The smallest Schwarzite carbon with only heptagonal carbon rings.

Carbon materials with full sp2-hybridized buckling is a major challenge pervading fundamental nanoscience and nanotechnology research. Carbon atoms that are sp2 hybridized prefer to form hexagonal rings, such as in carbon nanotubes and graphene, which are low-dimensional materials. The incorporation of heptagonal, octagonal, and/or larger rings into a hexagonal sp2 carbon meshwork has been identified as a strategy for assembling three-dimensional (3D) sp2 carbon crystals, and one of the typical representatives are Schwarzite carbons, which possess a negative surface Gaussian curvature as well as unique physical properties. Herein, a 3D Schwarzite carbon consisting of only sp2-buckled heptagonal carbon rings, which is referred to as Hepta-carbon, is proposed based on first-principles calculations. Hepta-carbon is mechanically and thermodynamically stable, and energetically more favourable than experimental graphdiyne, fullerene C20 and most Schwarzite carbons under ambient conditions. Molecular dynamics simulations indicate that Hepta-carbon exhibits high-temperature thermostability up to 1500 K. Band structure and mechanical property simulations indicate that Hepta-carbon is a semi-metallic material with electron conduction and exhibits impressive mechanical properties such as high strength with quasi-isotropy, high incompressibility similar to diamonds, elastic deformation behaviour under uniaxial stress, and high ductility. Hepta-carbon presents a porous network with a low mass density of 1.84 g cm-3 and connected channels with diameters of 3.3-6.1 Å. Theoretical simulations of gas adsorption energy demonstrate that Hepta-carbon can effectively adsorb and stabilize greenhouse gases, including N2O, CO2, CH4, and SF6.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study.

BACKGROUND: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. METHODS: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. RESULTS: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83-0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72-0.83). CONCLUSION: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Neurocognitive changes at different follow-up times after bilateral subthalamic nucleus deep brain stimulation in patients with Parkinson's disease.

Background: Bilateral deep thalamic nucleus brain stimulation (STN-DBS) surgery is often used to treat the motor symptoms of patients with Parkinson's disease. The change of neurocognitive symptoms in patients is, however, still unclear. Objective: We aimed at analyzing the deterioration of neurocognitive symptoms in patients with Parkinson's disease after deep brain stimulation surgery under different follow-up times. Methods: A comprehensive literature review was conducted using Pubmed, Cochrane Library, and Web of Science to screen eligible study records, the meta-analysis was performed using an inverse variance method and a random-effects model. Additionally, the areas of analysis include five: cognition, executive function, memory capacity, and verbal fluency (phonetic fluency and semantic fluency). They were analyzed for changes at six and twelve months postoperatively compared to baseline. The Meta-analysis has been registered with PROSPERO under the registration number: CRD42022308786. Results: In terms of overall cognitive performance, executive function, and memory capacity, the original studies show a trend of improvement in these areas at 12 months postoperatively compared with 6 months, at variance, patients did not improve or deteriorated in phonetic fluency(d = -0.42 at both 6-month and 12-month follow-up) and semantic fluency from 6 to 12 months postoperatively. Conclusion: In terms of most neurocognitive symptoms, including cognitive ability, executive function, and learning memory capacity, bilateral STN-DBS surgery appears to be safe at relatively long follow-up times. However, postoperative phonetic and semantic fluency changes should still not be underestimated, and clinicians should pay more attention to patients' changes in both.

A Low Eosinophil to Platelet Ratio as a Worse Prognostic Index for Emergency Department Attendance in Acute Exacerbation of COPD.

Purpose: Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department. Patients and Methods: The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated. Results: A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR <0.755, exacerbation history, PaO2 <60mmHg, PaCO2 >50 mm Hg, hypoalbuminemia and age ≥80 was developed to predict death risk and showed good performance. Conclusion: During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.

Change in neighborhood socioeconomic status and childhood weight status and body composition from birth to adolescence.

BACKGROUND: We aim to assess the associations between the change in neighborhood socioeconomic score (SES) between birth and 6 years and childhood weight status and body composition from 6 to 13 years. METHODS: Data for 3909 children from the Generation R Study, a prospective population-based cohort in the Netherlands were analyzed. The change in neighborhood SES between birth and 6 years was defined as static-high, static-middle, static-low, upward, and downward mobility. Child body mass index (BMI), overweight and obesity (OWOB), fat mass index (FMI) and lean mass index (LMI) were measured at age 6, 10, and 13 years. The associations were explored using generalized estimating equations. The effect modification by child sex was examined. RESULTS: In total, 19.5% and 18.1% of children were allocated to the upward mobility and downward mobility neighborhood SES group. The associations between the change in neighborhood SES and child weight status and body composition were moderated by child sex (p < 0.05). Compared to girls in the static-high group, girls in the static-low group had relatively higher BMI-SDS (ß, 95% confidence interval (CI): 0.24, 0.09-0.40) and higher risk of OWOB (RR, 95% CI: 1.98, 1.35-2.91), together with higher FMI-SDS (ß, 95% CI: 0.27, 0.14-0.41) and LMI-SDS (ß, 95% CI: 0.18, 0.03-0.33). The associations in boys were not significant. CONCLUSIONS: An increased BMI and fat mass, and higher risk of OWOB from 6 to 13 years were evident in girls living in a low-SES neighborhood or moving downward from a high- to a low-SES neighborhood. Support for children and families from low-SES neighborhoods is warranted.

Physical activity, screen time and body composition in 13-year-old adolescents: The Generation R Study.

BACKGROUND: Body composition between prepubertal children and adolescents varies, and it is unclear how physical activity and sedentary behaviour affect adolescent body composition. OBJECTIVES: This study aimed to examine the associations of physical activity and screen time with overall and specific fat depots in the general adolescent population. METHODS: In a population-based prospective cohort study, among 3258 adolescents aged 13 years, physical activity and screen time were assessed via self-report questionnaires. Body mass index, dual-energy X-ray absorptiometry-based measures (i.e. fat mass and lean body mass) and magnetic resonance imaging-based measures (i.e. abdominal subcutaneous and visceral fat mass) were obtained. RESULTS: After adjusting for social-demographic and growth-related factors, each additional hour of daily physical activity was associated with lower fat mass, abdominal visceral fat mass and higher lean body mass (all p < 0.05). However, these associations were not observed in the longitudinal analyses. Each additional hour of daily screen time was associated with higher body mass index, fat mass, abdominal subcutaneous and visceral fat mass (all p < 0.05), which were consistent with the longitudinal analyses. CONCLUSION: Adolescents with higher physical activity and lower screen time had lower levels of adiposity both at the general and visceral levels.

Multidimensional energy poverty and acute respiratory infection in children under 5 years of age: evidence from 22 low-income and middle-income countries.

BACKGROUND: In low-income and middle-income countries (LMICs), energy poverty has predominantly been studied from the unidimensional perspective of indoor air pollution. Acute respiratory infection (ARI) in children under 5 years of age is the most important disease associated with indoor air pollution attributable to solid fuel use in LMICs. This study aimed to extend the existing knowledge on the association between energy poverty and ARI among children under 5 years of age in LMICs, by adopting a multidimensional perspective. METHODS: Using Demographic and Health Surveys from 22 LMICs, data from 483 088 children were analysed (mean age 2.00 years (SD 1.41); 51.3% male). Energy poverty was measured using the Multidimensional Energy Poverty Index (MEPI) (range 0-1), which comprises five dimensions of essential energy services. Binary logistic regression models were conducted to study the association between MEPI and ARI, adjusting for child, maternal, household and environmental characteristics. RESULTS: A 0.1 increase in MEPI score was associated with greater odds of ARI (aOR 1.05; 95% CI 1.04 to 1.07). Likewise, MEPI indicators using biomass for cooking (aOR 1.15; 95% CI 1.07 to 1.23) and lack of access to electricity (aOR 1.17; 95% CI 1.10 to 1.26), entertainment/education appliances (aOR 1.07; 95% CI 1.02 to 1.13) and household appliances (aOR 1.12; 95% CI 1.04 to 1.21) were associated with greater odds of ARI. CONCLUSION: Multidimensional energy poverty was associated with greater odds of ARI in children under 5 years of age living in 22 LMICs. Hence, our findings justify the design and implementation of interventions that address energy poverty from a multidimensional perspective, integrating energy affordability and accessibility.

Mitoquinone ameliorated airway inflammation by stabilizing ß-catenin destruction complex in a steroid-insensitive asthma model.

BACKGROUND AND PURPOSE: Mitochondrial dysfunction is an essential part of the pathophysiology of asthma, and potential treatments that target the malfunctioning mitochondria have attracted widespread attention. We have previously demonstrated that aberrant epithelial ß-catenin signaling played a crucial role in a toluene diisocyanate (TDI)-induced steroid-insensitive asthma model. The objective of this study was to determine if the mitochondrially targeted antioxidant mitoquinone(MitoQ) regulated the activation of ß-catenin in TDI-induced asthma. METHOD: Mice were sensitized and challenged with TDI to generate a steroid-insensitive asthma model. Human bronchial epithelial cells (16HBE) were exposed to TDI-human serum albumin (HSA) and ethidium bromide(EB) to simulate the TDI-induced asthma model and mitochondrial dysfunction. RESULTS: MitoQ dramatically attenuated TDI-induced AHR, airway inflammation, airway goblet cell metaplasia, and collagen deposition and markedly protected epithelial mitochondrial functions by preserving mass and diminishing the production of reactive oxygen species (ROS). MitoQ administration stabilized ß-catenin destruction complex from disintegration and inhibited the activation of ß-catenin. Similarly, YAP1, an important constituent of ß-catenin destruction complex, was inhibited by Dasatinib, which alleviated airway inflammation and the activation of ß-catenin, and restored mitochondrial mass. In vitro, treating 16HBE cells with EB led to the activation of YAP1 and ß-catenin signaling, decreased the expression of glucocorticoid receptors and up-regulated interleukin (IL)-1ß, IL6 and IL-8 expression. CONCLUSION: Our results indicated that mitochondria mediates airway inflammation by regulating the stability of the ß-catenin destruction complex and MitoQ might be a promising therapeutic approach to improve airway inflammation and severe asthma. AVAILABILITY OF DATA AND MATERIALS: The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Neurobiological, Psychosocial, and Behavioral Mechanisms Mediating Associations Between Physical Activity and Psychiatric Symptoms in Youth in the Netherlands.

Importance: Understanding the mechanisms by which physical activity is associated with a lower risk of psychiatric symptoms may stimulate the identification of cost-efficient strategies for preventing and treating mental illness at early life stages. Objective: To examine neurobiological, psychosocial, and behavioral mechanisms that mediate associations of physical activity with psychiatric symptoms in youth by testing an integrated model. Design, setting, and participants: Generation R is an ongoing prospective population-based cohort study collecting data from fetal life until young adulthood in a multiethnic urban population in the Netherlands. Pregnant women living in Rotterdam with an expected delivery date between April 2002 and January 2006 were eligible for participation along with their children born during this time. Data were collected at a single research center in the Erasmus Medical Center Sophia Children's Hospital. For the current study, data were analyzed from 4216 children with complete data on both exposure and outcome at ages 6, 10, and 13 years. Data were analyzed from January 2021 to November 2022. Exposures: Physical activity was ascertained at age 6 years (visit 1) via parent report and included weekly frequency and duration of walking or cycling to or from school, physical education at school, outdoor play, swimming, and sports participation. Main Outcomes and Measures: Psychiatric symptoms (internalizing and externalizing symptoms) were assessed at age 6 years (visit 1) and at age 13 years (visit 3) using the Child Behavior Checklist. Several mechanisms were explored as mediators, measured at age 10 years (visit 2). Neurobiological mechanisms included total brain volume, white matter microstructure, and resting-state connectivity assessed using a 3-T magnetic resonance imaging scanner. Psychosocial mechanisms included self-esteem, body image, and friendship. Behavioral mechanisms included sleep quality, diet quality, and recreational screen time. Pearson correlations between physical activity measures and psychiatric symptoms were calculated, with false discovery rate correction applied to account for the number of tests performed. Mediation analyses were performed when a correlation (defined as false discovery rate P < .05) between exposure and outcome was observed and were adjusted for confounders. Results: Among the 4216 children included in this study, the mean (SD) age was 6.0 (0.4) years at visit 1, and 2115 participants (50.2%) were girls. More sports participation was associated with fewer internalizing symptoms (ß for direct effect, -0.025; SE, 0.078; P = .03) but not externalizing symptoms. Self-esteem mediated the association between sports participation and internalizing symptoms (ß for indirect effect, -0.009; SE, 0.018; P = .002). No evidence was found for associations between any other neurobiological, psychosocial, or behavioral variables. No association was found between other types of physical activity and psychiatric symptoms at these ages. Conclusions and Relevance: The integrated model presented in this cohort study evaluated potential mechanisms mediating associations between physical activity and psychiatric symptoms in youth. Self-esteem mediated an association between sports participation in childhood and internalizing symptoms in adolescence; other significant mediations were not observed. Further studies might explore whether larger effects are present in certain subgroups (eg, children at high risk of developing psychiatric symptoms), different ages, or structured sport-based physical activity interventions.

The association between frailty and the risk of medication-related problems among community-dwelling older adults in Europe.

BACKGROUND: Studies revealed unidirectional associations between frailty and medication-related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi-directional association between frailty and the risk of MRPs in community-dwelling older adults in five European countries. METHODS: Participants were 1785 older adults in the population-based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one-year follow-up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross-lagged panel modeling was used to assess bi-directional associations. RESULTS: The unidirectional association between frailty at baseline and the risk of MRPs at follow-up remained statistically significant after adjusting for covariates (ß = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow-up shows similar trends. The bi-directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow-up than reversed path (Wald test for comparing lagged effects: p < 0.05). CONCLUSION: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways.

Genome-Wide Association Study in Acute Tubulointerstitial Nephritis.

SIGNIFICANCE STATEMENT: Polymorphisms of HLA genes may confer susceptibility to acute tubulointerstitial nephritis (ATIN), but small sample sizes and candidate gene design have hindered their investigation. The first genome-wide association study of ATIN identified two significant loci, risk haplotype DRB1*14-DQA1*0101-DQB1*0503 (DR14 serotype) and protective haplotype DRB1*1501-DQA1*0102-DQB1*0602 (DR15 serotype), with amino acid position 60 in the peptide-binding groove P10 of HLA-DR ß 1 key. Risk alleles were shared among different causes of ATIN and HLA genotypes associated with kidney injury and immune therapy response. HLA alleles showed the strongest association. The findings suggest that a genetically conferred risk of immune dysregulation is part of the pathogenesis of ATIN. BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare immune-related disease, accounting for approximately 10% of patients with unexplained AKI. Previous elucidation of the relationship between genetic factors that contribute to its pathogenesis was hampered because of small sample sizes and candidate gene design. METHODS: We undertook the first two-stage genome-wide association study and meta-analysis involving 544 kidney biopsy-defined patients with ATIN and 2346 controls of Chinese ancestry. We conducted statistical fine-mapping analysis, provided functional annotations of significant variants, estimated single nucleotide polymorphism (SNP)-based heritability, and checked genotype and subphenotype correlations. RESULTS: Two genome-wide significant loci, rs35087390 of HLA-DQA1 ( P =3.01×10 -39 ) on 6p21.32 and rs2417771 of PLEKHA5 on 12p12.3 ( P =2.14×10 -8 ), emerged from the analysis. HLA imputation using two reference panels suggested that HLA-DRB1*14 mainly drives the HLA risk association . HLA-DRB1 residue 60 belonging to pocket P10 was the key amino acid position. The SNP-based heritability estimates with and without the HLA locus were 20.43% and 10.35%, respectively. Different clinical subphenotypes (drug-related or tubulointerstitial nephritis and uveitis syndrome) seemed to share the same risk alleles. However, the HLA risk genotype was associated with disease severity and response rate to immunosuppressive therapy. CONCLUSIONS: We identified two candidate genome regions associated with susceptibility to ATIN. The findings suggest that a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.

Blockade of neutrophil extracellular traps ameliorates toluene diisocyanate-induced steroid-resistant asthma.

BACKGROUND AND PURPOSE: Toluene diisocyanate (TDI)-induced asthma is characterized by mixed inflammation dominated by neutrophils, and is refractory to steroid treatment. Neutrophil extracellular traps (NETs) play an important role in severe asthma, but their role in TDI-induced asthma models is unclear. This study focused on the role and mechanism of NETs in steroid-resistant TDI-induced asthma. METHODS: Induced sputum was collected from 85 asthmatic patients and 25 healthy controls to detect eDNA. A murine TDI-induced asthma model was prepared, and asthmatic mice were given dexamethasone or DNase I. In vitro, the human bronchial epithelial cell line HBE was stimulated with NETs or TDI-human serum albumin (TDI-HSA). RESULTS: Asthma patients had higher sputum eDNA compared to healthy subjects. In asthma patients, eDNA was positively correlated with sputum neutrophils, and negatively correlated with FEV1%predicted. Airway inflammation, airway reactivity, Th2 cytokine levels in lymph supernatant, and levels of NETs were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by DNase I, but not by dexamethasone. Inhibition of NETs improved interleukin (IL)-8 and MKP1 mRNA expression, and reduced phosphorylation of GR-S226 induced by TDI. Inhibition of NETs improved airway epithelial barrier disruption, as well as p38 and ERK signaling pathways in TDI-induced asthmatic mice. In vitro, NETs promoted the expression of IL-8 mRNA in HBE cells, and reduced the expression of MKP1. IL-8 elevation induced by NETs was suppressed by a p38 inhibitor or ERK inhibitor, but not by dexamethasone. Pretreatment with RAGE inhibitor reduced NETs induced p38/ERK phosphorylation and IL-8 levels in HBE cells. CONCLUSION: Our data suggest that targeting NETs might effectively improved TDI-induced airway inflammation and airway epithelial barrier function. This may potentially be a treatment for patients with steroid-resistance asthma.

Factors of heavy social media use among 13-year-old adolescents on weekdays and weekends.

BACKGROUND: Few studies have investigated which factors were related to adolescents' social media use. This study aimed to evaluate which factors were associated with heavy social media use on weekdays and weekends among 13-year-old adolescents. METHODS: We analyzed data from 3727 children from the Generation R Study, a population-based cohort study in the Netherlands. Associations of demographic factors (child age, sex, ethnic background, and family situation), socioeconomic position (parental educational level, parental employment status, and net household income), screen-based behaviors (computer playing and TV viewing), and the home environment (communication, supervision, and restriction) with adolescents' heavy social media use (≥ 2 hours/day) were assessed separately on weekdays and weekends. Multivariate logistic regression analysis was applied. RESULTS: The prevalence of heavy social media use was 37.7% on a weekday and 59.6% on a weekend day. Being a girl, living in a one-parent family, and more time spent playing on the computer were associated with heavy social media use on weekdays and weekends (all P < 0.05). Low socioeconomic position adolescents (low parental educational level and low household income) were more likely to show heavy social media use only on weekends (all P < 0.05). Children whose social media use was restricted by parents on weekdays or children whose social media use was supervised by parents on weekends had lower odds of heavy social media use (all P < 0.05). CONCLUSIONS: Being a girl, living in a one-parent family, or having a longer computer playing time were associated with heavy social media use on weekdays and weekends. More studies are needed to understand the factors associated with heavy social media use and the impact of heavy social media use on child health.

The chromosome-scale assembly of the Salvia rosmarinus genome provides insight into carnosic acid biosynthesis.

Rosemary (Salvia rosmarinus) is considered a sacred plant because of its special fragrance and is commonly used in cooking and traditional medicine. Here, we report a high-quality chromosome-level assembly of the S. rosmarinus genome of 1.11 Gb in size; the genome has a scaffold N50 value of 95.5 Mb and contains 40 701 protein-coding genes. In contrast to other diploid Labiataceae, an independent whole-genome duplication event occurred in S. rosmarinus at approximately 15 million years ago. Transcriptomic comparison of two S. rosmarinus cultivars with contrasting carnosic acid (CA) content revealed 842 genes significantly positively associated with CA biosynthesis in S. rosmarinus. Many of these genes have been reported to be involved in CA biosynthesis previously, such as genes involved in the mevalonate/methylerythritol phosphate pathways and CYP71-coding genes. Based on the genomes and these genes, we propose a model of CA biosynthesis in S. rosmarinus. Further, comparative genome analysis of the congeneric species revealed the species-specific evolution of CA biosynthesis genes. The genes encoding diterpene synthase and the cytochrome P450 (CYP450) family of CA synthesis-associated genes form a biosynthetic gene cluster (CPSs-KSLs-CYP76AHs) responsible for the synthesis of leaf and root diterpenoids, which are located on S. rosmarinus chromosomes 1 and 2, respectively. Such clustering is also observed in other sage (Salvia) plants, thus suggesting that genes involved in diterpenoid synthesis are conserved in the Labiataceae family. These findings provide new insights into the synthesis of aromatic terpenoids and their regulation.

SUMOylation facilitates the assembly of a Nuclear Factor-Y complex to enhance thermotolerance in Arabidopsis.

Heat stress (HS) has serious negative effects on plant development and has become a major threat to agriculture. A rapid transcriptional regulatory cascade has evolved in plants in response to HS. Nuclear Factor-Y (NF-Y) complexes are critical for this mechanism, but how NF-Y complexes are regulated remains unclear. In this study, we identified NF-YC10 (NF-Y subunit C10), a central regulator of the HS response in Arabidopsis thaliana, as a substrate of SUMOylation, an important post-translational modification. Biochemical analysis showed that the SUMO ligase SIZ1 (SAP AND MIZ1 DOMAIN-CONTAINING LIGASE1) interacts with NF-YC10 and enhances its SUMOylation during HS. The SUMOylation of NF-YC10 facilitates its interaction with and the nuclear translocation of NF-YB3, in which the SUMO interaction motif (SIM) is essential for its efficient association with NF-YC10. Further functional analysis indicated that the SUMOylation of NF-YC10 and the SIM of NF-YB3 are critical for HS-responsive gene expression and plant thermotolerance. These findings uncover a role for the SIZ1-mediated SUMOylation of NF-YC10 in NF-Y complex assembly under HS, providing new insights into the role of a post-translational modification in regulating transcription during abiotic stress responses in plants.

Lipopolysaccharide-binding protein as a biomarker in oral and maxillofacial tumors.

Oral and maxillofacial tumors (OMTs), such as oral squamous cell carcinoma (SCC), pleomorphic adenoma, and ameloblastoma, are common head and neck tumors. Lipopolysaccharide-binding protein (LBP) is a type I acute reactive protein, which participates in body inflammatory response modulation through lipopolysaccharide (LPS)-induced signaling pathway by targeting macrophages (expressing cluster of differentiation 204 [CD204]). Although it is well established that LBP is associated with the development of multiple types of cancer, little is known about the role of LBP in OMTs. This study aims to explore the expression of LBP in OMTs. Here, immunohistochemical (IHC) double staining of LBP and CD204 and enzyme-linked immunosorbent assay (ELISA) were conducted to explore the LBP expression in OMTs. The findings demonstrated that the LBP expression in OMTs was significantly elevated (p < 0.001). In addition, the LBP expression was associated with the clinical stage (p < 0.001), T classification (p < 0.001), and lymph node metastasis (p < 0.001, except ELISA) but independent of histological grade of SCC, gender, and age in patients with SCC. The optional cutoff of the LBP serum level is 0.721 µg/ml. To conclude, LBP contributes to the development of OMTs and could be a biomarker in the screening and predicting metastasis in patients with OMTs.

Factors associated with polypharmacy and the high risk of medication-related problems among older community-dwelling adults in European countries: a longitudinal study.

BACKGROUND: Polypharmacy can be defined as using five or more medications simultaneously. "Medication-related problems", an extension of polypharmacy, includes inappropriate prescribing, poor adherence, overdosage, underdosage, inappropriate drug selection, inadequate monitoring, adverse drug effects, and drug interactions. Polypharmacy and the high risk of medication-related problems among older people are associated with adverse health consequences due to drug-drug interactions, drug-disease interactions, and adverse drug effects. This study aims to assess the factors associated with polypharmacy and the high risk of medication-related problems among community-dwelling older people in the Netherlands, Greece, Croatia, Spain, United Kingdom. METHOD: This longitudinal study used baseline and follow-up data from 1791 participants of the Urban Health Center European project. Polypharmacy and the risk of medication-related problems were evaluated at baseline and follow-up using the Medication Risk Questionnaire. We studied factors in the domains (a) sociodemographic characteristics, (b) lifestyle and nutrition, and (c) health and health care use. Hierarchical logistic regression analyses were used to examine the factors associated with polypharmacy and the high risk of medication-related problems. RESULTS: Mean age was 79.6 years (SD ± 5.6 years); 60.8% were women; 45.2% had polypharmacy, and 41.8% had a high risk of medication-related problems. Women participants had lower odds of polypharmacy (OR = 0.55;95%CI:0.42-0.72) and a high risk of medication-related problems (OR = 0.50; 95%CI:0.39-0.65). Participants with a migration background (OR = 1.67;95%CI:1.08-2.59), overweight (OR = 1.37; 95%CI:1.04-1.79) and obesity (OR = 1.78;95%CI:1.26-2.51) compared to 'normal weight', with lower physical HRQoL (OR = 0.96, 95%CI:0.95-0.98), multi-morbidity (OR = 3.73, 95%CI:2.18-6.37), frailty (OR = 1.69, 95%CI:1.24-2.30), visited outpatient services (OR = 1.77, 95%CI: 1.09-2.88) had higher odds of polypharmacy. The associations with the high risk of medication-related problems were similar. CONCLUSIONS: Multiple factors in demography, lifestyle, nutrition, and health care use are associated with polypharmacy and the high risk of medication-related problems. Polypharmacy is a single element that may reflect the number of medications taken. The broader content of medication-related problems should be considered to assess the context of medication use among older people comprehensively. These provide starting points to improve interventions to reduce polypharmacy and high risk of medication-related problems. In the meantime, health professionals can apply these insights to identify subgroups of patients at a high risk of polypharmacy and medication-related problems. TRIAL REGISTRATION: The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.

Social Media Use and Health-Related Quality of Life Among Adolescents: Cross-sectional Study.

BACKGROUND: Using social media is a time-consuming activity of children and adolescents. Health authorities have warned that excessive use of social media can negatively affect adolescent social, physical, and psychological health. However, scientific findings regarding associations between time spent on social media and adolescent health-related quality of life (HRQoL) are not consistent. Adolescents typically use multiple social media platforms. Whether the use of multiple social media platforms impacts adolescent health is unclear. OBJECTIVE: The aim of this study was to examine the relationship between social media use, including the number of social media platforms used and time spent on social media, and adolescent HRQoL. METHODS: We analyzed the data of 3397 children (mean age 13.5, SD 0.4 years) from the Generation R Study, a population-based cohort study in the Netherlands. Children reported the number of social media platforms used and time spent on social media during weekdays and weekends separately. Children's HRQoL was self-reported with the EuroQol 5-dimension questionnaire-youth version. Data on social media use and HRQoL were collected from 2015 to 2019. Multiple logistic and linear regressions were applied. RESULTS: In this study, 72.6% (2466/3397) of the children used 3 or more social media platforms, and 37.7% (1234/3276) and 58.3% (1911/3277) of the children used social media at least 2 hours per day during weekdays and weekends, respectively. Children using more social media platforms (7 or more platforms) had a higher odds of reporting having some or a lot of problems on "having pain or discomfort" (OR 1.55, 95% CI 1.20 to 1.99) and "feeling worried, sad or unhappy" (OR 1.99, 95% CI 1.52 to 2.60) dimensions and reported lower self-rated health (ß -3.81, 95% CI -5.54 to -2.09) compared with children who used 0 to 2 social media platforms. Both on weekdays and weekends, children spent more time on social media were more likely to report having some or a lot of problems on "doing usual activities," "having pain or discomfort," "feeling worried, sad or unhappy," and report lower self-rated health (all P<.001). CONCLUSIONS: Our findings indicate that using more social media platforms and spending more time on social media were significantly related to lower HRQoL. We recommend future research to study the pathway between social media use and HRQoL among adolescents.

Evaluation design of the patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard (InAdvance): a randomised controlled trial.

BACKGROUND: Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The 'Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard' (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions. METHODS: In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs. DISCUSSION: The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care. TRIAL REGISTRATION: ISRCTN, ISRCTN24825698 . Registered 17/12/2020.