Association between life-course cigarette smoking and metabolic syndrome: a discovery-replication strategy

Background The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples. Methods Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS. Results In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged < 70 years (Pinteraction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04–1.63). The interaction of smoking with age was also replicated. Conclusions Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged < 70 years.

Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX

Tpp49Aa1 from Lysinibacillus sphaericus is a Toxin_10 family protein that must interact with Cry48Aa1, a 3-domain crystal protein, to produce potent mosquitocidal activity, specifically against Culex quinquefasciatus mosquitoes. We use Culex cell lines to demonstrate for the first time transient detrimental effects of individual toxin components and widen the known target range of the proteins. MHz serial femtosecond crystallography at a nano-focused X-ray free electron laser allowed rapid and high-quality data collection to determine the Tpp49Aa1 structure at 2.2 Å resolution from the merged X-ray diffraction data. The structure revealed the packing of Cry49Aa1 within the natural nanocrystals isolated from sporulated bacteria, as a homodimer with a large intermolecular interface. We then modelled the potential interaction between Tpp49Aa1 and Cry48Aa1. The structure sheds light on natural crystallisation and, along with cell-based assays broadens our understanding of this two-component system.

A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

The Interaction Between Pulmonary Fibrosis and COVID-19 and the Application of Related Anti-Fibrotic Drugs

COVID-19 is a highly contagious respiratory disease, which mainly affects the lungs. Critically ill patients are easily complicated by cytokine storms, acute respiratory distress syndrome (ARDS), and respiratory failure, which seriously threaten their lives. Pulmonary fibrosis (PF) is a common interstitial lung disease, and its pathogenesis may involve the participation of a variety of immune cells and inflammatory factors. Current studies have shown that patients with COVID-19 may be complicated by pulmonary fibrosis, and patients with pulmonary fibrosis may also be at higher risk of contracting COVID-19 than healthy people. Pulmonary fibrosis is an important risk factor leading to the aggravation of COVID-19 disease. COVID-19 complicated by cytokine storm and ARDS mechanism pathways are similar to the pathogenesis of pulmonary fibrosis. The potential interaction between pulmonary fibrosis and COVID-19 can cause acute exacerbation of the patient’s condition, but the potential mechanism between the two has not been fully elucidated. Most of the drug treatment programs for COVID-19-related pulmonary fibrosis are currently formulated about the relevant guidelines for idiopathic pulmonary fibrosis (IPF), and there is no clear drug treatment program recommendation. This article aims to summarize the relevant mechanism pathways of COVID-19 and pulmonary fibrosis, explore the interrelationships and possible mechanisms, and discuss the value and risks of existing and potential COVID-19-related pulmonary fibrosis treatment drugs, to provide reference for anti-fibrosis treatment for patients.

Physical-chemical and Biological Properties of Novel Resin-based Composites for Dental Applications

Insufficient mechanical properties of hydroxyapatite -based composites prompted the search for new and effective solutions for dental applications. To improve the mechanical properties without losing the remineralization potential, the use of hybrid fillers was proposed. The first of them was based on the formation of hydroxyapatite (HA) layer on the surface of SYLOID®244 silica. The second of the investigated fillers was created by simultaneous synthesis of nanoparticles from precursors of HA and silica. The obtained fillers were extensively characterized by spectral methods including X-ray Diffractometry (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), and X-ray fluorescence (XRF), as well as by Scanning Electron Microscopy (SEM)/Energy Dispersive Spectroscopy (EDS). Tests using probiotic microorganisms were an important part of the analysis, indicating that there was no potential interaction of the materials with microflora. The tests of degree of conversion, depth of cure, opacity, sorption, solubility, flexural and compressive strength, and the remineralizing potential also showed that the composites with nano-sized silica/HA showed better mechanical properties than the composites with HA alone or commercial silica and at the same time the remineralization remained at the desired level. Thus, the proposed composite has a high application potential in the creation of implants and dental materials.

Understanding the social impacts of enforcement activities on illegal wildlife trade in China

Illegal wildlife trade enforcement is a cornerstone conservation strategy worldwide, yet we have a limited understanding on its social impacts. Using Chinese online wildlife seizure news (2003–2018), we evaluated the interactions among enforcement operations, news frequency, and social engagement (i.e., whistle-blowing) frequency. Our results showed that intensive enforcement operations, which commenced after 2012, have social impacts by increasing the frequency of all seizure news significantly by 28% [95% Confidence Interval (CI): 5%, 51%] and those via whistle-blowing by 24% [95% CI: 2%, 45%], when compared to counterfactual models where possible confounding factors were accounted for. Furthermore, we revealed the potential interaction between enforcement seizure news with and without social engagement, and the consequential social feedback process. Of the species identified from ‘whistle-blowing’ news, up to 28% are considered as high conservation priorities. Overall, we expanded our understanding of the enforcement impacts to social dimensions, which could contribute to improving the cost-effectiveness of such conservation efforts.

Does healthy lifestyle attenuate the detrimental effects of urinary polycyclic aromatic hydrocarbons on phenotypic aging? An analysis from NHANES 2001–2010

Objectives: It remains unknown whether healthy lifestyle attenuates the detrimental effects of urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) on aging. This study aims: 1) to examine the associations of OH-PAHs and lifestyle with Phenotypic Age Acceleration (PhenoAge.Accel), a novel aging measure, respectively; and 2) to evaluate the potential interaction effects of OH-PAHs and lifestyle on PhenoAge.Accel. Methods: Cross-sectional data of 2579 participants (aged 20-84 years, n=1292 females) from the National Health and Nutrition Examination Survey for years 2001-2010 were analyzed. A lifestyle index was constructed based on five components (drinking, smoking, body mass index, physical activity, and diet), ranging from 0 to 5. We calculated PhenoAge.Accel using algorithms developed previously. General linear regression models were used to examine the associations. Results: We observed strong associations of OH-PAHs and lifestyle with PhenoAge.Accel. For instance, one unit increase in ∑NAP (sum of 1- and 2-hydroxynaphthalene) was associated with 0.37 year (95% confidence interval [CI]: 0.26, 0.48) increase in PhenoAge.Accel. We did not observe statistically significant interaction effects between OH-PAHs and lifestyle on PhenoAge.Accel. After stratified by sex, we observed strong associations as well as statistically significant interactions of OH-PAHs and lifestyle with PhenoAge.Accel among females. Conclusions: Both OH-PAHs and lifestyle were independently associated with phenotypic aging and there were statistically significant interactions between OH-PAHs and lifestyle on phenotypic aging among females. The findings highlight the importance of adherence to a healthy lifestyle to attenuate the detrimental effects of exposures to PAHs on phenotypic aging among females.

Undermining the gendered genre: Kabuki in manga

According to Jaqueline Berndt, Thomas LaMarre, and other critics, manga is a highly participatory media form. Narratives with vibrant characters and creative inconsistences in the plotline encourage the reader to recontextualise the text, create new contents and unfold activities which go beyond reading (such as fan art and CosPlay). Recent popularity of manga about Japanese traditional arts – for example, Kabuki – further expanded the potential interaction with manga and other popular media to include (re)discovering traditional Japanese culture. Examples, such as Kabukumon by Tanaka Akio and David Miyahara (Morning 2008-2011), or Kunisaki Izumo no jijō by Hirakawa Aya (Weekly Shōnen Sunday 2010-2014) and a variety of other manga, anime and light novels exemplify this tendency. Consequently, influential franchises, such as Naruto and One Piece boast adaptations as Super Kabuki stage-plays. Furthermore, Jessica Bauwens-Sugimoto observes how thematic and stylistic overreaching in contemporary manga further distort the notions of the gendered genre that lays at the foundation of the manga industry. In this case, Kabuki theatre as a theme employs a variety of gender fluid characters and situations. For this purpose, Kabuki manga utilise cross-genre narrative and stylistic tropes, from overtly parodying borrowed tropes, to homage, and covert inclusions. On the example of Kabuki-manga I will explore a larger trend in manga to employ elements of female genres in male narratives, thus expanding the target readership. My paper explores specific mechanism that facilitates reading manga cross-genre, I also inquire what novel critical potential thematic and stylistic exchange between audiences may entail.

Involvement of P-gp on Reversing Multidrug Resistance Effects of 23-Hydroxybetulinic Acid on Chemotherapeutic Agents

Betulinic acid (BA) and 23-Hydroxybetulinic acid (23-HBA) are natural products with similar structures, which show a range of biological effects including cytotoxicity activity. The aim of current research was to investigate and evaluate the combinational cytotoxicity of BA and 23-HBA with chemotherapeutic agents in vitro, and to clarify the potential interaction and related mechanism with P-gp. Instead of BA, 23-HBA could increase cytotoxicity of MCF-7/ADR cells to adriamaycin (ADR) and vincristine (VCR). The intracellular accumulation of ADR/VCR in MCF-7/ADR cells was obviously increased in the presence of 23-HBA. Furthermore, 23-HBA could show dose-dependent increase on the transport of VCR and digoxin, which are typical P-gp substrates, in both MDCK-MDR1 and Caco-2 cells. However, the transport of BA and 23-HBA was not influenced by P-gp inhibition in MDCK-MDR1 cells. MDR1 shift assay and molecular docking model suggested that both compounds showed interaction with P-gp, yet the binding affinity and sites are different. In conclusion, 23-HBA could strongly improve the efficacy of anti-tumor agents in multidrug resistance (MDR) cells, which was related to P-gp inhibition. The MDR1 shift assay and molecular docking study further revealed that 23-HBA and BA showed different interaction modes with P-gp.

Socialising Church Space

<p>For hundreds of years the Christian Church stood as the pillar of occidental cities, structuring society and the urban fabric. At the time of European colonisation, the impact of the Church on New Zealand society was less significant than it had been centuries before. Social priorities were slowly shifting away from religious fanaticism, as such; the church did not influence the urban environment to the same level. Church buildings became increasingly isolated from their urban setting, with less impact on their surrounding environment. In addition, New Zealand urban development was expanding, creating the need for vehicular transport. For the majority of Christians, driving to church continues to be commonplace. What little exterior space churches have is typically used as car parking. This space surrounding many church buildings is functional and utilitarian, resulting in an uninviting exterior with no pedestrian interactivity. This has limited the potential interaction between the church and local community. To fully understand the New Zealand model, ten churches were identified and analysed in Wellington. Information and evidence were gathered on how to address the lack of inviting exterior church space. A comparative analysis model was used to identify sites with particular potential for improved design. Engagement with the respective church communities was then necessary to establish a deeper understanding of each site and the needs of the community. Comparative analysis and community engagement methods produced a set of criteria for designing in each space. By following the same process for each church space, the resulting designs propose spaces which allow opportunities for both members of the church and the general public to interact. Designs specifically focus on creating vibrant spaces with less emphasis on the architectural qualities and utilitarian programmes of church space. They are also multipurpose and flexible, taking into account weekly engagement and potential future development.</p>