Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome.

NLRP3 forms an inflammasome with its adaptor ASC, and its excessive activation can cause inflammatory diseases. However, little is known about the mechanisms that control assembly of the inflammasome complex. Here we show that microtubules mediated assembly of the NLRP3 inflammasome. Inducers of the NLRP3 inflammasome caused aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme NAD(+), which in turn inactivated the NAD(+)-dependent α-tubulin deacetylase sirtuin 2; this resulted in the accumulation of acetylated α-tubulin. Acetylated α-tubulin mediated the dynein-dependent transport of mitochondria and subsequent apposition of ASC on mitochondria to NLRP3 on the endoplasmic reticulum. Therefore, in addition to direct activation of NLRP3, the creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3 inflammasome.

Vanadium Alkylidyne Initiated Cyclic Polymer Synthesis: The Importance of a Deprotiovanadacyclobutadiene Moiety.

Reported is the catalytic cyclic polymer synthesis by a 3d transition metal complex: a V(V) alkylidyne, [(dBDI)V≡CtBu(OEt2)] (1-OEt2), supported by the deprotonated ß-diketiminate dBDI2- (dBDI2- = ArNC(CH3)CHC(CH2)NAr, Ar = 2,6-iPr2C6H3). Complex 1-OEt2 is a precatalyst for the polymerization of phenylacetylene (PhCCH) to give cyclic poly(phenylacetylene) (c-PPA), whereas its precursor, complex [(BDI)V≡CtBu(OTf)] (2-OTf; BDI- = [ArNC(CH3)]2CH, Ar = 2,6-iPr2C6H3, OTf = OSO2CF3), and the zwitterion [((C6F5)3B-dBDI)V≡CtBu(OEt2)] (3-OEt2) exhibit low catalytic activity despite having a neopentylidyne ligand. Cyclic polymer topologies were verified by size-exclusion chromatography (SEC) and intrinsic viscosity studies. A component of the mechanism of the cyclic polymerization reaction was probed by isolation and full characterization of 4- and 6-membered metallacycles as model intermediates. Metallacyclobutadiene (MCBD) and deprotiometallacyclobutadiene (dMCBD) complexes (dBDI)V[C(tBu)C(H)C(tBu)] (4-tBu) and (BDI)V[C(tBu)CC(Mes)] (5-Mes), respectively, were synthesized upon reaction with bulkier alkynes, tBu- (tBuCCH) and Mes-acetylene (MesCCH), with 1-OEt2. Furthermore, the reaction of the conjugate acid of 1-OEt2, [(BDI)V≡CtBu(OTf)] (2-OTf), with the conjugated base of phenylacetylene, lithium phenylacetylide (LiCCPh), yields the doubly deprotio-metallacycle complex, [Li(THF)4]{(BDI)V[C(Ph)CC(tBu)CC(Ph)]} (6). Protonation of the doubly deprotio-metallacycle complex 6 yields 6-H+, a catalytically active species toward the polymerization of PhCCH, for which the polymers were also confirmed to be cyclic by SEC studies. Computational mechanistic studies complement the experimental observations and provide insight into the mechanism of cyclic polymer growth. The noninnocence of the supporting dBDI2- ligand and its role in proton shuttling to generate deprotiometallacyclobutadiene (dMCBD) complexes that proposedly culminate in the formation of catalytically active V(III) species are also discussed. This work demonstrates how a dMCBD moiety can react with terminal alkynes to form cyclic polyalkynes.

Neonatal head circumference to maternal mid-transverse pelvic distance ratio as a key anatomical predictor for dystocia: Retrospective case-control study.

OBJECTIVE: This study aimed to examine maternal and neonatal factors in cesarean deliveries due to dystocia, including cephalopelvic disproportion, latent-phase prolongation, and fetal malposition or malpresentation. Additionally, we sought to compare the differences between the dystocia subgroups. METHOD AND MATERIALS: This retrospective case-control study included women who delivered between January 2010 and June 2021 after 37 weeks of pregnancy and underwent abdominal-pelvic CT scans within 5 years before and after delivery. Neonatal factors were extracted from medical charts immediately after delivery. RESULTS: Among the 292 women studied, those with cesarean deliveries for dystocia were older (mean ± SD, 34.2 ± 4.27 vs. 32.2 ± 3.8, p-value = 0.002), had higher pre-pregnancy BMI (22.7 ± 3.67 vs. 21.4 ± 3.48, p-value = 0.012) and term-BMI (27.4 ± 3.72 vs. 25.9 ± 3.66, p-value = 0.010), shorter interspinous distance (ISD, the distance between ischial spine) (10.8 ± 0.76 vs. 11.2 ± 0.85 cm, p-value = 0.003), and longer head circumference (HC) (35 ± 1.47 vs. 34.4 ± 1.36 cm, p-value = 0.003) compared to those who had vaginal deliveries. Univariate logistic regression for dystocia revealed associations between HC/maternal height and HC/ISD ratios (OR, 2.02 [95% confidence interval, CI, 1.4 ~ 2.92], 12.13 [3.2 ~ 46.04], respectively). Multivariate logistic analysis indicated that maternal age, ISD, and HC were significant factors for dystocia (OR, 1.11 [95% CI, 1.01 ~ 1.21], 0.49 [0.26 ~ 0.91], 1.53 [1.07 ~ 2.19], respectively). The subgroup with latent-phase prolongation exhibited the lowest birthweight/term-BMI ratio (124 ± 18.8 vs. 113 ± 10.3 vs. 134 ± 19.1, p-value = 0.013). CONCLUSION: The HC/ISD ratio emerged as a crucial predictor of dystocia, suggesting that reducing term-BMI could potentially mitigate latent-phase prolongation. Further research assessing the maternal mid-pelvis during pregnancy and labor is warranted, along with efforts to reduce BMI during pregnancy.

Development and evaluation of extracorporeal membrane oxygenation nursing education program for nursing students using virtual reality.

BACKGROUND: This study aims to improve nursing students' ability to care for critically ill patients through education in extracorporeal membrane oxygenation (ECMO) nursing. METHODS: This study developed a virtual reality (VR) simulation program for the five-step ECMO nursing of the Analysis, Design, Development, Implement, and Evaluation (ADDIE) model and used an equivalent control group pre-test and post-test no-synchronized design to verify the effect. The participants of this study were fourth-year nursing students enrolled in nursing departments at three universities in Seoul, Gangwon, and Gyeonggi in South Korea; it included 66 participants, 33 in each of the experimental and control groups. The program consisted of pre-training, orientation, VR simulation, and debriefing. RESULTS: The interaction effect of the intervention and control groups with time points using the ECMO nursing VR simulation program was rejected due to no statistically significant difference in knowledge (F = 1.41, p = .251), confidence (F = 1.97, p = .144), and clinical reasoning capacity (F = 2.85, p = .061). However, learning immersion (t = 3.97, p < .001) and learning satisfaction (t = 4.25, p < .001) were statistically significantly higher in the experimental group than in the control group. CONCLUSION: VR simulation program for ECMO nursing developed in this study is a potential educational method that positively affects the learning immersion and learning satisfaction of nursing students.

Highly Enantioselective 6π Photoelectrocyclizations Engineered by Hydrogen Bonding.

Photochemical electrocyclization reactions are valued for both their ability to produce structurally complex molecules and their central role in elucidating fundamental mechanistic principles of photochemistry. We present herein a highly enantioselective 6π photoelectrocyclization catalyzed by a chiral Ir(III) photosensitizer. This transformation was successfully realized by engineering a strong hydrogen-bonding interaction between a pyrazole moiety on the catalyst and a basic imidazolyl ketone on the substrate. To shed light on the origin of stereoinduction, we conducted a comprehensive investigation combining experimental and computational mechanistic studies. Results from density functional theory calculations underscore the crucial role played by the prochirality and the torquoselectivity in the electrocyclization process as well as the steric demand in the subsequent [1,4]-H shift step. Our findings not only offer valuable guidance for developing chiral photocatalysts but also serve as a significant reference for achieving high levels of enantioselectivity in the 6π photoelectrocyclization reaction.

Climate-ecosystem modelling made easy: The Land Sites Platform.

Dynamic Global Vegetation Models (DGVMs) provide a state-of-the-art process-based approach to study the complex interplay between vegetation and its physical environment. For example, they help to predict how terrestrial plants interact with climate, soils, disturbance and competition for resources. We argue that there is untapped potential for the use of DGVMs in ecological and ecophysiological research. One fundamental barrier to realize this potential is that many researchers with relevant expertize (ecology, plant physiology, soil science, etc.) lack access to the technical resources or awareness of the research potential of DGVMs. Here we present the Land Sites Platform (LSP): new software that facilitates single-site simulations with the Functionally Assembled Terrestrial Ecosystem Simulator, an advanced DGVM coupled with the Community Land Model. The LSP includes a Graphical User Interface and an Application Programming Interface, which improve the user experience and lower the technical thresholds for installing these model architectures and setting up model experiments. The software is distributed via version-controlled containers; researchers and students can run simulations directly on their personal computers or servers, with relatively low hardware requirements, and on different operating systems. Version 1.0 of the LSP supports site-level simulations. We provide input data for 20 established geo-ecological observation sites in Norway and workflows to add generic sites from public global datasets. The LSP makes standard model experiments with default data easily achievable (e.g., for educational or introductory purposes) while retaining flexibility for more advanced scientific uses. We further provide tools to visualize the model input and output, including simple examples to relate predictions to local observations. The LSP improves access to land surface and DGVM modelling as a building block of community cyberinfrastructure that may inspire new avenues for mechanistic ecosystem research across disciplines.

Self-Scheduled LPV Control of Asymmetric Variable-Span Morphing UAV.

In this study, a novel framework for the flight control of a morphing unmanned aerial vehicle (UAV) based on linear parameter-varying (LPV) methods is proposed. A high-fidelity nonlinear model and LPV model of an asymmetric variable-span morphing UAV were obtained using the NASA generic transport model. The left and right wing span variation ratios were decomposed into symmetric and asymmetric morphing parameters, which were then used as the scheduling parameter and the control input, respectively. LPV-based control augmentation systems were designed to track the normal acceleration, angle of sideslip, and roll rate commands. The span morphing strategy was investigated considering the effects of morphing on various factors to aid the intended maneuver. Autopilots were designed using LPV methods to track commands for airspeed, altitude, angle of sideslip, and roll angle. A nonlinear guidance law was coupled with the autopilots for three-dimensional trajectory tracking. A numerical simulation was performed to demonstrate the effectiveness of the proposed scheme.

Development and evaluation of a virtual reality mechanical ventilation education program for nursing students.

BACKGROUND: Since COVID-19 limits safe clinical practice settings, virtual reality (VR) emerged as an alternative to practical education. Using VR simulation to learn mechanical ventilation is rare in nursing education. METHODS: This study developed a VR simulation program for mechanical ventilation care and evaluated its effects. We adopted a quasi-experiment design. Participants were fourth-year students across nursing colleges in South Korea. RESULTS: The interaction effect of the intervention time point and control group, to which the VR simulation program was applied, showed a significant difference in self-efficacy (F = 19.54, p < .001) and clinical reasoning capacity (F = 16.97, p < .001). Learning satisfaction of the experimental group was statistically significantly higher than that of the control group(F = 5.22, p = .026). The level of learning immersion (t = - 3.13, p = .003) and learning satisfaction (t = - 3.49, p = .001) were statistically significantly higher in the experimental group than in the control group. CONCLUSION: These findings confirmed that the VR stimulation program for nursing students had a positive effect on their self-efficacy, clinical reasoning capacity, and learning satisfaction. Furthermore, it was effective in improving their nursing competence.

Analysis of the effect of an artificial intelligence chatbot educational program on non-face-to-face classes: a quasi-experimental study.

BACKGROUND: Education and training are needed for nursing students using artificial intelligence-based educational programs. However, few studies have assessed the effect of using chatbots in nursing education. OBJECTIVES: This study aimed to develop and examine the effect of an artificial intelligence chatbot educational program for promoting nursing skills related to electronic fetal monitoring in nursing college students during non-face-to-face classes during the COVID-19 pandemic. DESIGN: This quasi-experimental study used a nonequivalent control group non-synchronized pretest-posttest design. METHODS: The participants were 61 junior students from a nursing college located in G province of South Korea. Data were collected between November 3 and 16, 2021, and analyzed using independent t-tests. RESULTS: The experimental group-in which the artificial intelligence chatbot program was applied-did not show statistically significant differences in knowledge (t = -0.58, p = .567), clinical reasoning competency (t = 0.75, p = .455), confidence (t = 1.13, p = .264), and feedback satisfaction (t = 1.72, p = .090), compared with the control group; however, its participants' interest in education (t = 2.38, p = .020) and self-directed learning (t = 2.72, p = .006) were significantly higher than those in the control group. CONCLUSION: The findings of our study highlighted the potential of artificial intelligence chatbot programs as an educational assistance tool to promote nursing college students' interest in education and self-directed learning. Moreover, such programs can be effective in enhancing nursing students' skills in non-face-to face-situations caused by the ongoing COVID-19 pandemic.

pH-Responsive Inorganic/Organic Nanohybrids System for Controlled Nicotinic Acid Drug Release.

Although nicotinic acid (NA) has several clinical benefits, its potency cannot be fully utilized due to several undesirable side effects, including cutaneous flushing, GIT-associated symptoms, etc. To overcome such issues and improve the NA efficacy, a new inorganic-organic nanohybrids system was rationally designed. For making such a hybrid system, NA was intercalated into LDH through a coprecipitation technique and then coated with Eudragit® S100 to make the final drug delivery system called Eudragit® S100-coated NA-LDH. The as-made drug delivery system not only improved the NA release profile but also exhibited good bio-compatibility as tested on L929 cells. Such an inorganic-organic nanohybrid drug delivery agent is expected to reduce the undesirable side effects associated with NA and hopefully improve the pharmacological effects without inducing any undesirable toxicity.

Artificial cell factory design for shikimate production in Escherichia coli.

Shikimate is a key intermediate in high demand for synthesizing valuable antiviral drugs, such as the anti-influenza drug and oseltamivir (Tamiflu®). Microbial-based shikimate production strategies have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. Although shikimate biosynthesis has been reported in several engineered bacterial species, the shikimate production yield is still unsatisfactory. This study designed an Escherichia coli cell factory and optimized the fed-batch culture process to achieve a high titer of shikimate production. Using the previously constructed dehydroshikimate (DHS)-overproducing E. coli strain, two genes (aroK and aroL) responsible for converting shikimate to the next step were disrupted to facilitate shikimate accumulation. The genes with negative effects on shikimate biosynthesis, including tyrR, ptsG, and pykA, were disrupted. In contrast, several shikimate biosynthetic pathway genes, including aroB, aroD, aroF, aroG, and aroE, were overexpressed to maximize the glucose uptake and intermediate flux. The shiA involved in shikimate transport was disrupted, and the tktA involved in the accumulation of both PEP and E4P was overexpressed. The rationally designed shikimate-overproducing E. coli strain grown in an optimized medium produced approximately 101 g/l of shikimate in 7-l fed-batch fermentation, which is the highest level of shikimate production reported thus far. Overall, rational cell factory design and culture process optimization for microbial-based shikimate production will play a key role in complementing traditional plant-derived shikimate production processes.

Glucose in a maturation medium with reduced NaCl improves oocyte maturation and embryonic development after somatic cell nuclear transfer and in vitro fertilization in pigs.

This study was conducted to examine whether glucose in maturation medium containing reduced NaCl could improve oocyte maturation and embryonic development in pigs. The base medium was bovine serum albumin-free porcine zygote medium (PZM)-3 containing 10% (v/v) pig follicular fluid (FPZM) or 0.1% (w/v) polyvinyl alcohol (PPZM). Using each medium, the effects of NaCl concentrations (108 and 61.6 mM) and 5.56 mM glucose supplementation (designated as PZM108N, PZM108G, PZM61N, and PZM61G, respectively) were examined using a 2 × 2 factorial arrangement. When oocytes were matured in FPZM, glucose supplementation improved nuclear maturation compared with no supplementation, regardless of the NaCl concentrations. FPZM61G showed a higher blastocyst formation compared with FPZM108N and FPZM108G after parthenogenesis (PA). Blastocyst formations of somatic cell nuclear transfer (SCNT) embryos derived from FPZM61N and FPZM61G were higher compared with those of oocytes from FPZM108N. When oocytes were matured in PPZM, glucose added to PPZM108 and PPZM61 increased nuclear maturation compared with no supplementation. However, glucose added to PPZM108 did not alter embryonic development after PA. Additionally, oocytes matured in PPZM61G showed a higher blastocyst formation compared with those from PPZM61N. In SCNT, blastocyst formation was not influenced by glucose supplementation of PPZM108, but was increased by maturation in glucose-supplemented PPZM61. In embryonic development of in vitro fertilization (IVF), oocytes matured in medium with reduced NaCl and glucose showed significantly higher blastocyst formation compared with those matured in PPZM108G. Our results demonstrated that glucose in maturation medium containing 61.6 mM NaCl increased oocyte maturation and embryonic development after PA, SCNT, and IVF.

A 3D Printable Electroconductive Biocomposite Bioink Based on Silk Fibroin-Conjugated Graphene Oxide.

Reduced graphene oxide (rGO) has wide application as a nanofiller in the fabrication of electroconductive biocomposites due to its exceptional properties. However, the hydrophobicity and chemical stability of rGO limit its ability to be incorporated into precursor polymers for physical mixing during biocomposite fabrication. Moreover, until now, no suitable rGO-combining biomaterials that are stable, soluble, biocompatible, and 3D printable have been developed. In this study, we fabricated digital light processing (DLP) printable bioink (SGOB1), through covalent reduction of graphene oxide (GO) by glycidyl methacrylated silk fibroin (SB). Compositional analyses showed that SGOB1 contains approximately 8.42% GO in its reduced state. Our results also showed that the rGO content of SGOB1 became more thermally stable and highly soluble. SGOB1 hydrogels demonstrated superior mechanical, electroconductive, and neurogenic properties than (SB). Furthermore, the photocurable bioink supported Neuro2a cell proliferation and viability. Therefore, SGOB1 could be a suitable biocomposite for neural tissue engineering.

Optical and Fluorescent Dual Sensing of Aminoalcohols by in Situ Generation of BODIPY-like Chromophore.

A novel multifunctional aminophenylboronic acid connected to a diphenylketone gives both circular dichroism and fluorescence signals by in situ generation of a BODIPY-like chromophore in the presence of aminoalcohols. DFT calculations were used to understand the role of each functional group in the mechanism. This new sensor can distinguish different aminoalcohols and quantitatively indicate the concentration of the substrate, allowing for the convenient determination of the ee of racemic mixtures with a single probe.

Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy.

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.

Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly inflammatory autoimmune disease. Although proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-6, play a key role in the pathogenesis of RA, the causes of chronic inflammation are not fully understood. Here, we report that protein phosphatase magnesium-dependent 1A (PPM1A) levels were increased in RA synovial fluid compared with osteoarthritis (OA) synovial fluid and positively correlated with TNF levels. In addition, PPM1A expression was increased in synovial tissue from RA patients and joint tissue from a mouse model of arthritis. Finally, extracellular PPM1A induced inflammation by stimulating macrophages to produce TNF through toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) signaling pathway. Our findings suggest that extracellular PPM1A may contribute to the pathogenesis of RA by functioning as a damage-associated molecular pattern (DAMP) to induce inflammation.

Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer.

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.

Actor and partner effects of parenting stress and co-parenting on marital conflict among parents of children with atopic dermatitis.

BACKGROUND: It is important for healthcare providers to pay attention to parents' rearing style and children's physical symptoms to promote a healthy quality of life among children with atopic dermatitis. We aimed to identify effects of parenting stress and co-parenting on marital conflict among parents of children with atopic dermatitis. METHODS: Participants were 161 fathers and 161 mothers raising seven-year-old children treated for atopic dermatitis. To confirm the effects of parenting stress and co-parenting on marital conflict, the "actor-partner interdependence mediation model" was used. To verify goodness-of-fit, maximum likelihood method was used, and a confirmatory factor analysis was conducted to confirm the validity of latent variables for model analysis. RESULTS: Fathers' parenting stress had actor (ß = -.46, p < .001) and partner (ß = -.22, p < .001) effects on co-parenting, and mothers' parenting stress had actor (ß = -.20, p < .001) and partner (ß = -.36, p < .001) effects on co-parenting. Fathers' parenting stress only had an actor effect on marital conflict (ß = .32, p < .001). Father's co-parenting had actor (ß = -.29, p < .001) and partner (ß = -.22, p < .001) effects on marital conflict, and mothers' co-parenting had actor (ß = -.39, p < .001) and partner (ß = -.19, p < .001) effects on marital conflict. There were significant differences between the two groups concerning three path coefficients: fathers' parenting stress affected fathers' marital conflict, fathers' co-parenting affected fathers' marital conflict, and mothers' co-parenting affected fathers' marital conflict. CONCLUSIONS: It is vital for healthcare providers to seek ways to reduce the marital conflicts of parents of children with atopic dermatitis, including further examination of the role of co-parenting, to address children's physical symptoms and promote their health. Our findings inform management and intervention programs for the families of children with atopic dermatitis.

A Phytochemical Constituent, (E)-Methyl-Cinnamate Isolated from Alpinia katsumadai Hayata Suppresses Cell Survival, Migration, and Differentiation in Pre-Osteoblasts.

BACKGROUND: (E)-methyl-cinnamate (EMC), a phytochemical constituent isolated from Alpinia katsumadai Hayata, is a natural flavor compound with anti-inflammatory properties, which is widely used in the food and commodity industry. However, the pharmacological effects of methyl-cinnamate on pre-osteoblasts remain unknown. This study aimed to investigate the pharmacological effects and mechanisms of EMC in pre-osteoblast MC3T3-E1 cells (pre-osteoblasts). METHODS: Cell viability and apoptosis were evaluated using the MTT assay and TUNEL staining. Cell migration and osteoblast differentiation were examined using migration assays, as well as alkaline phosphatase activity and staining assays. Western blot analysis was used to examine intracellular signaling pathways and apoptotic proteins. RESULTS: EMC decreased cell viability with morphological changes and increased apoptosis in pre-osteoblasts. EMC also induced the cleavage of Poly (ADP-ribose) polymerase (PARP) and caspase-3 and reduced the expression of anti-apoptotic proteins. In addition, EMC increased TUNEL-positive cells in pre-osteoblasts, decreased the activation of mitogen-activated protein kinases, and suppressed cell migration rate in pre-osteoblasts. Subsequently, EMC inhibited the osteoblast differentiation of pre-osteoblasts, as assessed by alkaline phosphatase staining and activity assays. CONCLUSION: These findings demonstrate that EMC has a pharmacological and biological role in cell survival, migration, and osteoblast differentiation. It suggests that EMC might be a potential phytomedicine for treating abnormalities of osteoblast function in bone diseases.

The effects of hardcore smokers' depression and self-esteem on daily smoking amount.

BACKGROUND: This is a secondary data analysis designed as a longitudinal study aimed at investigating the effects of depression and self-esteem on daily smoking amounts among hardcore smokers over time. METHODS: The subjects of this study were 264 hardcore smokers aged 19 years or older who participated in all waves of the 9th-13th Korea Welfare Panel Studies. Self-report questionnaires were used to collect data. Data analyses were performed using SPSS WIN 24.0 and AMOS 18.0, and data were analyzed using a latent growth model. RESULTS: The intercept of depression and self-esteem among the subjects had statistically significant effects on the intercept of the daily smoking amount. The slope of depression and self-esteem among the subjects also had statistically significant effects on the slope of the daily smoking amount. The slope of depression indirect affected the slope of daily smoking amount via the level of self-esteem. CONCLUSION: It is important to determine the initial levels and the rates of change of depression, self-esteem, and daily smoking amount among hardcore smokers. In order to reduce the daily smoking amount among hardcore smokers, interventions for depression and methods to improve self-esteem among hardcore smokers should be considered.