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    Antioxidant and antimicrobial activities of lignin-derived products from all steam-exploded palm oil mill lignocellulosic biomass waste

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    Background Steam explosion pretreatment has been proven to be an effective treatment for breaking down the recalcitrant character of lignin–carbohydrate complexes (LCC) in lignocellulosic biomass. This study investigated the production of lignin-derived products from steam-exploded palm oil mill lignocellulosic biomass waste (POMLBW), that is, empty fruit bunches (EFB), kernel shells (KS), and kernel fibers (KF), also known as mesocarp fibers. Steam explosions cause lignin depolymerization, which forms various polyphenols. The low average molecular weight of the steam-exploded lignin-derived products and their antioxidant activities could potentially enhance their antimicrobial activities. Methods POMLBW was steam-exploded with various degrees of severity factors (R0: 4.03, 4.91, 5.12, 5.35, and 5.65). Steam-exploded POMLBW produces lignin-derived products such as low-molecular-weight lignin (LML) and water-soluble lignin (WSL). Antioxidant activity was evaluated using 0.5 mM 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Polyphenol content was evaluated using the Folin–Ciocalteu method. The antimicrobial activity was evaluated using an agar diffusion assay with Gram-positive and Gram-negative bacteria, and the thermal characteristics were evaluated using differential scanning calorimetry and thermogravimetric analysis. Results WSL and LML resulted in high radical scavenging activity (RSA) of approximately 95% and 80%, with 0.25 g/L and 0.5 g/L of EC50, where the polyphenol amount was 242–448 mg/g (catechin eq.) and 20–117 mg/g (catechin eq.) under all LML and WSL conditions, respectively. The steam-exploded POMLBW had an average molecular weight of 1589–2832 Da, and this condition, including high RSA and polyphenol amounts, was responsible for the high antimicrobial activities of LML against both Gram-positive (Salmonella enterica, Pseudomonas aeruginosa, and Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Additionally, the thermal properties investigations revealed that the glass transition temperature was 80–90 °C (Tg), the melting temperature (Tm) was 338–362 °C, and the start temperature was 101–128 °C at the beginning of mass loss. Conclusions These results show that the lignin-derived product from steam-exploded POMLBW has the potential for antioxidant (LML and WSL) and antimicrobial (LML) applications with good thermal resistance.journal articl

    Epoxide Ring-Opening Reactions for Abundant Production of Mugineic Acids and Nicotianamine Probes

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    A succinct synthetic approach to mugineic acids and 2’-hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring-opening reactions to form two C-N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2’-hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2’-hydroxy group. The dansyl-labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA-probe through these transporters.journal articl

    LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Ameliorates Endothelial Dysfunction in Diabetic C57BL/6 Mice

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    Aims: LCZ696 (sacubitril/valsartan) exerts cardioprotective effects. Recent studies have suggested that it improves the endothelial function; however, the underlying mechanisms have not been thoroughly investigated. We investigated whether LCZ696 ameliorates diabetes-induced endothelial dysfunction. Methods: Diabetes was induced using streptozotocin in 8-week-old male C57BL/6 mice. Diabetic mice were randomly assigned to receive LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day), or a vehicle for three weeks. The endothelium-dependent and endothelium-independent vascular responses of the aortic segments were determined based on the response to acetylcholine and sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVEC) and aortic segments obtained from C57BL/6 mice were used to perform in vitro and ex vivo experiments, respectively. Results: LCZ696 and valsartan reduced the blood pressure in diabetic mice (P<0.05). The administration of LCZ696 (P<0.001) and valsartan (P<0.01) ameliorated endothelium-dependent vascular relaxation, but not endothelium-independent vascular relaxation, under diabetic conditions. LCZ696, but not valsartan, increased eNOSSer1177 (P=0.06) and Akt (P<0.05) phosphorylation in the aorta. In HUVEC, methylglyoxal (MGO), a major precursor of advanced glycation end products, decreased eNOSSer1177 phosphorylation (P<0.05) and increased eNOSThr495 phosphorylation (P<0.001). However, atrial natriuretic peptide (ANP) reversed these effects. ANP also ameliorated the MGO-induced impairment of endothelium-dependent vascular relaxation in the aortic segments (P<0.05), although L-NAME completely blocked this effect (P<0.001). Conclusion: LCZ696 ameliorated diabetes-induced endothelial dysfunction by increasing the bioavailability of ANP. Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.journal articl

    Essence of Diagnosis and Management of Sleep Bruxism

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    It is common knowledge for dentists that sleep bruxism can produce destructive symptoms in the stomatognathic system, such as tooth wear. However, if it is not clear whether those symptoms are truly caused by sleep bruxism, overtreatment may result. The American Academy of Sleep Medicine has classified the diagnosis by polysomnography as “Definite sleep bruxism”, “Probable sleep bruxism” by clinical signs, and “Possible sleep bruxism” by questionnaire. Clinically, the diagnosis should be made through objective evaluation using a wearable electromyograph or the International Classification of Sleep Disorders third edition criteria for diagnosis based on clinical signs (tooth grinding sounds during sleep and abnormal tooth wear or/and morning jaw symptoms). In addition, the underlying causes of sleep bruxism should be investigated. If it is associated with a background disease, such as secondary sleep bruxism, treatment should proceed in collaboration with medical professionals. If augmenting factors are present, sleep hygiene instructions should be provided. If these treatments are unsuccessful, a well-fitting, properly adjusted occlusal appliance (stabilization-type appliance) may be applied. However, once symptoms have improved, the patient should proceed to discontinue the occlusal appliance.journal articl

    A novel CT‑based radiomics model for predicting response and prognosis of chemoradiotherapy in esophageal squamous cell carcinoma

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    No clinically relevant biomarker has been identified for predicting the response of esophageal squamous cell carcinoma (ESCC) to chemoradiotherapy (CRT). Herein, we established a CT-based radiomics model with artificial intelligence (AI) to predict the response and prognosis of CRT in ESCC. A total of 44 ESCC patients (stage I-IV) were enrolled in this study; training (n = 27) and validation (n = 17) cohorts. First, we extracted a total of 476 radiomics features from three-dimensional CT images of cancer lesions in training cohort, selected 110 features associated with the CRT response by ROC analysis (AUC ≥ 0.7) and identified 12 independent features, excluding correlated features by Pearson’s correlation analysis (r ≥ 0.7). Based on the 12 features, we constructed 5 prediction models of different machine learning algorithms (Random Forest (RF), Ridge Regression, Naive Bayes, Support Vector Machine, and Artificial Neural Network models). Among those, the RF model showed the highest AUC in the training cohort (0.99 [95%CI 0.86–1.00]) as well as in the validation cohort (0.92 [95%CI 0.71–0.99]) to predict the CRT response. Additionally, Kaplan-Meyer analysis of the validation cohort and all the patient data showed significantly longer progression-free and overall survival in the high-prediction score group compared with the low-prediction score group in the RF model. Univariate and multivariate analyses revealed that the radiomics prediction score and lymph node metastasis were independent prognostic biomarkers for CRT of ESCC. In conclusion, we have developed a CT-based radiomics model using AI, which may have the potential to predict the CRT response as well as the prognosis for ESCC patients with non-invasiveness and cost-effectiveness.doctoral thesi

    美馬市郡里地区における「小さな拠点」の設立経緯と現状 : こおざとまちづくり協議会への調査報告

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    Iterative Tomographic Image Reconstruction Algorithm Based on Extended Power Divergence by Dynamic Parameter Tuning

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    Computed tomography (CT) imaging plays a crucial role in various medical applications, but noise in projection data can significantly degrade image quality and hinder diagnosis accuracy. Iterative algorithms for tomographic image reconstruction outperform transform methods, especially in scenarios with severe noise in projections. In this paper, we propose a method to dynamically adjust two parameters included in the iterative rules during the reconstruction process. The algorithm, named the parameter-extended expectation-maximization based on power divergence (PXEM), aims to minimize the weighted extended power divergence between the measured and forward projections at each iteration. Our numerical and physical experiments showed that PXEM surpassed conventional methods such as maximum-likelihood expectation-maximization (MLEM), particularly in noisy scenarios. PXEM combines the noise suppression capabilities of power divergence-based expectation-maximization with static parameters at every iteration and the edge preservation properties of MLEM. The experimental results demonstrated significant improvements in image quality in metrics such as the structural similarity index measure and peak signal-to-noise ratio. PXEM improves CT image reconstruction quality under high noise conditions through enhanced optimization techniques.journal articl

    Symptomatic adverse events of chemotherapy in breast cancer patients : Using CTCAE, PRO-CTCAE, and EORTC QLQ-C30

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    Background : The Common Terminology Criteria for Adverse Events (CTCAE) is used as a tool to evaluate the adverse events (AE) of chemotherapy in cancer patients. Since CTCAE by medical providers underestimates AE more than patient-reported outcomes (PRO), the National Cancer Institute developed PRO-CTCAE. The present study investigated differences between symptoms detected using CTCAE by medical providers and PRO-CTCAE by breast cancer patients. Methods : Patients received chemotherapy comprising epirubicin and cyclophosphamide pre- or postoperatively. AE were evaluated using 4 questionnaires : PRO-CTCAE, CTCAE, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-30), and Hospital Anxiety and Depression Scale (HADS) after 1, 2, and 3 courses of chemotherapy. Results : Forty-two patients were registered. Regarding the recognition of psychological symptoms, such as fatigue, anxiety, and discouragement, and subjective symptoms, including heart palpitations and shortness of breath, PRO using PRO-CTCAE was significantly higher than medical provider-recognized outcomes using CTCAE. Concerning the recognition of regimen-specific symptoms, such as vomiting, nausea, and decreased appetite, medical provider-recognized outcomes were the same or higher than PRO. In QLQ-C30, the physical and role functions, fatigue and dyspnea significantly worsened after 2 and 3 courses of chemotherapy.doctoral thesi

    Synthesis of N-Glyoxylyl Peptides Enabled by a Lossen Rearrangement-Induced Intramolecular Redox Reaction of N-Terminal Glycyl Hydroxamic Acid

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    An oxidant-free approach to the synthesis of N-glyoxylyl peptides has been developed that utilizes the Lossen rearrangement of the N-terminal glycyl hydroxamic acid residue. The synthesis proceeds via an intramolecular redox mech-anism to yield the glyoxylyl peptides, which are then subjected to various peptide cyclization procedures. The reaction scheme is suitable for oxidation-sensitive moieties, including amino acids.journal articl

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