Continuous 5-hydroxymethylfurfural production from monosaccharides in a microreactor

5-Hydroxymethylfurfural (HMF) was effectively produced from monosaccharides in a microreactor. A biphasic reaction system was employed to achieve the immediate extraction of produced HMF and suppress the overreaction. A microreactor was utilized to ensure that the reaction occurred under segmented flow to enhance the extraction efficiency. Through many attempts using phosphate buffer saline (PBS) as the reaction phase and 2-sec-butyl phenol (2BP) as the extraction phase, the favorable conditions were determined. By using PBS with pH of 2.0 and 2BP at a volume ratio of 3 to PBS, 80.9 mol % of fructose and 75.7 mol % of glucose were converted into HMF, respectively, at 180 °C. By comparing the results obtained through monophasic reactions, it was confirmed that the biphasic system successfully suppressed both the overreaction and the byproducts. The system employed only a simple experimental apparatus and the acid solution and organic solvent reagents without any complex expensive catalyst

Understanding the Pathophysiology of Alzheimer's Disease and Mild Cognitive Impairment: A Mini Review on fMRI and ERP Studies

The prevalence of Alzheimer's disease (AD) is predicted to increase rapidly in the coming decade, highlighting the importance of early detection and intervention in patients with AD and mild cognitive impairment (MCI). Recently, remarkable advances have been made in the application of neuroimaging techniques in investigations of AD and MCI. Among the various neuroimaging techniques, functional magnetic resonance imaging (fMRI) has many potential advantages, noninvasively detecting alterations in brain function that may be present very early in the course of AD and MCI. In this paper, we first review task-related and resting-state fMRI studies on AD and MCI. We then present our recent fMRI studies with additional event-related potential (ERP) experiments during a motion perception task in MCI. Our results indicate that fMRI, especially when combined with ERP recording, can be useful for detecting spatiotemporal functional changes in AD and MCI patients

Feasibility of cryopreserved tracheal xenotransplants with the use of short-course immunosuppression

AbstractObjective: We evaluated the feasibility of discordant xenotransplantation of the cryopreserved trachea with intermittent immunosuppression to help solve the shortage of donor tracheas. Methods: Two experiments were performed with heterotopic transplantation models in 14 guinea pigs and 85 rats. So that the minimal dose of FK506 for viable fresh xenografts could be determined, FK506 was given in escalating doses (0, 1.5, 2.5, and 3.5 mg/kg) for recipient animals after xenogeneic transplantation. With the goal of obtaining a long-term survival of the xenografts, the effect of cryopreservation on xenografts was assessed and thereafter different cycles of immunosuppression every third week were evaluated in fresh or cryopreserved xenografts in the second experiment. Results: An FK506 dosage of more than 2.5 mg/kg per day was much more effective than smaller dosages, as demonstrated by morphologic assessment. A higher dosage of FK506 potentially delayed the rejection of xenografts and can thus maintain tracheal xenograft viability for less than 4 weeks in rat recipients. In experiment 2, the cryopreserved xenografts showed less histologic viability than fresh xenografts but greater patency of the lumen. The patency of cryopreserved xenografts was favorably maintained for a longer period than that of fresh xenografts with either the same number or more cycles of immunosuppression. Conclusions: We conclude that the synergistic effect of cryopreservation and adequate intermittent immunosuppression may enable tracheal xenografts to remain viable over longer periods. (J Thorac Cardiovasc Surg 2001;121:241-8

Chronic partial unloading restores β-adrenergic responsiveness and reverses receptor downregulation in failing rat hearts

ObjectivesMechanical unloading with a left ventricular assist device promotes “reverse remodeling,” including restoration of β-adrenergic receptor signaling and function. We compared the effects of partial unloading and complete unloading on β-adrenergic responsiveness and gene expressions in failing rat hearts by use of heterotopic heart–lung or heart transplantation models.MethodsFour weeks after ligation of the left anterior descending artery in Lewis rats, rats with heart failure were divided into 3 groups: infarcted hearts and lungs transplanted into the recipient rats (heart failure–partial unloading, n = 8); infarcted hearts transplanted into the recipient rats (heart failure–complete unloading, n = 7); infarcted (heart failure, n = 8) hearts without transplantation. Normal rats (n = 7) were used as controls. Papillary muscle function and gene expressions were studied at 2 or 4 weeks after transplantation.ResultsIn 2-week models, baseline developed tension of papillary muscles significantly increased in heart failure–partial unloading and heart failure–complete unloading compared with heart failure (0.15 ± 0.07 and 0.12 ± 0.05 g/mm2 vs 0.02 ± 0.01 g/mm2, P < .05). However, in 4-week models, they decreased to 0.11 ± 0.03 and 0.10 ± 0.03 g/mm2. In 4-week but not in 2-week models, the increase from baseline in baseline developed tension produced by β-adrenergic stimulation (isoproterenol, 10−8 and 10−7 mol/L) was significantly increased in heart failure–partial unloading compared with heart failure–complete unloading and heart failure (P < .05). The mRNA expressions of brain natriuretic peptide and β1- and β2-adrenergic receptors were normalized in both 2- and 4-week models of heart failure–partial unloading.ConclusionsChronic partial unloading but not complete unloading improved β-adrenergic responsiveness and normalized brain natriuretic peptide and β1- and β2-adrenergic receptor mRNA expressions in the failing rat hearts

Increased amygdala reactivity following early life stress : a potential resilience enhancer role

Background: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Methods: Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Results: Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Conclusions: Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events

大腸3D-CT検査(CT-colonography)における腸管外病変の検出

大腸疾患患者を対象に大腸3D-CT検査(CT-colonography)を施行し,腸管外病変の検出率,検出された腸管外病変の臨床的重要性の分類および大腸疾患の有無と腸管外病変の関係の3項目について検討した.その結果,対象者112例のうち84.8%の症例に少なくとも1つ以上の腸管外病変を認めた.また,対象例のうち33例(29.5%)にカテゴリーE4(臨床上重要な所見を有する)群に分類される腸管外病変を認めた.そして,カテゴリーE4群のうち大腸内視鏡検査で24例(72.7%)が大腸癌と,4例(12.1%,全例に対する比率:3.6%)が所見なしと診断された.これらのことから,大腸疾患およびその疑いを有する症例にCT-colonographyを施行することは,大腸疾患を有する症例はもとより内視鏡検査で所見なしと診断された症例においても,重大な腸管外病変の早期発見に有用である

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target