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  • 1
    Online Resource
    Online Resource
    Antifungal Activity of 1,4-Dialkoxynaphthalen-2-Acyl Imidazolium Salts by Inducing Apoptosis of Pathogenic Candida spp.
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 3 ( 2021-02-27), p. 312-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 3 ( 2021-02-27), p. 312-
    Abstract: Even though Candida spp. are staying commonly on human skin, it is also an opportunistic pathogenic fungus that can cause candidiasis. The emergence of resistant Candida strains and the toxicity of antifungal agents have encouraged the development of new classes of potent antifungal agents. Novel naphthalen-2-acyl imidazolium salts (NAIMSs), especially 1,4-dialkoxy-NAIMS from 1,4-dihydroxynaphthalene, were prepared and evaluated for antifungal activity. Those derivatives showed prominent anti-Candida activity with a minimum inhibitory concentration (MIC) of 3.125 to 6.26 μg/mL in 24 h based on microdilution antifungal susceptibility test. Among the tested compounds, NAIMS 7c showed strongest antifungal activity with 3.125 μg/mL MIC value compared with miconazole which showed 12.5 μg/mL MIC value against Candida spp., and more importantly 〉 100 μg/mL MIC value against C. auris. The production of reactive oxygen species (ROS) was increased and JC-1 staining showed the loss of mitochondrial membrane potential in C. albicans by treatment with NAIMS 7c. The increased release of ultraviolet (UV) absorbing materials suggested that NAIMS 7c could cause cell busting. The expression of apoptosis-related genes was induced in C. albicans by NAIMS 7c treatment. Taken together, the synthetic NAIMSs are of high interest as novel antifungal agents given further in vivo examination.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13030312
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
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  • 2
    Online Resource
    Online Resource
    Utilizing Red Spotted Apollo Butterfly Transcriptome to Identify Antimicrobial Peptide Candidates against Porphyromonas gingivalis
    MDPI AG ; 2021
    In:  Insects Vol. 12, No. 5 ( 2021-05-18), p. 466-
    Details
    In: Insects, MDPI AG, Vol. 12, No. 5 ( 2021-05-18), p. 466-
    Abstract: Classical antibiotics are the foremost treatment strategy against microbial infections. Overuse of this has led to the evolution of antimicrobial resistance. Antimicrobial peptides (AMPs) are natural defense elements present across many species including humans, insects, bacteria, and plants. Insect AMPs are our area of interest, because of their stronger abilities in host defense. We have deciphered AMPs from an endangered species Parnassius bremeri, commonly known as the red spotted apollo butterfly. It belongs to the second largest insect order Lepidoptera, comprised of butterflies and moths, and lives in the high altitudes of Russia, China, and Korea. We aimed at identifying the AMPs from the larvae stages. The rationale of choosing this stage is that the P. bremeri larvae development occurs at extremely low temperature conditions, which might serve as external stimuli for AMP production. RNA was isolated from larvae (L1 to L5) instar stages and subjected to next generation sequencing. The transcriptomes obtained were curated in in-silico pipelines. The peptides obtained were screened for requisite AMP physicochemical properties and in vitro antimicrobial activity. With the sequential screening and validation, we obtained fifteen candidate AMPs. One peptide TPS–032 showed promising antimicrobial activity against Porphyromonas gingivalis, a primary causative organism of periodontitis.
    Type of Medium: Online Resource
    ISSN: 2075-4450
    URL: Article
    DOI: 10.3390/insects12050466
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662247-6
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  • 3
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    Online Resource
    Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 2 ( 2021-01-18), p. 336-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 2 ( 2021-01-18), p. 336-
    Abstract: The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13020336
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Methyl P-Coumarate Ameliorates the Inflammatory Response in Activated-Airway Epithelial Cells and Mice with Allergic Asthma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 23 ( 2022-11-28), p. 14909-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 23 ( 2022-11-28), p. 14909-
    Abstract: Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1β, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232314909
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Highly Efficient Bioconversion of trans-Resveratrol to δ-Viniferin Using Conditioned Medium of Grapevine Callus Suspension Cultures
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 8 ( 2022-04-15), p. 4403-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 8 ( 2022-04-15), p. 4403-
    Abstract: δ-Viniferin is a resveratrol dimer that possesses potent antioxidant properties and has attracted attention as an ingredient for cosmetic and nutraceutical products. Enzymatic bioconversion and plant callus and cell suspension cultures can be used to produce stilbenes such as resveratrol and viniferin. Here, δ-viniferin was produced by bioconversion from trans-resveratrol using conditioned medium (CM) of grapevine (Vitis labruscana) callus suspension cultures. The CM converted trans-resveratrol to δ-viniferin immediately after addition of hydrogen peroxide (H2O2). Peroxidase activity and bioconversion efficiency in CM increased with increasing culture time. Optimized δ-viniferin production conditions were determined regarding H2O2 concentration, incubation time, temperature, and pH. Maximum bioconversion efficiency reached 64% under the optimized conditions (pH 6.0, 60 °C, 30 min incubation time, 6.8 mM H2O2). In addition, in vitro bioconversion of trans-resveratrol was investigated using CM of different callus suspension cultures, showing that addition of trans-resveratrol and H2O2 to the CM led to production of δ-viniferin via extracellular peroxidase-mediated oxidative coupling of two molecules of trans-resveratrol. We thus propose a simple and low-cost method of δ-viniferin production from trans-resveratrol using CM of plant callus suspension cultures, which may constitute an alternative approach for in vitro bioconversion of valuable molecules.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23084403
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 6
    Online Resource
    Online Resource
    Configuration of Non-Pumping Reactive Wells Considering Minimum Well Spacing
    MDPI AG ; 2021
    In:  Applied Sciences Vol. 11, No. 23 ( 2021-12-02), p. 11408-
    Details
    In: Applied Sciences, MDPI AG, Vol. 11, No. 23 ( 2021-12-02), p. 11408-
    Abstract: A non-pumping reactive well (NPRW) is a subsurface structure that prevents contaminant spread using many non-pumping wells containing reactive media. For the construction of an effective NPRW, a sufficiently small spacing between wells is an important design factor to prevent contaminant leakage. However, close well construction is not recommended because of concerns about the decreased stability of adjacent wells under field conditions. In this research, we proposed a sawtooth array of NPRW as a practical configuration to minimize well spacing while meeting stability requirements in the field. To evaluate the performance of the novel NPRW configurations, a numerical modeling was conducted considering different well diameters and well spacings and their performance was compared taking into account the number of wells and the mass of the reactive material. The comparison results showed that the sawtooth configuration was more practical than a line of wells. The performance curve of NPRWs with the saw-toothed configuration was constructed from the relationship between the contaminant removal and configuration components (diameter and spacing of the well). This can be used to predict the contaminant removal performance of NPRWs with a sawtooth array.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app112311408
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704225-X
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  • 7
    Online Resource
    Online Resource
    Early Detection of Bacteraemia Using Ten Clinical Variables with an Artificial Neural Network Approach
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 10 ( 2019-10-02), p. 1592-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 10 ( 2019-10-02), p. 1592-
    Abstract: An adequate model for predicting bacteraemia has not yet been developed. This study aimed to evaluate the performance of an artificial neural network (ANN)-based prediction model in comparison with previous statistical models. The performance of multi-layer perceptron (MLP), a representative ANN model, was verified via comparison with a non-neural network model. A total of 1260 bacteraemia episodes were identified in 13,402 patients. In MLP with 128 hidden layer nodes, the area under the receiver operating characteristic curve (AUC) of the prediction performance was 0.729 (95% confidence interval [CI]; 0.712–0.728), while in MLP with 256 hidden layer nodes, it was 0.727 (95% CI; 0.713–0.727). In a conventional Bayesian statistical method, the AUC was 0.7. The aforementioned two MLP models exhibited the highest sensitivity (0.810). The ranking of clinical variables was used to describe the influential power of the prediction. Serum alkaline phosphatase was one of the most influential clinical variables, and one-out search was the best ranking method for measuring the influence of the clinical variables. Furthermore, adding variables beyond the 10 top-ranking ones did not significantly affect the prediction of bacteraemia. The ANN model is not inferior to conventional statistical approaches. Bacteraemia can be predicted using only the top 10 clinical variables determined by a ranking method, and the model can be used in clinical practice by applying real-time monitoring.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8101592
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Online Resource
    Clinical Features, Gene Alterations, and Outcomes in Prefibrotic and Overt Primary and Secondary Myelofibrotic Patients
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 18 ( 2022-09-16), p. 4485-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 18 ( 2022-09-16), p. 4485-
    Abstract: The Philadelphia-negative myeloproliferative neoplasms (MPNs) are divided in three major groups: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 WHO classification incorporates also prefibrotic PMF (pre-PMF) and overt PMF. This study aimed to discriminate the clinical features, genetic alterations, and outcomes in patients with prefibrotic, overt PMF, and secondary MF (SMF). This study included 229 patients with diagnosed myelofibrosis (MF). Among 229 patients, 67 (29%), 122 (53%), and 40 (18%) were confirmed as SMF, overt PMF, and pre-PMF, respectively. The JAK2 V617F mutation was differentially distributed in SMF and PMF, contradictory to CALR and MPL mutations. Regarding nondriver mutations, the occurrence of ASXL1 mutations differed between PMF and SMF or pre-PMF. The three-year overall survival was 91.5%, 85.3%, and 94.8% in SMF, overt PMF, and pre-PMF groups. Various scoring systems could discriminate the overall survival in PMF but not in SMF and pre-PMF. Still, clinical features including anemia and thrombocytopenia were poor prognostic factors throughout the myelofibrosis, whereas mutations contributed differently. Molecular grouping by wild-type SF3B1 and SRSF2/RUNX1/U2AF1/ASXL1/TP53 mutations showed inferior progression-free survival (PFS) in PMF, SMF, and pre-PMF. We determined the clinical and genetic features related to poor prognosis in myelofibrosis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14184485
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    Comprehensive Design of DC Shipboard Power Systems for Pure Electric Propulsion Ship Based on Battery Energy Storage System
    MDPI AG ; 2021
    In:  Energies Vol. 14, No. 17 ( 2021-08-25), p. 5264-
    Details
    In: Energies, MDPI AG, Vol. 14, No. 17 ( 2021-08-25), p. 5264-
    Abstract: With the strengthening of international environmental regulations, many studies on the integrated electric propulsion systems applicable to eco-friendly ship are being conducted. However, few studies have been performed to establish a guide line for the overall pure electric propulsion ship design. Therefore, this paper introduces the comprehensive design of DC shipboard power system for pure electric propulsion ship based on battery energy storage system (BESS). To design and configure the pure electric propulsion ship, 2 MW propulsion car ferry was assumed and adopted to be the target vessel in this paper. In order to design the overall system, a series of design processes, such as the decision of the ship operation profile, BESS capacity selection, configuration of the power conversion systems for propulsion, battery charging/discharging procedures, classification of system operation modes, and analysis of the efficiency, were considered. The proposed efficient design and analysis of the pure electric propulsion ship was qualitatively and quantitatively validated by MATLAB Simulink tool. The methodology presented in this paper can help design real ships before the system commissioning.
    Type of Medium: Online Resource
    ISSN: 1996-1073
    URL: Article
    DOI: 10.3390/en14175264
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2437446-5
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  • 10
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    Depth of Response to Intensive Chemotherapy Has Significant Prognostic Value among Acute Myeloid Leukemia (AML) Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation with Intermediate or Adverse Risk at Diagnosis Compared to At-Risk Group According to European Leukemia Net 2017 Risk Stratification
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 13 ( 2022-06-29), p. 3199-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 13 ( 2022-06-29), p. 3199-
    Abstract: We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n = 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p 〈 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14133199
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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