confirmed a significant predominance of type I fiber ratio in both T2DM and non-DM aged muscles. While the average cross-sectional area and maximal active tension of the single fibers were smaller in the T2DM group than those in the non-DM group, the difference was not statistically significant. T2DM subjects showed significantly greater passive tension and lower titin-/ECM-based passive tension ratios than those in non-DM subjects, which indicated that more ECM but less titin contributed to the total passive tension. Conclusion Based on our findings, we concluded that T2DM may cause increased passive stiffness of single skeletal muscle fibers in older adults because of an excessive accumulation of ECM in and around single muscle fibers due to increased insulin resistance.

Background Crossover second toe is often presented in moderate to severe hallux valgus. However, its clinical impact on the postoperative outcome of hallux valgus is still unknown. Methods Thirty-five patients who had moderate to severe hallux valgus with crossover second toe were matched with 35 controls who did not have crossover second toe, according to preoperative hallux valgus angle and first-second intermetatarsal angle. Radiological parameters, Foot Function Index (FFI), and Visual Analog Scale (VAS) were assessed as postoperative outcomes at 3, 6, and 12 months after surgery. Results At 3 months, the FFI in the crossover second toe group was lower than in the control group (p = 0.001), while other outcomes were similar. On the other hand, there were no significant differences between the groups at 6 and 12 months, in terms of radiological parameters, FFI, and VAS. Conclusions Patients who had moderate to severe hallux valgus with crossover second toe were at risk for slow functional recovery after surgical treatment in the short term, but, in the long-term, there was no difference in overall postoperative outcomes in patients with and without crossover second toe. Level of Evidence Level III, retrospective comparative study.

Cytosolic Ca2+ levels ([Ca2+]c) change dynamically in response to inducers, repressors, and physiological conditions, and aberrant [Ca2+]c concentration regulation is associated with cancer, heart failure, and diabetes. Therefore, [Ca2+]c is considered as a good indicator of physiological and pathological cellular responses, and is a crucial biomarker for drug discovery. A genetically encoded calcium indicator (GECI) was recently developed to measure [Ca2+]c in single cells and animal models. GECI have some advantages over chemically synthesized indicators, although they also have some drawbacks such as poor signal-to-noise ratio (SNR), low positive signal, delayed response, artifactual responses due to protein overexpression, and expensive detection equipment. Here, we developed an indicator based on interactions between Ca2+-loaded calmodulin and target proteins, and generated an innovative GECI sensor using split nano-luciferase (Nluc) fragments to detect changes in [Ca2+]c. Stimulation-dependent luciferase activities were optimized by combining large and small subunits of Nluc binary technology (NanoBiT, LgBiT:SmBiT) fusion proteins and regulating the receptor expression levels. We constructed the binary [Ca2+]c sensors using a multicistronic expression system in a single vector linked via the internal ribosome entry site (IRES), and examined the detection efficiencies. Promoter optimization studies indicated that promoter-dependent protein expression levels were crucial to optimize SNR and sensitivity. This novel [Ca2+]c assay has high SNR and sensitivity, is easy to use, suitable for high-throughput assays, and may be useful to detect [Ca2+]c in single cells and animal models.

BACKGROUND AND AIMS This prospective observational study aimed to evaluate the best serum and urine markers to assess predictability for the prognosis of patients with decompensated cirrhosis. METHODS Serum creatinine and cystatin C (CysC), and urinary N-acetyl-beta-D glucosaminidase (uNAG) and neutrophil gelatinase-associated lipocalin (uNGAL) levels were measured from hospitalized patients with decompensated cirrhosis. RESULTS In total, 328 patients (mean age, 57.2 ± 12.0 years; 237 men) with decompensated cirrhosis were included. Alcoholic liver disease was the most frequent underlying liver disease (68.0%). Acute kidney injury (AKI) was concomitantly present in 41 patients (12.5%) at baseline. INR, serum creatinine and CysC levels, and uNAG and uNGAL levels were significantly higher in patients with AKI. During hospitalization, AKI had progressed in 37 patients (11.3%). In 287 patients without AKI, the incidence of AKI at 3, 6, 9 and 12 months was 15.4%, 22.2%, 28.6% and 32.5% respectively. On multivariate analysis, serum CysC and uNAG levels were independent predictors of AKI, and their optimal cut-off values were 1.055 mg/L and 23.1 U/g urinary Cr respectively. When patients were classified into three groups with these cut-off values of serum CysC and uNAG levels (group 1, both low; group 2, one of two high; and group 3, both high), progression of AKI during hospitalization (P = .001), incidence of AKI in patients without AKI at baseline (P = .001) and mortality rate (P

Hepatic artery pseudoaneurysm is a rare but potentially life-threatening condition that usually occurs after trauma. Early recognition and prompt management are essential for preventing catastrophic consequences, such as hemoperitoneum. We report a rare case of liver abscess caused by Klebsiella oxytoca resulting in hepatic artery pseudoaneurysm without iatrogenic injury. The unique feature of the present case is that the abscess cavity itself became a pseudoaneurysm as a result of fistula formation with the hepatic artery. Vascular complications should be considered in patients with unfavorable clinical course even in the absence of iatrogenic injury. Endovascular treatment is safe and effective.

The various functional properties of chitosan have been investigated for use in biomedical applications. Indeed, chitosan or its derivatives have shown anti-inflammatory effect by regulating a range of cytokines, chemokines or growth factors. In the present study, we prepared water-soluble chitosan oligosaccharide (AS-WSC) by the hydrolysis of high molecular weight water-soluble chitosan (HMW-WSC) and examined its anti-inflammatory effect on LPS-stimulated human monocytic THP-1 cells. Our results revealed that LPS-induced NF-κB activity of THP-1 cells was significantly suppressed by treatment with 0.02% AS-WSC. In addition, 0.02% AS-WSC treatment down-regulated the expression of Toll-like receptor 4 and inflammatory cytokines, such as IL-1β and TNF-α, but had no effect on IL-10 and IL-4 expression in LPS-stimulated THP-1 cells. Our results suggest that 0.02% AS-WSC can be considered as a promising anti-inflammatory agent.

Canine parvovirus (CPV) remains a leading infectious cause of death in canines, especially in young puppies. Though vaccination is being carried out regularly, immunization failures occur, and puppies may be exposed to infection. Virus-like particles (VLPs) act like a subunit vaccine, mimicking the structure of authentic viruses. Therefore, VLPs have the potential to be used as vaccine candidates. Since Viral Protein 2 (VP2), a major structural protein of CPV, is the crucial antigen for CPV, the purpose of this study was to produce a recombinant VP2 of new canine parvovirus-2a using the baculovirus expression system in SF9 insect cells. The results revealed that recombinant VP2 assembles to form VLPs with antigenic properties similar to those of natural CPV, the recombinant VLP can produce a hemagglutination assay (HA) titer (1:2¹⁰) in SF9 cells. Expression of the recombinant 6-His-tagged VP2 in SF9 cells was confirmed by western blotting. These findings suggest that the recombinant VP2 expressed in this study could be used as an efficient subunit vaccine against CPV infection.

According to relevant literature, the consumption of seahorses has been used to increase male functions by improving blood flow and decreasing blood pressure. Thus, it was theorized that seahorses may also be effective against hypertension. Herein, vasodilation caused via the inhibitory effect of angiotensin-converting enzymes (ACEs) in peptides was elucidated by studying the seahorses (Hippocampus abdominalis) farmed at Jeju in South Korea. Hydrolysate was prepared using the Protamex (SHP) enzyme. The ultrafiltration system was adopted to separate certain fractions from SHP according to different molecular weights (SHP-I, MW > 10 kDa; SHP-II, MW = 5−10 kDa; SHP-III, MW

Due to their target specificity and low-toxicity, insect growth regulators (IGRs) are regarded as promising alternatives to chemical insecticides. In this study, farnesol and farnesyl acetate exhibited juvenile hormone (JH)-based IGR activities. While farnesyl acetate showed JH agonist (JHA) activity in concentration-dependent manner, farnesol was identified as JH antagonist (JHAN) by interfering pyriproxyfen-mediated binding JH receptor complex. Both compounds showed mosquito larvicidal activities and caused retardation of ovarian growth of female Aedes albopictus by modulating the formation of JH receptor complex, expression of JH-inducible genes, and thereby disrupting JH-based endocrine regulations. These results suggested that farnesol and farnesyl acetate could be applicable for investigating underlying mechanisms of JH-regulated insect physiologies as well as developing novel eco-friendly insecticides.

This study aimed to investigate the distribution and epidemiological relatedness of methicillin-resistant Staphylococcus aureus (MRSA) isolates from companion dogs, owners, and residential environments of 72 households. Sampling was performed twice from January to June 2018 and a total of 2,592 specimens were collected. The specimens collected from each household were streaked on CHROM agar S. aureus and the colonies grown on the medium were further identified using a mass spectrometry microbial identification system. Antimicrobial susceptibility testing, Panton-Valentine-Leukocidin (PVL) gene PCR, staphylococcal cassette chromosome mec (SCCmec) typing, Staphylococcus aureus Protein A (spa) typing, pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing (MLST) were conducted to evaluate the phenotypic and genotypic characteristics of the MRSA isolates. A total of 65 S. aureus strains (2.5%) were isolated and 49 (1.9%) of 65 strains were MRSA displaying cefoxitin-resistance with mecA carriage. MRSA strains were isolated from dogs (n=6, 9.2%), owners (n=27, 41.5%), and residential environments (n=16, 24.6%), respectively. Overall prevalence of non-duplicated MRSA was 16.7% (12/72 households) at household level. ST72-SCCmec IVc MRSA clones predominantly appeared in MRSA-positive families. Furthermore, PFGE analyses showed that ST72-SCCmec IVc-t324 is shared between dog owners and dogs. To our knowledge, this is the first study to report the sharing of ST72 MRSA between dogs and their owners.

Screening esophagogastroduodenoscopy of a 65-year-old man revealed a 4.7-cm polypoid in the gastric high body. Clinical and laboratory findings, including serum gastrin level (460 pg/mL) and biopsy findings, were consistent with a diagnosis of type I neuroendocrine tumor (NET). Histologically, the mass consisted of dilated tortuous glands at the surface and grade 1 NET in deeper tissue. Some hyperplastic glands exhibited a transition to adenocarcinoma, which invaded the NET, simulating a "tumor in tumor" appearance. Next-generation sequencing revealed that the adenocarcinoma component harbored a TP53 mutation, whereas the NET component showed no pathogenic mutation. To our knowledge, this unusual collision of adenocarcinoma and NET within a single gastric hyperplastic polyp has not been previously described. This case suggests that large gastric hyperplastic polyps should be carefully examined because of the possibility of underlying NET and malignant transformation of surface epithelium.

Citrus peel has been used as a Traditional medicine in Asia to treat coughs, asthma and bronchial disorders. Therefore, the anti-inflammatory effects of 3,5,6,7,3′,4′-hexamethoxyflavone (quercetogetin, QUE) isolated from Citrus unshiu peel were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The results showed that QUE repressed the production of prostaglandin E2 and nitric oxide by suppressing LPS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase. It also suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α cytokines, and decreased the nuclear translocation of NF-κB by interrupting the phosphorylation of NF-κB inhibitor α in macrophage cells. Based on the finding that QUE inhibited the phosphorylation of ERK protein expression in LPS-induced RAW264.7 cells, it was confirmed that inhibition of inflammatory responses by QUE was mediated via the ERK pathway. Therefore, this study suggests that QUE has strong anti-inflammatory effects, making it a promising compound for use as a therapeutic agent in treating inflammatory lung diseases, such as emphysema.

The His723Arg (H723R) mutation in SLC26A4, encoding pendrin, is the most prevalent mutation in East Asia, resulting in DFNB4, an autosomal recessive type of genetic hearing loss. Although the main pathological mechanism of H723R was identified as a protein-folding defect in pendrin, there is still no curative treatment for associated hearing loss. Here, we show that H723R-pendrin expression and activity are rescued by activation of the chaperonin DNAJC14. In vitro, DNAJC14 was activated via Japanese encephalitis virus (JEV) inoculation, and toxin-attenuated JEV rescued the surface expression and anion exchange activity of H723R-pendrin. Human H723R-pendrin transgenic mice (hH723R Tg) were established in a mouse slc26a4 knockout background, in which only hH723R-pendrin was expressed in the inner ear (Pax2-Cre dependent) to mimic human DFNB4 pathology. Crossing hH723R Tg with DNAJC14-overexpressing mice resulted in reduced cochlear hydrops and more preserved outer hair cells in the cochlea compared to those in hH723R Tg mice. Furthermore, the stria vascularis and spiral ligament were thicker and KCNJ10 expression was increased with DNAJC14 overexpression; however, hearing function and enlarged endolymphatic hydrops were not recovered. These results indicate that DNAJC14 overexpression ameliorates the cochlear degeneration caused by misfolded pendrin and might be a potential therapeutic target for DFNB4.

High pharmacokinetic variability of voriconazole is mainly explained by CYP2C19 phenotype, but there are still unknown factors affecting the variability. In this study, the effect of solute carrier organic anion transporter family member 2B1 (SLCO2B1) genotype on the pharmacokinetics (PKs) of voriconazole was evaluated in 12 healthy CYP2C19 poor metabolizers after a single administration of voriconazole 200 mg intravenously and orally. In addition, the influence of CYP3A4 enzyme activity was also explored. The oral absorption of voriconazole was decreased and delayed in the subjects with the SLCO2B1 c.*396T>C variant compared to the subjects with wild type. However, the CYP3A activity markers measured in this study did not show significant association with metabolism of voriconazole. The results suggest that the SLCO2B1 c.*396T>C may be associated with the decreased function of intestinal OATP2B1, and it could contribute to interindividual PK variability of voriconazole.

Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin's suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin's suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin's suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.

Brown adipocytes, which contain abundant mitochondria, use stored energy as fuel during a process named nonshivering thermogenesis. Thus, the pharmacological activation of thermogenesis in brown adipose tissue (BAT) has become a promising target for treating obesity. We investigated the effect of fruit of Hovenial dulcis Thunb. (FHD), a frequently used herbal treatment for liver diseases, on thermogenesis and its mechanism using primary cultured brown adipocytes and BAT of high-fat-diet (HFD)-induced obese mice. Thermogenesis-related factors including UCP1 and PGC1α increased with FHD treatment. FHD also increased mitochondrial biogenesis and activation factors such as nuclear respiratory factor (NRF)1 and oxidative phosphorylation (OXPHOS) complex. Furthermore, FHD increased the intercellular nicotinamide adenine dinucleotide (NAD+) level and sirtuin 1 (SIRT1) activity, which may be responsible for the activation of the thermogenic reaction. Overall, our results suggest that FHD can be a novel option for obesity treatment due to its thermogenic action through mitochondrial biogenesis and activation.

Rice (Oryza sativa) is one of the world's most important food crops, and is comprised largely of japonica and indica subspecies. Here, we reconstruct the history of rice dispersal in Asia using whole-genome sequences of more than 1,400 landraces, coupled with geographic, environmental, archaeobotanical and paleoclimate data. Originating around 9,000 yr ago in the Yangtze Valley, rice diversified into temperate and tropical japonica rice during a global cooling event about 4,200 yr ago. Soon after, tropical japonica rice reached Southeast Asia, where it rapidly diversified, starting about 2,500 yr BP. The history of indica rice dispersal appears more complicated, moving into China around 2,000 yr BP. We also identify extrinsic factors that influence genome diversity, with temperature being a leading abiotic factor. Reconstructing the dispersal history of rice and its climatic correlates may help identify genetic adaptations associated with the spread of a key domesticated species.

The subgranular zone of the dentate gyrus is a subregion of the hippocampus that has two uniquely defining features; it is one of the most active sites of adult neurogenesis as well as the location where the highest concentrations of synaptic zinc are found, the mossy fiber terminals. Therefore, we sought to investigate the idea that vesicular zinc plays a role as a modulator of hippocampal adult neurogenesis. Here, we used ZnT3 −/− mice, which are depleted of synaptic‐vesicle zinc, to test the effect of targeted deletion of this transporter on adult neurogenesis. We found that this manipulation reduced progenitor cell turnover as well as led to a marked defect in the maturation of newborn cells that survive in the DG toward a neuronal phenotype. We also investigated the effects of zinc (ZnCl2), n‐acetyl cysteine (NAC), and ZnCl2 plus 2NAC (ZN) supplement on adult hippocampal neurogenesis. Compared with ZnCl2 or NAC, administration of ZN resulted in an increase in proliferation of progenitor cells and neuroblast. ZN also rescued the ZnT3 loss‐associated reduction of neurogenesis via elevation of insulin‐like growth factor‐1 and ERK/CREB activation. Together, these findings reveal that ZnT3 plays a highly important role in maintaining adult hippocampal neurogenesis and supplementation by ZN has a beneficial effect on hippocampal neurogenesis, as well as providing a therapeutic target for enhanced neuroprotection and repair after injury as demonstrated by its ability to prevent aging‐dependent cognitive decline in ZnT3 −/− mice. Therefore, the present study suggests that ZnT3 and vesicular zinc are essential for adult hippocampal neurogenesis., This study utilized ZnT3 −/− mice with a genetic loss‐of‐function approach to investigate the consequences of vesicular zinc depletion in adult hippocampal neurogenesis. We found that ZnT3 −/− mice displayed reduced hippocampal neurogenesis under physiological conditions even at 3 months of age. We also found that administration of ZnCl2 plus 2NAC (ZN) not only reversed the ZnT3 loss‐associated reduction of neurogenesis, but also improved aging‐dependent cognitive decline in ZnT3 −/− mice.

Macrofungi play important roles in forest ecology as wood decayers, symbionts, and pathogens of living trees. For the effective forest management, it is imperative to have a comprehensive overview of macrofungi diversity in specific areas. As a part of the National Institute of Biological Resources projects for discovering indigenous fungi in Korea, we collected macrofungi in Gayasan National Park from 2017 to 2018. These specimens were identified based on morphological characteristics and sequence analysis of internal transcribed spacer (ITS) or the nuclear large subunit rRNA (LSU) region. We discovered 17 macrofungi new to Korea: Butyrea japonica, Ceriporia nanlingensis, Coltricia weii, Coltriciella subglobosa, Crepidotus crocophyllus, Cylindrobasidium laeve, Fulvoderma scaurum, Laetiporus cremeiporus, Lentinellus castoreus, Leucogyrophana mollusca, Marasmius insolitus, Nidularia deformis, Phaeophlebiopsis peniophoroides, Phanerochaete angustocystidiata, Phlebiopsis pilatii, Postia coeruleivirens, and Tengioboletus fujianensis. We described their detailed morphological characteristics.