The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.

Formation of transport vesicles requires the coordinate activity of the coating machinery that selects cargo into the nascent vesicle and the membrane bending machinery that imparts curvature to the forming bud. Vesicle coating at the trans-Golgi Network (TGN) involves AP1, GGA2 and clathrin, which are recruited to membranes by activated ARF GTPases. The ARF activation at the TGN is mediated by the BIG1 and BIG2 guanine nucleotide exchange factors (GEFs). Membrane deformation at the TGN has been shown to be mediated by lipid flippases, including ATP8A1, that moves phospholipids from the inner to the outer leaflet of the TGN membrane. We probed a possible coupling between the coating and deformation machineries by testing for an interaction between BIG1, BIG2 and ATP8A1, and by assessing whether such an interaction may influence coating efficiency. Herein, we document that BIG1 and BIG2 co-localize with ATP8A1 in both, static and highly mobile TGN elements, and that BIG1 and BIG2 bind ATP8A1. We show that the interaction involves the catalytic Sec7 domain of the GEFs and the cytosolic C-terminal tail of ATP8A1. Moreover, we report that the expression of ATP8A1, but not ATP8A1 lacking the GEF-binding cytosolic tail, increases the generation of activated ARFs at the TGN and increases the selective recruitment of AP1, GGA2 and clathrin to TGN membranes. This occurs without increasing BIG1 or BIG2 levels at the TGN, suggesting that the binding of the ATP8A1 flippase tail to the Sec7 domain of BIG1/BIG2 increases their catalytic activity. Our results support a model in which a flippase component of the deformation machinery impacts the activity of the GEF component of the coating machinery.

Lack of nuclear localization of the Creb3l1 transcription factor causes defects in caudal fin bifurcation in zebrafish Danio rerio.

The formation of normal bone and bone healing require the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after fracture. Creb3l1 undergoes regulated intra-membrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. To expand our understanding of Creb3l1 role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish D. rerio caused a frame-shift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ doesn't regulate transcription, and the creb3l1TA+/TA+ fish animals are creb3l1 transcriptional nulls. We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased capacity for regeneration, and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway, and document a novel role of Creb3l1 in tissue patterning.

Identifying facilitators of and barriers to the adoption of dynamic consent in digital health ecosystems: a scoping review.

BACKGROUND: Conventional consent practices face ethical challenges in continuously evolving digital health environments due to their static, one-time nature. Dynamic consent offers a promising solution, providing adaptability and flexibility to address these ethical concerns. However, due to the immaturity of the concept and accompanying technology, dynamic consent has not yet been widely used in practice. This study aims to identify the facilitators of and barriers to adopting dynamic consent in real-world scenarios. METHODS: This scoping review, conducted in December 2022, adhered to the PRISMA Extension for Scoping Reviews guidelines, focusing on dynamic consent within the health domain. A comprehensive search across Web of Science, PubMed, and Scopus yielded 22 selected articles based on predefined inclusion and exclusion criteria. RESULTS: The facilitators for the adoption of dynamic consent in digital health ecosystems were the provision of multiple consent modalities, personalized alternatives, continuous communication, and the dissemination of up-to-date information. Nevertheless, several barriers, such as consent fatigue, the digital divide, complexities in system implementation, and privacy and security concerns, needed to be addressed. This study also investigated current technological advancements and suggested considerations for further research aimed at resolving the remaining challenges surrounding dynamic consent. CONCLUSIONS: Dynamic consent emerges as an ethically advantageous method for digital health ecosystems, driven by its adaptability and support for continuous, two-way communication between data subjects and consumers. Ethical implementation in real-world settings requires the development of a robust technical framework capable of accommodating the diverse needs of stakeholders, thereby ensuring ethical integrity and data privacy in the evolving digital health landscape.

Full-Color Solar-Heat-Resistant Films Based on Nanometer Optical Coatings.

Nanometer optical coatings with absorbing materials allow the tuning of structured absorption spectra, thus developing ultrathin color devices. However, these coatings are limited by the narrow bandwidth and tunability of wavelength that restrict the chroma and hue characteristics of colors, respectively, apart from imposing adverse thermal problems under sunlight exposure. Here, we demonstrate that inversely designed TiN/ZnS/Ag coatings attain a wide color gamut in the trilayer configuration and efficiently dissipate heat through thermal radiation when transfer-printed on high-emissivity polymers. Daytime experiments reveal that fabricated optical films yield an almost color-independent heat dissipation rate against solar heating. Moreover, they outperform commercial paints of the same color when applied to three-dimensional miniature houses. All magenta, green, cyan, and yellow optical films lower the roof temperature by 10, 6, 8, and 2 °C below one sun irradiance, respectively, compared to their paint counterparts; the temperature gradient increases directly with the level of sunlight.

Synthesis of 1,4-Dialkoxynaphthalene-Based Imidazolium Salts and Their Cytotoxicity in Cancer Cell Lines.

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.

Sirt2 positively regulates muscle regeneration after Notexin-induced muscle injury.

Sirt2 regulates various biological processes by deacetylating target genes. Despite roles in regulating proliferation, cell cycle, and glucose metabolism, which are closely associated with skeletal muscle physiology, Sirt2 functions in this tissue remain unclear. In this study, genetic deletion of Sirt2 delayed muscle regeneration after Notexin-induced muscle injury. Gene expressions of myogenic regulatory factors, including Myf5, MyoD, and Myogenin, and cell cycle regulators, such as cyclin D1 and CDK2, were repressed in Sirt2 knockout mice after injury. Also, Sirt2 knockout mice presented muscle atrophy after muscle injury which is associated with the down-regulation of anabolic signaling and the up-regulation of catabolic signaling, in particular, increased atrogin1 transcriptional expression. Thus, Sirt2 positively regulated skeletal muscle regeneration after muscle injury by regulating transcriptional expression involved in myogenesis, cell cycle, and anabolic and catabolic signaling. Based on the in vivo analyses, Sirt2 could function as an interventional therapeutic for chronic myopathy, which is characterized by impaired muscle regeneration and muscle atrophy.

Aqueous extracts of Corni Fructus protect C2C12 myoblasts from DNA damage and apoptosis caused by oxidative stress.

BACKGROUND: Although the various pharmacological effects of Corni Fructus are highly correlated with its antioxidant activity, the blocking effect against oxidative stress in muscle cells is not clear. The purpose of this study was to investigate the effect of aqueous extracts of Corni Fructus (CFE) against oxidative stress caused by hydrogen peroxide (H2O2) in murine skeletal C2C12 myoblasts. METHODS AND RESULTS: MTT assay for cell viability, DCF-DA staining for reactive oxygen species (ROS) production, Comet assay for DNA damage, annexin V-FITC and PI double staining for apoptosis, JC-1 staining and caspase assay for monitor mitochondrial integrity, and western blotting for related protein levels were conducted in H2O2 oxidative stressed C2C12 cells. Our results showed that CFE pretreatment significantly ameliorated the loss of cell viability and inhibited apoptosis in H2O2-treated C2C12 cells in a concentration-dependent manner. DNA damage induced by H2O2 was also markedly attenuated in the presence of CFE, which was associated with suppression of ROS generation. In addition, H2O2 reduced mitochondrial membrane potential and caused downregulation of Bcl-2 and upregulation of Bax expression, although these were abrogated by CFE pretreatment. Moreover, CFE blocked H2O2-induced cytosolic release of cytochrome c, activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase. CONCLUSION: Taken together, the present results demonstrate that CFE could protect C2C12 cells from H2O2-induced damage by eliminating ROS generation, thereby blocking mitochondria-mediated apoptosis pathway. These results indicate that CFE has therapeutic potential for the prevention and treatment of oxidative stress-mediated myoblast injury.

Catatonia in pediatric obsessive-compulsive disorder: report of two cases.

Catatonia is a psychomotor syndrome which may occur in a wide variety of medical, neurological, and psychiatric conditions. In pediatrics, this condition is rare and is associated with high morbidity and mortality if not correctly diagnosed and treated. Catatonia in obsessive-compulsive disorder is an infrequent association that has been understudied and underdiagnosed. To add to the knowledge on this unusual clinical presentation, two pediatric patients are reported and discussed together with the other two cases described in the literature. These four cases in total of catatonia associated with OCD confirm that it is a relationship that is infrequently reported, possibly because of lack of awareness in clinicians that catatonia can also be caused by OCD, and because the similarity between some catatonic signs and some compulsive phenomena may compound the identification of the former. Most cases of catatonia in this small series seemed to have responded to the optimization of the treatment for OCD. This highlights the clinical importance of an accurate diagnosis of catatonia when associated with OCD.

Decrease in hospital admissions for respiratory diseases during the COVID-19 pandemic: a nationwide claims study.

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively.

Nanometer-optical-coating-based visibly tinted films with 24-hour sub-atmospheric passive cooling.

Colored films absorb solar radiation at specific visible wavelengths, and they consequently heat up above atmospheric temperatures when exposed to sunlight. In this Letter, we report nanometer-thick TiN-based multilayers of light cyan, magenta, and yellow colors that can provide 24 h sub-atmospheric cooling when covered with high-emissivity polymers. Outdoor experiments have demonstrated that these visibly tinted films retain sub-atmospheric temperatures during daytime and nighttime. All fabricated films generated almost color-independent cooling powers and even surpassed commercial white paint at TiN thicknesses <5nm. Our work thus highlights the potential of multispectral selective absorbers as esthetic passive coolers.

Identification and comparison of missed nursing care in the United States of America and South Korea.

AIMS AND OBJECTIVES: This study aimed to identify and compare missed nursing care types and reasons between South Korea and the United States of America. BACKGROUND: Patient safety has become a significant task of the healthcare delivery systems worldwide. The omission of nursing care constitutes a growing concern because it threatens both patient safety and nursing care quality. DESIGN: This study used a cross-sectional, descriptive and comparative design. METHODS: Data were collected from registered nurses working in two university-affiliated tertiary hospitals and a general hospital in Korea and a Midwest United States tertiary hospital. In addition, the STROBE checklist was used in this study. RESULTS: While substantial, the level of missed nursing care reported by Korean nurses was lower than that of United States nurses. Only three nursing care activities, setting up meals, patient assessment and skin/wound care, did not significantly differed between two countries. More basic nursing care types such as ambulation, feeding and mouth care were missed more than others in both countries. The reasons for missed care differed between two countries. However, both Korean and US nurses reported labour resource problems as reasons for missed care. CONCLUSIONS: Although the types of missed nursing care differed significantly between countries, both Korean and US nurses reported labour resource problems for the top reasons for missed care. Thus, comparing missed nursing care could assist nursing administrators in developing strategies to improve care quality and patient safety. RELEVANCE TO CLINICAL PRACTICE: The level and reasons for missed nursing care are very influential factors for patient outcomes and patient safety. Appropriate skill mix and staffing are needed to decrease extent of missed care, so that enhancing patient safety and quality of nursing care.

The ARF guanine nucleotide exchange factor GBF1 is targeted to Golgi membranes through a PIP-binding domain.

ADP-ribosylation factors (ARF) GTPases are activated by guanine nucleotide exchange factors (GEFs) to support cellular homeostasis. Key to understanding spatio-temporal regulation of ARF signaling is the mechanism of GEF recruitment to membranes. Small GEFs are recruited through phosphoinositide (PIP) binding by a pleckstrin homology (PH) domain downstream from the catalytic Sec7 domain (Sec7d). The large GEFs lack PH domains, and their recruitment mechanisms are poorly understood. We probed Golgi recruitment of GBF1, a GEF catalyzing ARF activation required for Golgi homeostasis. We show that the homology downstream of Sec7d-1 (HDS1) regulates Golgi recruitment of GBF1. We document that GBF1 binds phosphoinositides, preferentially PI3P, PI4P and PI(4,5)P2, and that lipid binding requires the HDS1 domain. Mutations within HDS1 that reduce GBF1 binding to specific PIPs in vitro inhibit GBF1 targeting to Golgi membranes in cells. Our data imply that HDS1 and PH domains are functionally analogous in that each uses lipid-based membrane information to regulate GEF recruitment. Lipid-based recruitment of GBF1 extends the paradigm of lipid regulation to small and large GEFs and suggests that lipid-based mechanisms evolved early during GEF diversification. This article has an associated First Person interview with the first author of the paper.

A Redundant Mechanism of Recruitment Underlies the Remarkable Plasticity of the Requirement of Poliovirus Replication for the Cellular ArfGEF GBF1.

The replication of many positive-strand RNA viruses [(+)RNA viruses] depends on the cellular protein GBF1, but its role in the replication process is not clear. In uninfected cells, GBF1 activates small GTPases of the Arf family and coordinates multiple steps of membrane metabolism, including functioning of the cellular secretory pathway. The nonstructural protein 3A of poliovirus and related viruses has been shown to directly interact with GBF1, likely mediating its recruitment to the replication complexes. Surprisingly, viral mutants with a severely reduced level of 3A-GBF1 interaction demonstrate minimal replication defects in cell culture. Here, we systematically investigated the conserved elements of GBF1 to understand which determinants are important to support poliovirus replication. We demonstrate that multiple GBF1 mutants inactive in cellular metabolism could still be fully functional in the replication complexes. Our results show that the Arf-activating property, but not the primary structure of the Sec7 domain, is indispensable for viral replication. They also suggest a redundant mechanism of recruitment of GBF1 to the replication sites, which is dependent not only on direct interaction of the protein with the viral protein 3A but also on determinants located in the noncatalytic C-terminal domains of GBF1. Such a double-targeting mechanism explains the previous observations of the remarkable tolerance of different levels of GBF1-3A interaction by the virus and likely constitutes an important element of the resilience of viral replication.IMPORTANCE Enteroviruses are a vast group of viruses associated with diverse human diseases, but only two of them could be controlled with vaccines, and effective antiviral therapeutics are lacking. Here, we investigated in detail the contribution of a cellular protein, GBF1, in the replication of poliovirus, a representative enterovirus. GBF1 supports the functioning of cellular membrane metabolism and is recruited to viral replication complexes upon infection. Our results demonstrate that the virus requires a limited subset of the normal GBF1 functions and reveal the elements of GBF1 essential to support viral replication under different conditions. Since diverse viruses often rely on the same cellular proteins for replication, understanding the mechanisms by which these proteins support infection is essential for the development of broad-spectrum antiviral therapeutics.

The Guanine Nucleotide Exchange Factor GBF1 Participates in Rotavirus Replication.

Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference or inhibiting its activity by treatment with brefeldin A (BFA) or Golgicide A (GCA) significantly reduces the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly, since in the presence of either BFA or GCA, the assembly of infectious mature triple-layered virions was significantly prevented and only double-layered particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface protein VP7, a step required for its incorporation into virus particles. Although a posttranslational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking down its expression reduces VP7 trimerization. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when cotransfected with NSP4.IMPORTANCE Rotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4 and the assembly of the virus surface proteins VP7 and VP4.

Clinical and Laboratory Findings of Barley Allergy in Korean Children: a Single Hospital Based Retrospective Study.

BACKGROUND: Barley is a grain that is consumed in various forms in Asia. Studies on barley allergy are limited to a few case reports about hypersensitivity reactions to beer, but there is no barley allergy study in children. This study aimed to identify the phenotype and immunologic findings in Korean children with barley allergy. METHODS: Forty-two participants with a history of ingesting barley who underwent serum specific immunoglobulin E to barley (barley-sIgE) assay at the Department of Pediatrics in Ajou Medical Center were enrolled through a retrospective analysis of medical records from March 2008 to February 2018. The demographic characteristics, symptoms, and immunologic parameters of the patients were assessed. RESULTS: Twenty subjects presented with clinical barley allergy (B-allergic group), and 22 were atopic controls without allergic reactions after the ingestion of barley (B-tolerant group). The median ages of the B-allergic and B-tolerant groups were 1 and 3 years, respectively. In the B-allergic group, the cutaneous system (90.0%) was most frequently affected, followed by the respiratory system (40.0%). Anaphylaxis was observed in 35.0% of the B-allergic group. The median level of barley-sIgE was 13.90 kUA/L (range, 0.14-101.00 kUA/L) in the B-allergic group, and this value was significantly higher (P < 0.001) than that of the B-tolerant group (0.30 kUA/L; range, 0.01-24.40 kUA/L), with an optimal cutoff level of 1.24 kUA/L (sensitivity, 85.0%; specificity, 86.4%). A positive correlation was found between the serum levels of barley-sIgE and wheat-sIgE in the B-allergic group with clinical wheat allergy. CONCLUSION: Barley is an important allergen for children in Korea. This study showed the clinical characteristics of barley allergy and suggested optimal cut-off levels of barley-sIgE for clinical barley allergy. Clinically, cross-reactivity or co-sensitization is often observed between barley and wheat.

Relative time multiplexing of heralded telecom-band single-photon sources using switchable optical fiber delays.

We experimentally demonstrate a time-multiplexing method for pulse-pumped heralded single-photon sources using switchable optical fiber delay lines. The optical fibers constitute a 32-channel binary-division photon buffer that can multiplex time slots into single temporal mode to enhance single-photon generation rate without increasing multi-photon noise. Relative time multiplexing using the same actively controlled variable delay realizes Hong-Ou-Mandel interferometry by two photons produced in arbitrary two time-bins. The interference dip depth in good agreement with theory verifies path length matching within the photonic coherence length and dispersion compensation of the optical fiber delay sections. We independently confirm by low-coherence interferometry that the internal optical path lengths of the optical switches are constant during the switching operations.

Determinants of nurse absenteeism and intent to leave: An international study.

AIM: To determine factors associated with nurses' intent to leave their positions and absenteeism. BACKGROUND: There is a recognized global shortage of nurses but limited data describing and determining factors associated with nurse absenteeism and intent to leave. METHODS: This study involved a secondary analysis of the results from direct-care registered nurses' responses to the MISSCARE Survey, with data from seven countries included. Multi-level modelling was used to determine nurse characteristics and working environment factors associated with nurse absenteeism and intent to leave. RESULTS: The level of absenteeism and intent to leave varied significantly across countries, with registered nurses in Lebanon reporting the highest intention to leave within 12 months (43%) and registered nurses in Iceland and Australia the highest level of absenteeism (74% and 73%, respectively). Factors associated with outcomes included perceived staffing adequacy of unit, job satisfaction, and age of the nurse. CONCLUSIONS: A significant difference between countries was identified in nurse absenteeism and intent to leave. Increased perception of unit staffing inadequacy, lower job satisfaction, less nurse experience, and younger age were significant contributors to nurse absenteeism and intent to leave. IMPLICATIONS FOR NURSING MANAGEMENT: These findings suggest that regardless of country and hospital, by ensuring that units are adequately staffed and increasing job satisfaction, younger, less experienced nurses can be retained and absenteeism reduced.

Highly conserved motifs within the large Sec7 ARF guanine nucleotide exchange factor GBF1 target it to the Golgi and are critical for GBF1 activity.

Cellular life requires the activation of the ADP-ribosylation factors (ARFs) by Golgi brefeldin A-resistant factor 1 (GBF1), a guanine nucleotide exchange factor (GEF) with a highly conserved catalytic Sec7 domain (Sec7d). In addition to the Sec7d, GBF1 contains other conserved domains whose functions remain unclear. Here, we focus on HDS2 (homology downstream of Sec7d 2) domain because the L1246R substitution within the HDS2 α-helix 5 of the zebrafish GBF1 ortholog causes vascular hemorrhaging and embryonic lethality (13). To dissect the structure/function relationships within HDS2, we generated six variants, in which the most conserved residues within α-helices 1, 2, 4, and 6 were mutated to alanines. Each HDS2 mutant was assessed in a cell-based "replacement" assay for its ability to support cellular functions normally supported by GBF1, such as maintaining Golgi homeostasis, facilitating COPI recruitment, supporting secretion, and sustaining cellular viability. We show that cells treated with the pharmacological GBF1 inhibitor brefeldin A (BFA) and expressing a BFA-resistant GBF1 variant with alanine substitutions of RDR1168 or LF1266 are compromised in Golgi homeostasis, impaired in ARF activation, unable to sustain secretion, and defective in maintaining cellular viability. To gain insight into the molecular mechanism of this dysfunction, we assessed the ability of each GBF1 mutant to target to Golgi membranes and found that mutations in RDR1168 and LF1266 significantly decrease targeting efficiency. Thus, these residues within α-helix 2 and α-helix 6 of the HDS2 domain in GBF1 are novel regulatory determinants that support GBF1 cellular function by impacting the Golgi-specific membrane association of GBF1.

Evaluation of the associations between immunoglobulin E levels and the number of natural teeth.

BACKGROUND/PURPOSE: The purpose of the study was to evaluate the association between the number of natural teeth and the total serum immunoglobulin E (IgE), allergen-specific IgE against Dermatophagoides farina, allergen-specific IgE against cockroaches, or allergen-specific IgE against dogs with nationally representative data using the Korean National Health and Nutrition Examination Survey (KNHANES). METHODS: This study involved a cross-sectional analysis using KNHANES data from 2010. A total of 1916 participants were eligible for this study. Multiple regression analyses were used to evaluate the risk of tooth loss in relation to IgE levels. The model was adjusted for age, sex, body mass index, smoking habits, drinking habits, exercise habits, vitamin D levels, metabolic syndrome, allergic rhinitis, asthma, atopic dermatitis, and tooth-brushing frequency. RESULTS: The number of natural teeth of the first quartile to the fourth quartile of total serum IgE were 25.9 ± 0.2, 25.9 ± 0.2, 25.1 ± 0.2, and 25.4 ± 0.2, respectively, showing an inverse association (P < 0.05). The number of natural teeth of the first quartile to the fourth quartile of allergen-specific IgE against Dermatophagoides farina and allergen-specific IgE against dogs farina both showed an inverse association with statistical significance (P < 0.05). CONCLUSION: This study clearly showed the inverse association between total serum IgE and number of natural teeth after adjustments, especially regarding participants without systemic diseases, including diabetes mellitus, hypertension, metabolic diseases, and obesity.

Melatonin ameliorates alcohol-induced bile acid synthesis by enhancing miR-497 expression.

Alcoholic liver disease is a major cause of chronic liver disease worldwide, and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression. The level of bile acid and the expression of Cb1r, Btg2, Yy1, and bile acid synthetic enzymes were significantly elevated in the livers of Lieber-DeCarli alcohol-fed mice. The overexpression of Btg2 enhanced Yy1 gene expression and bile acid production, whereas disrupting the CB1R-BTG2-YY1 cascade protected against the bile acid synthesis caused by alcohol challenge. We identified an alcohol-mediated YY1 binding site on the cholesterol 7α-hydroxylase (Cyp7a1) gene promoter using promoter deletion analysis and chromatin immunoprecipitation assays. Notably, melatonin attenuated the alcohol-stimulated induction of Btg2, Yy1 mRNA levels and bile acid production by promoting miR-497. Overexpression of a miR-497 mimic dramatically diminished the increase of Btg2 and Yy1 gene expression as well as bile acid production by alcohol, whereas this phenomenon was reversed by miR-497 inhibitor. These results demonstrate that the upregulation of miR-497 by melatonin represses alcohol-induced bile acid synthesis by attenuating the BTG2-YY1 signaling pathway. The melatonin-miR497 signaling network may provide novel therapeutic targets for the treatment of hepatic metabolic dysfunction caused by the alcohol-dependent pathway.