Bioelectronic implantable systems (BIS) targeting biomedical and clinical research should combine long‐term performance and biointegration in vivo. Here, recent advances in novel encapsulations to ...protect flexible versions of such systems from the surrounding biological environment are reviewed, focusing on material strategies and synthesis techniques. Considerable effort is put on thin‐film encapsulation (TFE), and specifically organic–inorganic multilayer architectures as a flexible and conformal alternative to conventional rigid cans. TFE is in direct contact with the biological medium and thus must exhibit not only biocompatibility, inertness, and hermeticity but also mechanical robustness, conformability, and compatibility with the manufacturing of microfabricated devices. Quantitative characterization methods of the barrier and mechanical performance of the TFE are reviewed with a particular emphasis on water‐vapor transmission rate through electrical, optical, or electrochemical principles. The integrability and functionalization of TFE into functional bioelectronic interfaces are also discussed. TFE represents a must‐have component for the next‐generation bioelectronic implants with diagnostic or therapeutic functions in human healthcare and precision medicine.
The state of the art and recent advances in encapsulations of flexible bioelectronic chronic implants are reviewed. The materials, deposition and application technologies, and cutting‐edge characterization methods are described in detail. Smart encapsulations integrated into microfabrication, patterned, and actively interacting with the surrounding tissues are also highlighted.
Glucocorticoid (GC) is an adrenal steroid hormone that controls a variety of physiological processes such as metabolism, immune response, cardiovascular activity, and brain function. In addition to ...GC induction in response to stress, even in relatively undisturbed states its circulating level is subjected to a robust daily variation with a peak around the onset of the active period of the day. It has long been believed that the synthesis and secretion of GC are primarily regulated by the hypothalamus–pituitary–adrenal (HPA) neuroendocrine axis. However, recent chronobiological research strongly supports the idea that multiple regulatory mechanisms along with the classical HPA neuroendocrine axis underlie the diurnal rhythm of circulating GC. Most notably, recent studies demonstrate that the molecular circadian clockwork is heavily involved in the daily GC rhythm at multiple levels. The daily GC rhythm is implicated in various human diseases accompanied by abnormal GC levels. Patients with such diseases frequently show a blunted GC rhythmicity and, more importantly, circadian rhythm-related symptoms. In this review, we focus on recent advances in the understanding of the circadian regulation of adrenal GC and its implications in human health and disease.
► Current understanding of circadian control of the adrenal gland. ► Multiple regulatory mechanisms underlying the daily rhythm of glucocorticoid (GC). ► Role of the adrenal local clockwork in circadian GC production. ► Importance of GC rhythm in human health and diseases.
Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no ...GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing. We found that GC prominently induced Per2 expression and delayed the circadian phase. The overlapping GRE and E-box (GE2) region in the proximal Per2 promoter was responsible for GC-mediated Per2 induction. The GRE in the Per2 promoter was unique in that brain and muscle ARNT-like protein-1 (BMAL1) was essential for GC-induced Per2 expression, whereas other GRE-containing promoters, such as Per1 and mouse mammary tumor virus, responded to dexamethasone in the absence of BMAL1. This specialized regulatory mechanism was mediated by BMAL1-dependent binding of the GC receptor to GRE in Per2 promoter. When Per2 induction was abrogated by the mutation of the GRE or E-box, the circadian oscillation phase failed to be delayed compared with that of the wild-type. Therefore, the current study demonstrates that the rapid Per2 induction mediated by GC is crucial for delaying the circadian rhythm.
Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery ...and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons. Although CoMIC is potentiated by inhibition of Drp1 and occurs at the potential division spots contacting the endoplasmic reticulum, it appears on IMM independently of OMM. Intra-mitochondrial influx of Ca
induces and potentiates CoMIC, and leads to K
-mediated mitochondrial bulging and depolarization. Synergistically, optic atrophy 1 (Opa1) also regulates CoMIC via controlling Mic60-mediated OMM-IMM tethering. Therefore, we propose that CoMIC is a priming event for efficient mitochondrial division.
The novel neuropeptide spexin (SPX) was discovered using bioinformatics. The function of this peptide is currently under investigation. Here, we identified SPX along with a second SPX gene (SPX2) in ...vertebrate genomes. Syntenic analysis and relocating SPXs and their neighbor genes on reconstructed vertebrate ancestral chromosomes revealed that SPXs reside in the near vicinity of the kisspeptin (KISS) and galanin (GAL) family genes on the chromosomes. Alignment of mature peptide sequences showed some extent of sequence similarity among the 3 peptide groups. Gene structure analysis indicated that SPX is more closely related to GAL than KISS. These results suggest that the SPX, GAL, and KISS genes arose through local duplications before 2 rounds (2R) of whole-genome duplication. Receptors of KISS and GAL (GAL receptor GALR) are phylogenetically closest among rhodopsin-like G protein-coupled receptors, and synteny revealed the presence of 3 distinct receptor families KISS receptor, GALR1, and GALR2/3 before 2R. A ligand-receptor interaction study showed that SPXs activate human, Xenopus, and zebrafish GALR2/3 family receptors but not GALR1, suggesting that SPXs are natural ligands for GALR2/3. Particularly, SPXs exhibited much higher potency toward GALR3 than GAL. Together, these results identify the coevolution of SPX/GAL/KISS ligand genes with their receptor genes. This study demonstrates the advantage of evolutionary genomics to explore the evolutionary relationship of a peptide gene family that arose before 2R by local duplications.
Highlights ► Circadian rhythm of glucocorticoid (GC) is tightly regulated by coincident multiple mechanisms. ► Adrenal local clock regulates periodic steroidogenesis and responsiveness of adrenal GC ...to ACTH. ► Adrenal clock links the central clock and peripheral clocks in the organization of the clock system. ► Adrenal rhythm have an important role in harmonizing circadian physiology and behavior.
The association between metabolic syndrome and eating patterns remains unclear. We hypothesized that Korean Healthy Eating Index (KHEI) scores were related to metabolic syndrome (MetS) risk in adults ...in a gender-dependent manner. We aimed to examine the hypothesis using the Korea National Health and Nutrition Examination Survey-VI (2013-2017) data with a complex sample survey design. Adjusted means and 95% confidence intervals of KHEI scores and nutrient intake estimated by the 24-h recall were calculated according to MetS status after adjusting for age, residence area, region, education, obesity, income, drinking status, smoking status, marriage, and exercise. Adjusted odds ratios for MetS were measured according to KHEI quartiles using logistic regression analysis while controlling for covariates. MetS incidence was significantly higher in females than in males. Those who were older, less educated, earning less income, more obese, living in rural areas, drinking severely, non-exercising, and married had higher MetS incidence than those with the opposite state. Total KHEI scores of all components KHEI scores were lower for those with MetS (MetS group) than those without MetS (Non-MetS group) in both genders. For KHEI components, having breakfast and milk and fat intake had lower scores for the MetS group than for the Non-MetS group in women, whereas fruits and milk and milk product intake had lower scores for the MetS group in men. Nutrient intake influenced the MetS risk in females more than in males. Fat, calcium, and vitamin C intakes from 24-h recall were lower in the MetS group than in the Non-MetS group in women. KHEI scores had an inverse association with MetS risk by 0.98-fold in both genders after adjusting for covariates. In conclusion, a healthy diet that includes adequate calcium and vitamin C is associated with a lower the risk of MetS in both men and women.
The purpose of this study was to develop and validate a scale for predicting the intention of pre-service physical activity instructors for persons with disabilities to participate in pro bono work, ...based on the Theory of Planned Behavior. This study analyzed 322 university students majoring in adapted physical activity in South Korea. To determine the purpose of the study, the EFA using SPSS 21.0 and CFA using AMOS 21.0 were used to confirm the validity of the measurement tool and the relationship between latent and observed variables. Further, the Cronbach’s alpha was used to identify the internal reliability. As a result, first, the questionnaire used in this study was validated based on the theory. Second, the behavioral belief was influenced by teaching experience about physical activity for the disabled and knowledge about physical activity for the disabled. Third, the normative belief was influenced by the parents of people with disabilities, people with disabilities, family members, friends, and students in my department. Fourth, the control belief was influenced by the state of mind of physical activity instructors for people with disabilities, the ability to create an IEP, and the ability to do physical activity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human ...transmission. Nevertheless, there are no specific treatments clinically approved. This study aimed to compare antiviral activity of gemcitabine and its analogue 2'-fluoro-2'-deoxycytidine (2FdC) against SARS-CoV-2 as well as cytotoxicity in vitro. Fluorescent image-based antiviral assays revealed that gemcitabine was highly potent, with a 50% effective concentration (EC
) of 1.2 μM, more active than the well-known nucleoside monophosphate remdesivir (EC
= 35.4 μM). In contrast, 2FdC was marginally active (EC
= 175.2 μM). For all three compounds, the 50% cytotoxic concentration (CC
) values were over 300 μM toward Vero CCL-81 cells. Western blot and quantitative reverse-transcription polymerase chain reaction analyses verified that gemcitabine blocked viral protein expression in virus-infected cells, not only Vero CCL-81 cells but also Calu-3 human lung epithelial cells in a dose-dependent manner. It was found that gemcitabine has a synergistic effect when combined with remdesivir. This report suggests that the difluoro group of gemcitabine is critical for the antiviral activity and that its combination with other evaluated antiviral drugs, such as remdesivir, could be a desirable option to treat SARS-CoV-2 infection.
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