Enzymatic treatment, unfermented and fermented fruit-based products: current state of knowledge.

In recent years, food manufacturers are increasingly utilizing enzymes in the production of fruit-based (unfermented and fermented) products to increase yield and maximize product quality in a cost-effective manner. Depending on the fruits and desired product characteristics, different enzymes (e.g. pectinase, cellulase, hemicellulase, amylase, and protease) are used alone or in combinations to achieve optimized processing conditions and improve nutritional and sensorial quality. In this review, the mechanisms of action and sources of different enzymes, as well as their effects on the physicochemical, nutritional, and organoleptic properties of unfermented and fermented fruit-based products are summarized and discussed, respectively. In general, the application of enzymatic hydrolysis treatment (EHT) in unfermented fruit-based product helps to achieve four main purposes: (i) viscosity reduction (easy to filter), (ii) clarification (improved appearance/clarity), (iii) better nutritional quality (increase in polyphenolics) and (iv) enhanced organoleptic characteristic (brighter color and complex aroma profile). In addition, EHT provides numerous other advantages to fermented fruit-based products such as better fermentation efficiency and enrichment in aroma. To meet the demand for new market trends, researchers and manufacturers are increasingly employing non-Saccharomyces yeast (with enzymatic activities) alone or in tandem with Saccharomyces cerevisiae to produce complex flavor profile in fermented fruit-based products. Therefore, this review also evaluates the potential of some non-Saccharomyces yeasts with enzymatic activities and how their utilization helps to tailor wines with unique aroma profile. Lastly, in view of an increase in lactose-intolerant individuals, the potential of fermented probiotic fruit juice as an alternative to dairy-based probiotic products is discussed.

Design, synthesis, and evaluation of azo D-π-A dyes as photothermal agents.

Thirteen readily accessible azo D-π-A dyes, intended for use as photothermal agents, were synthesized using only a few steps. Absorption wavelengths were readily tuned by changing the building blocks, and 6 of these dyes exhibited NIR absorption that would be useful for biomedical applications. Unexpected suppression of an N-C single bond rotation that neighbors the azo bond was observed in the case of 5 dyes. Photothermal conversion efficiency measurements revealed a significant effect of the D moiety in these synthesized azo D-π-A dyes, but neither the π moiety nor the A moiety showed an obvious influence. The obtained results offer valuable information for the design of high-performance azo D-π-A dyes that have utility as photothermal agents.

The design, synthesis, and evaluation of organic dithienopyrrole-based D-π-A dyes for use as sensitizers in photodynamic therapy.

Dithienopyrrole-based organic dyes that combine an electron-donating moiety (D), a π-conjugated bridge moiety (π), and an electron-accepting moiety (A) were designed and synthesized in short steps by previously developed one-pot Suzuki-Miyaura coupling approach. Absorption wavelengths of the dyes were readily tuned by altering the D and A moieties. The use of a strongly electron-withdrawing cyanopyridone acceptor enabled NIR absorption. A synthesized sensitizer, 2j, exerted potent phototoxicity mainly via a Type I mechanism in cells. A nitrogen atom in the dithienopyrrole ring serves as a connecting point for the introduction of functional building blocks that can improve the properties of sensitizers, which makes this D-π-A sensitizer a valuable template for the further development of sensitizers.

Influence of denture surface roughness and host factors on dental calculi formation on dentures: a cross-sectional study.

BACKGROUND: Dental calculi formation on dentures can worsen the oral cavity environment by complicating oral hygiene. However, few studies have investigated the effect of how patients use and manage their dentures, denture surface roughness, and host factors such as oral cavity dryness and saliva properties on denture cleanliness and denture dental calculi formation. Accordingly, we conducted the present survey to evaluate these factors to clarify the strength of the influence of each factor. METHODS: We enrolled 53 patients who had used dentures for at least 3 months and used a dental prosthesis that covered at least the six front teeth including the left and right mandibular canines. After staining the dentures, we divided the participants into a group that was positive for dental calculi (DCP group) and a group that was negative for dental calculi (DCN group). After removing all the stains, we evaluated the surface roughness of the dentures. A questionnaire was used to survey how the participants used and managed their dentures. Oral cavity dryness was evaluated, and resting saliva samples were collected to assess saliva properties. Correlations between the presence or absence of dental calculi and denture use and management were evaluated using a chi-square test. Correlations with denture surface roughness, oral cavity dryness, and saliva properties were evaluated using the Mann-Whitney U test. Correlations between the presence or absence of dental calculi and all factors were analyzed using multivariate analysis (quantification II). RESULTS: Surface roughness was significantly greater in the DCP group (p < 0.01), and the DCP group members wore their dentures during sleep significantly more often and used a denture cleaner when storing their dentures significantly less often (both p < 0.01). No significant differences were observed for oral cavity dryness or saliva properties. The multivariate analysis showed significant correlations of dental calculi formation with denture surface roughness and items related to denture use and management, but not for oral cavity dryness or saliva properties. CONCLUSIONS: Our findings indicate that dental calculi formation is influenced by how dentures are used and managed and by denture surface roughness, but not by oral cavity dryness and saliva properties.

The Design, Synthesis, and Evaluation of 1,5,7-Trisubstituted-3-Pyridyl-Xanthones for Use as Insecticides Starting from Pyripyropene†A.

A readily accessible template of 1,5,7-trisubstituted-3-pyridyl-xanthones was designed starting from naturally occurring pyripyropene A for agrichemical development. Our originally developed Ag2 CO3 -mediated oxidative cyclization enabled ready access to the key scaffold, 1,5,7-trihydroxy-3-chloro-xanthone. The chemo- and regioselective sequential introduction of four substituents to the scaffold rapidly afforded the desired, structurally diverse 1,5,7-trisubstituted-3-pyridyl-xanthones. An evaluation of insecticidal activity revealed that one of the synthesized compounds retained insecticidal activity against vetch aphid and green peach aphid. The observed insecticidal spectrum was similar to that of pyripyropene A. The developed template could be a valuable aid for future agrichemical development.

Asymmetric Total Synthesis of ent-Pyripyropene†A.

An asymmetric total synthesis of ent-pyripyropene A was achieved by a convergent synthetic route. We used our originally developed Ti(III) -catalyzed radical cyclization to construct an AB-ring portion that consisted of a trans-decalin skeleton with five contiguous stereogenic centers. The coupling between the AB-ring and the DE-ring portions, and a subsequent C-ring cyclization, led to the total synthesis of ent-pyripyropene A. An evaluation of the insecticidal activity of ent-pyripyropene A against two aphid species revealed that ent-pyripyropene A was 35-175 times less active than naturally occurring pyripyropene A. This result indicated that the biological target of pyripyropene A recognizes the absolute configuration of pyripyropene A.

Rapid Synthesis of Thiophene-Based, Organic Dyes for Dye-Sensitized Solar Cells (DSSCs) by a One-Pot, Four-Component Coupling Approach.

This one-pot, four-component coupling approach (Suzuki-Miyaura coupling/C-H direct arylation/Knoevenagel condensation) was developed for the rapid synthesis of thiophene-based organic dyes for dye-sensitized solar cells (DSSCs). Seven thiophene-based, organic dyes of various donor structures with/without the use of a 3,4-ethylenedioxythiophene (EDOT) moiety were successfully synthesized in good yields based on a readily available thiophene boronic acid pinacol ester scaffold (one-pot, 3-step, 35-61%). Evaluation of the photovoltaic properties of the solar cells that were prepared using the synthesized dyes revealed that the introduction of an EDOT structure beside a cyanoacrylic acid moiety improved the short-circuit current (Jsc) while decreasing the fill factor (FF). The donor structure significantly influenced the open-circuit voltage (Voc), the FF, and the power conversion efficiency (PCE). The use of a n-hexyloxyphenyl amine donor, and our originally developed, rigid, and nonplanar donor, both promoted good cell performance (η=5.2-5.6%).

Sema3a maintains normal heart rhythm through sympathetic innervation patterning.

Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a, establishes cardiac sympathetic innervation patterning. Sema3a is abundantly expressed in the trabecular layer in early-stage embryos but is restricted to Purkinje fibers after birth, forming an epicardial-to-endocardial transmural sympathetic innervation patterning. Sema3a(-/-) mice lacked a cardiac sympathetic innervation gradient and exhibited stellate ganglia malformation, which led to marked sinus bradycardia due to sympathetic dysfunction. Cardiac-specific overexpression of Sema3a in transgenic mice (SemaTG) was associated with reduced sympathetic innervation and attenuation of the epicardial-to-endocardial innervation gradient. SemaTG mice demonstrated sudden death and susceptibility to ventricular tachycardia, due to catecholamine supersensitivity and prolongation of the action potential duration. We conclude that appropriate cardiac Sema3a expression is needed for sympathetic innervation patterning and is critical for heart rate control.

Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.

The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.

Left circumflex coronary artery is protected against no-reflow phenomenon following percutaneous coronary intervention for coronary artery disease.

Despite the positive impact of percutaneous coronary intervention (PCI) on reducing mortality, a small percentage of patients experience poor myocardial reperfusion following PCI. However, factors associated with no-reflow remain unclear. We investigated clinical factors associated with no-reflow following PCI for coronary artery disease (CAD). We retrospectively analyzed 1622 consecutive CAD patients who underwent PCI over a 5-year period at our institution. Patients were divided into two groups according to the presence (n = 31) or absence (n = 1591) of no-reflow, defined as Thrombolysis in Myocardial Infarction flow grade <3 after PCI. No significant differences in patient characteristics or PCI strategy were seen between the no-reflow and normal flow groups. The incidence of no-reflow was significantly lower in the left circumflex artery (LCx) than in the left anterior descending artery (LAD) (P = 0.0015), with no differences in characteristics or PCI strategy between these two target vessels. Multivariate analysis revealed that involvement of the LCx was an independent protective factor against no-reflow (odds ratio 0.14, 95 % confidence interval 0.02-0.98, P = 0.044). In conclusion, LCx as the target vessel was protective against no-reflow compared with LAD following PCI for CAD. Our results suggest that embolic protection devices may be unnecessary in CAD patients with involvement of LCx.

Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction.

OBJECTIVE: We recently demonstrated that primitive neural crest-derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI). METHODS AND RESULTS: We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed-enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter. CONCLUSIONS: These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.

Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart.

Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell-, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0-Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells-and under the right conditions-differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.

Observation of sublimation of ice using terahertz spectroscopy.

Although many studies have investigated the phase change of water, few have focused on the sublimation of ice. This study revealed that ice sublimation can be observed using terahertz (THz) spectroscopy. From measurements in the range of 210-270 K, the sublimation was observed over the entire temperature range and the rate of sublimation was increased proportionally with temperature. Particularly on a time scale of a few hundred minutes, the sublimation progresses visibly above 250 K. Above a certain temperature, the absorption coefficient increased during sublimation. These findings suggest that an interesting phenomenon may occur in the phase change of water at sub-zero temperatures, indicating that THz spectroscopy would be useful for measuring water and ice.

Effectiveness of a clinical pathway for complete denture adjustment.

This study was performed to evaluate the usefulness of a developed clinical pathway (CP) to determine the sequence of dental treatment in patients who are edentulous and use maxillary and mandibular complete dentures. Sixty-two edentulous patients with maxillary and mandibular complete dentures were randomly allocated either to with (31 subjects) or without (31 subjects) a CP. The main categories of the CP were the examination, instructions, practice, idle time, evaluation sheet, preparation, and other steps. The subcategories were made with respect to the main categories. The participants were categorized as dentists, assistants, or patients. There was no significant difference in mean chair time between with a CP (27.5 min) and without a CP (28.0 min). The CP led to a significant reduction in idle time (waiting in the chair or no treatment) of dentists, assistants, and patients. In contrast, the instances of medical examination, patients' instructions, and the number of patients reporting improvement of symptoms significantly increased. These results indicated that there is an opportunity to improve the complete denture treatment with a CP.

Contemporary trend of reduced-dose non-vitamin K anticoagulants in Japanese patients with atrial fibrillation: A cross-sectional analysis of a multicenter outpatient registry.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used to prevent stroke in non-valvular atrial fibrillation (NVAF) patients. Stringent monitoring is not required for NOACs, albeit dose adjustments are needed based on specific patient factors, such as renal function, body weight and age, or concomitant medications. We investigated the NOAC dosing patterns and evaluated the predictors of the non-standardized dose reduction (NSDR). METHODS: A total of 2452 newly diagnosed NVAF patients were consecutively recruited from secondary- and tertiary-care hospitals between 2012 and 2017. The NOAC doses were classified as one of three: (1) full dose; (2) standardized dose reduction (SDR); or (3) NSDR, consistent with Japanese package inserts. RESULTS: Overall, 66.8% (N=1637) of the NVAF patients (median age: 69 years, interquartile range [IQR]: 60-76; 70% male; median CHA2DS2-VASc score of 2, IQR: 1-3) received NOACs. NOAC use dramatically increased during the study period (51.2% in 2012-13 to 74.4% in 2016-17). The percentages of SDR and NSDR were 19.6% and 14.4%, respectively; a proportion of SDR and NSDR did not alter drastically. Older age, concomitant antiplatelet therapy, impaired renal function, and prior heart failure or left ventricular dysfunction were independently associated with NSDR. Of note, patients with a high risk (CHA2DS2-VASc score ≥2) had the highest proportion of NSDRs. CONCLUSIONS: Nearly half of the NOAC dose reductions in our registry were deemed "non-standardized," which were seen mostly in patients at significant risk for ischemic stroke. The physician's apprehension regarding excessive bleeding under NOAC use should be appropriately balanced with concern for an increased risk of embolic events.

Nerve growth factor is critical for cardiac sensory innervation and rescues neuropathy in diabetic hearts.

BACKGROUND: Molecular mechanisms regulating the cardiac sensory nervous system remain poorly understood. Cardiac sensory nerve impairment causes silent myocardial ischemia, a main cause of sudden death in diabetes mellitus (DM). The present study focused on the roles of nerve growth factor (NGF) in the regulation of the cardiac sensory nervous system and analyzed the mechanism of silent myocardial ischemia in DM. METHODS AND RESULTS: We screened neurotrophic factors and found that cardiac sensory nerves developed in parallel with NGF synthesized in the heart. Cardiac nociceptive sensory nerves that were immunopositive for calcitonin gene-related peptide, dorsal root ganglia (DRG), and the dorsal horn were markedly retarded in NGF-deficient mice, whereas cardiac-specific overexpression of NGF rescued these deficits. DM was induced with streptozotocin in wild-type and transgenic mice overexpressing NGF in the heart. Downregulation of NGF, calcitonin gene-related peptide-immunopositive cardiac sensory denervation, and atrophic changes in DRG were observed in DM-induced wild-type mice, whereas these deteriorations were reversed in DM-induced NGF transgenic mice. Cardiac sensory function, measured by myocardial ischemia-induced c-Fos expression in DRG, was also downregulated by DM in the wild-type mice but not in NGF transgenic mice. Direct gene transfer of NGF in the diabetic rat hearts improved impaired cardiac sensory innervation and function, determined by electrophysiological activity of cardiac afferent nerves during myocardial ischemia. CONCLUSIONS: These findings demonstrate that the development and regulation of the cardiac sensory nervous system are dependent on NGF synthesized in the heart and that DM-induced NGF reduction causes cardiac sensory neuropathy.

Sequential S(N)Ar Reaction/Suzuki-Miyaura Coupling/C-H Direct Arylations Approach for the Rapid Synthesis of Tetraaryl-Substituted Pyrazoles.

A rapid synthesis of 1,3,4,5-tetraaryl-substituted pyrazoles has been achieved through a sequence of SN Ar reaction/Suzuki-Miyaura coupling/Pd-catalyzed direct arylations that used 3-iodo-1H-pyrazole as a scaffold. Pyrazoles with four different aryl groups were synthesized in a straightforward manner with no extra synthetic steps, such as protection/deprotection or the introduction of activating/directing groups, using readily available substrates and reagents. The developed synthetic approach enabled the structurally diverse synthesis of multiaryl-substituted pyrazoles without using a glovebox technique.

Development of dual targeting inhibitors against aggregations of amyloid-ß and tau protein.

Aggregations of both amyloid-ß (Aß) and hyper-phosphorylated tau proteins are recognized as key pathological manifestations of Alzheimer's disease (AD). Agents that inhibit both those forms of aggregation show promise as drug candidates. Seventeen oligo heteroaromatic compounds were rapidly synthesized via a one-pot, 3- or 4-component coupling procedure. Evaluations showed that compounds E16 and E18 were the most potent inhibitors of Aß and tau aggregations (E16: IC50s = 0.38, 0.29 µM against Aß, tau, respectively, E18: IC50s = 0.55, 0.30 µM against Aß, tau, respectively).

Elucidation of the structure-property relationship of p-type organic semiconductors through rapid library construction via a one-pot, Suzuki-Miyaura coupling reaction.

The elucidation of the structure-property relationship is an important issue in the development of organic electronics. Combinatorial synthesis and the evaluation of systematically modified compounds is a powerful tool in the work of elucidating structure-property relationships. In this manuscript, D-π-A structure, 32 p-type organic semiconductors were rapidly synthesized via a one-pot, Suzuki-Miyaura coupling with subsequent Knoevenagel condensation. Evaluation of the solubility and photovoltaic properties of the prepared compounds revealed that the measured solubility was strongly correlated with the solubility parameter (SP), as reported by Fedors. In addition, the SPs were correlated with the Jsc of thin-film organic solar cells prepared using synthesized compounds. Among the evaluated photovoltaic properties of the solar cells, Jsc and Voc had strong correlations with the photoconversion efficiency (PCE).