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The aim of this cross-sectional survey was to characterize the role of and burden on caregivers of heart failure (HF) patients in Japan, since such data are limited at present. Data from 126 caregivers whose average age was 63.5 years were analyzed. RRx-001 cost Helping to prepare meals/cooking was the most frequently reported activity (47% of caregivers); 24% found this the most burdensome. The most frequently reported physical consequence of caregiving was feeling physically tired (44%); emotionally worrying about the patient (62%) was the most frequent psychological consequence. Approximately half of the caregivers reported that caring for patients impacted their lifestyle. Although 40% of caregivers asked questions to physicians regarding diet or lifestyle modifications, 19% did not ask any. Caregivers play a crucial role in the management of HF patients in Japan but experience physical and emotional burden. Solutions are required to reduce the caregiver burden associated with HF.Mechanisms of the specific systemic response of plant to different adverse factors are poorly understood. We studied the mechanisms acting in wheat (Triticum aestivum L.) under the action of local burn and gradual heating. Both stimuli induce a variation potential (VP) propagation and a biphasic (fast and long-term phases) photosynthetic response in non-stimulated zones of plant with stimulus-specific parameters of the latter the fast phase or long-term phase predominance in responses induced by burn or heating, respectively. The burn-induced VP and photosynthetic response attenuate with distance, while the heating-induced VP and photosynthetic response were of more stable amplitude in distant part of the stimulated plant. VP propagation in both cases induced apoplast alkalization with dynamics well corresponding to such of VP and of the fast phase of photosynthetic response. Gradual heating induced a significant rise in jasmonate production along with a decrease in stomatal conductance with characteristic times well corresponding to the long-term phase of the photosynthetic response. We suppose that the VP-induced pH shift is responsible for in the induction of the fast phase, while jasmonate production for the long-term phase of the photosynthetic response. The revealed differences in the systemic response to stressors studied, apparently, reflect two distinct plant adaptation strategies to fast and slow-growing stimuli. The immediate response in the tissue nearest to the damage zone is the most important under a fast-growing stimulus. The fundamentally different situation is under a slowly-growing stimulus which provokes long-term changes in the plant that ensure the preparation of the whole organism for impending environmental changes.Cycloastragenol [20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane] (CA), the principle sapogenol of many cycloartane-type glycosides found in Astragalus genus, is currently the only natural product in the anti-aging market as telomerase activator. Here, we report biotransformation of 20(27)-octanor-cycloastragenol (1), a thermal degradation product of CA, using Astragalus species originated endophytic fungi, viz. Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae and Camarosporium laburnicola. Fifteen new biotransformation products (2-16) were isolated, and their structures were established by NMR and HRESIMS. Endophytic fungi were found to be capable of performing hydroxylation, oxidation, ring cleavage-methyl migration, dehydrogenation and Baeyer-Villiger type oxidation reactions on the starting compound (1), which would be difficult to achieve by conventional synthetic methods. In addition, the ability of the metabolites to increase telomerase activation in Hekn cells was evaluated, which showed from 1.08 to 12.4-fold activation compared to the control cells treated with DMSO. Among the compounds tested, 10, 11 and 12 were found to be the most potent in terms of telomerase activation with 12.40-, 7.89- and 5.43-fold increase, respectively (at 0.1, 2 and 10 nM concentrations, respectively).Lectins are involved in a wide range of carbohydrate mediated recognition processes. Therefore, the availability of highly performant fluorescent tools tailored for lectin targeting and able to efficiently track events related to such key targets is in high demand. We report here on the synthesis of the glyco-BODIPYs 1 and 2, based on the efficient combination of a Heck-like cross coupling and a Knoevenagel condensation, which revealed efficient in addressing lectins. In particular, glyco-BODIPY 1 has two glycosidase stable C-mannose residues, which act as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) targeting modules. By using live-cell fluorescence microscopy, we proved that BODIPY-mannose 1 was efficiently taken up by immune cells expressing DC-SIGN receptors. Super-resolution stimulated emission depletion (STED) microscopy further revealed that the internalized 1 localized in membranes of endosomes, proving that 1 is a reliable tool also in STED applications. Of note, glyco-BODIPY 1 contains an aryl-azido group, which allows further functionalization of the glycoprobe with bioactive molecules, thus paving the way for the use of 1 for tracking lectin-mediated cell internalization in diverse biological settings.Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes (mbpa, mef2d, u2af2b and matn3b).