bluuebunny/crossref_metadata_2025 huggingface dataset:
Air Quality Dispersion Modelling to Evaluate CIPP Installation Styrene Emissions
Authors: Matthews Elizabeth , Kraft John , Hossain Gazi , Bednar Anthony , Laber Charles , Alam Shaurav , Manzur Tanvir , Matthews John , Howell Jason , Eklund Sven
Published: October 2022

Cured-in-place pipe (CIPP) is one of the most popular in situ rehabilitation techniques to repair sewer and water pipes. While there are multiple approaches to curing CIPP, steam-curing of styrene-based resins has been found to be associated with air-borne chemical emissions. Health officials, utilities and industry representatives have recognized the need to know more about these emissions, especially styrene. Such concern has led to multiple studies investigating the concentrations of volatile organic compounds on CIPP installation sites. This study expands upon previous effort by modeling worst-case, steam-cured CIPP emissions over a 5-year weather record. The effort also includes calibration of the model to emissions averages over the work day rather than instantaneous field measurements. Dispersion modelling software, AERMOD, was utilized to model the styrene component of CIPP emissions on two CIPP installation sites in the US. Based on the analysis results, it was found that the styrene emitted from stacks dissipates rapidly with styrene concentrations only exceeding minimum health and safety threshold levels at distances close to the stack (2 m or less). The values predicted by the model analysis are comparable with the field measured styrene concentrations from other studies. Current safety guidelines in the US recommend a 4.6-m (15-ft) safety perimeter for stack emission points. The results of this study indicate that significant and lasting health impacts are unlikely outside recommended safety perimeter. The results also validate the importance of enforcing recommended safety guidance on steam-cured CIPP sites.
Development and Validation of a Set of Instruments to Measure Food Environments
Authors: Araneda-Flores Jacqueline , Moresco Patricio Oliva , Quezada-Figueroa Gladys , Lobos-Fernandez Luz , Leyton Barbara , Pinheiro Anna Christina
Published: October 2022

Background: There is worldwide interest in measuring local food environments (FEs). The aim of this study was to develop and validate a set of instruments to evaluate FEs in Chile. Methods: Based on the development and validation of four instruments to measure FEs, a literature review, an evaluation by experts, and the implementation of a pilot tool in the FEs of schoolchildren from nine public schools in the commune of Chillán, Chile, were used. Results: A tool to evaluate FEs was provided, based on three dimensions: availability, variety, and advertising of healthy foods. A total of 1928 foods points of purchase were evaluated. The reliability was evaluated by Cronbach’s alpha. Some 74% of the foods’ points of purchase were store locations. The reliability of the four instruments was high to acceptable (store: 0.90; institution: 0.77; street food: 0.74; restaurant: 0.68). Unhealthy foods were highlighted by the scores obtained: store (6.08 ± 4.07; range: 0–13), restaurant (3.95 ± 1.75; range: 0–10), street food (1.18 ± 1.56; range: 0–7), and institution FEs (3.38 ± 2.78; range: 0–9). Conclusions: The results of this tool can provide information to governments for incorporating structural measures to ensure adequate availability, variety, and advertising of healthy foods in different FEs.
Fundamental Aspects of the Development of a Model of an Integrated Health Care System for the Prevention of Iron Deficiency Anemia among Adolescent Girls: A Qualitative Study
Authors: Sari Puspa , Herawati Dewi Marhaeni Diah , Dhamayanti Meita , Hilmanto Dany
Published: October 2022

Iron deficiency anemia (IDA) in adolescent girls is a problem that has not been resolved. This study aimed to explore the critical aspects of an integrated health care system model for preventing IDA in adolescent girls in a rural area of Indonesia. This qualitative research employed a grounded theory approach in order to build a substantive theory. This study used in-depth interviews with adolescents, parents, teachers, health workers, and persons in charge of adolescent programs at the health office, education office, and ministry of religion. Purposive sampling was performed until data saturation was achieved. Codes, categories, and themes were generated through thematic data analysis to develop a substantive theory. Data analysis was performed using MAXQDA 2022 software. A total of 41 people participated in this study. This investigation generated twenty-two categories and seven themes. These themes relate to policymaker commitments, stakeholder governance, quality, adolescents’ lifestyles, adolescents’ self-factors, adolescents’ access to health services, and social support. The themes identified become fundamental aspects of the integrated health care system model for preventing IDA in adolescent girls. The model of the integrated health care system consists of several essential points, which include awareness and efforts from policymakers and adolescent girls, supported by parents, teachers, and the community.
What Drives the Influence of Health Science Communication Accounts on TikTok? A Fuzzy-Set Qualitative Comparative Analysis
Authors: Liu Ran , Yang Tianan , Deng Wenhao , Liu Xiaoyan , Deng Jianwei
Published: October 2022

Medical institutions face a variety of challenges as they seek to enhance their reputation and increase the influence of their social media accounts. Becoming a social media influencer in the health field in today’s complex online environment requires integrated social and technical systems. However, rather than holistically investigating the mechanism of account influence, studies have focused on a narrow subset of social and technical conditions that drive online influence. We attribute this to the mismatch between complex causality problems and traditional symmetric regression methods. In this study, we adopted an asymmetric configurational perspective that allowed us to test a causally complex model of the conditions that create strong and not-strong account influence. We used fuzzy-set qualitative comparative analysis (fsQCA) to detect the effects of varying configurations of three social system characteristics (i.e., an oncology-related attribute, a public attribute, and comment interaction) and two technical system characteristics (i.e., telepresence and video collection) on the TikTok accounts of 63 elderly Chinese doctors (60 to 92 years old). Our results revealed two pathways associated with distinct sociotechnical configurations to strong account influence and three pathways associated with distinct sociotechnical configurations to not-strong account influence. Furthermore, the results confirmed that a single antecedent condition cannot, on its own, produce an outcome, i.e., account influence. Multiple inter-related conditions are required to produce an influential account. These results offer a more holistic picture of how health science communication accounts operate and reconcile the scattered results in the literature. We also demonstrate how configurational theory and methods can be used to analyze the complexities of social media platforms.
Analysis and Measurement of Barriers to Green Transformation Behavior of Resource Industries
Authors: Li Cunfang , Song Tao , Wang Wenfu , Gu Xinyi , Li Zhan , Lai Yongzeng
Published: October 2022

To effectively guide and stimulate the green transformation behavior of resource industries and promote the sustainable and high-quality development of the region, it is necessary to deeply analyze and clarify the barrier factors of the green transformation behavior of resource industries. This study measures the green transformation efficiency of the resource industries by selecting the panel data of the mining industry from 29 Chinese provinces, based on the DEA-SBM model, and employing the ideas and methods of system engineering, for the years 2012–2019. Hence, the study employs the Tobit model to verify the factors that hinder the green transformation behavior of the resource industries. The results show that the (1) resource industries’ barriers against the green transformation behavior form a significant barrier effect by inhibiting the efficiency of green transformation; (2) there is a difference in the intensity of the effect of the resource industries’ barriers to the green transformation behavior; (3) regional heterogeneity exists in the effects of the barriers to the green transformation behavior of the resource industries. The findings of the study can provide a scientific basis for further improving the effectiveness of policies related to the green transformation behavior of resource industries.
Effectiveness and Cost-Effectiveness of Case Management in Advanced Heart Failure Patients Attended in Primary Care: A Systematic Review and Meta-Analysis
Authors: Checa Caterina , Canelo-Aybar Carlos , Suclupe Stefanie , Ginesta-López David , Berenguera Anna , Castells Xavier , Brotons Carlos , Posso Margarita
Published: October 2022

Aims: Nurse-led case management (CM) may improve quality of life (QoL) for advanced heart failure (HF) patients. No systematic review (SR), however, has summarized its effectiveness/cost-effectiveness. We aimed to evaluate the effect of such programs in primary care settings in advanced HF patients. We examined and summarized evidence on QoL, mortality, hospitalization, self-care, and cost-effectiveness. Methods and results: The MEDLINE, CINAHL, Embase, Clinical Trials, WHO, Registry of International Clinical Trials, and Central Cochrane were searched up to March 2022. The Consensus Health Economic Criteria instrument to assess risk-of-bias in economic evaluations, Cochrane risk-of-bias 2 for clinical trials, and an adaptation of Robins-I for quasi-experimental and cohort studies were employed. Results from nurse-led CM programs did not reduce mortality (RR 0.78, 95% CI 0.53 to 1.15; participants = 1345; studies = 6; I2 = 47%). They decreased HF hospitalizations (HR 0.79, 95% CI 0.68 to 0.91; participants = 1989; studies = 8; I2 = 0%) and all-cause ones (HR 0.73, 95% CI 0.60 to 0.89; participants = 1012; studies = 5; I2 = 36%). QoL improved in medium-term follow-up (SMD 0.18, 95% CI 0.05 to 0.32; participants = 1228; studies = 8; I2 = 28%), and self-care was not statistically significant improved (SMD 0.66, 95% CI −0.84 to 2.17; participants = 450; studies = 3; I2 = 97%). A wide variety of costs ranging from USD 4975 to EUR 27,538 was observed. The intervention was cost-effective at ≤EUR 60,000/QALY. Conclusions: Nurse-led CM reduces all-cause hospital admissions and HF hospitalizations but not all-cause mortality. QoL improved at medium-term follow-up. Such programs could be cost-effective in high-income countries.
Possible Association between Physical and Cognitive Function and Stumbling and Falling in Elderly Workers
Authors: Morita Kotaro , Nogawa Kazuhiro , Watanabe Yuuka , Sakuma Sayaka , Sakata Koichi , Ito Katsuyuki , Kumeda Chika , Suwazono Yasushi
Published: October 2022

The aim of this paper is to examine the association between physical and cognitive function and stumbling and falling in elderly workers by conducting work-related questionnaire surveys and physical and cognitive function measurements. A total of 611 men and 121 women aged 40–69 years who participated in physical function measurements between June 2017 and June 2021 were included in the study. The general physical function measurements of upper and lower limb muscle strength, dynamic and static balance, and agility and cognitive function included grip strength, Repeated Rise Test, Trail Making test (TMT), and Three-Meter Time Up Go Test (TUG). We also asked the men and women about their experience of falling and stumbling. Logistic regression analysis showed significant odds ratios (OR) for the associations between stumbling in men and age (OR: 1.98), mental burden (OR: 2.44), frequency of field work (OR: 1.74), seated stepping test count (OR: 0.95), and TMTB time (OR: 0.99). Significant ORs were found between falling in men and age (OR: 2.55), mental burden (OR: 2.40), exercise habits (OR: 2.55), and smoking (OR: 2.00). Significant ORs were found between stumbling in women and d_TUG (OR: 1.59) and mental burden (OR: 6.42). The study suggests that there may be an association between cognitive and physical decline and stumbling and falling in elderly workers.
Physical Impact of a Typical Training Session with Different Volumes on the Day Preceding a Match in Academy Soccer Players
Authors: Douchet Tom , Paizis Christos , Babault Nicolas
Published: October 2022

French academies almost all implement reactivity drills and small-sided games (SSG) the day preceding a match (MD-1). The present study aimed to determine the physical impact of different training durations on MD-1 on the subsequent matchday performance (MD). Eleven elite U19 academy soccer players conducted three typical training sessions lasting 45 min (TS45), 60 min (TS60) and 75 min (TS75) on MD-1. During TS60, warm-up, reactivity and SSG were 10, 15 and 24 min, respectively, plus coaches’ feedback or water breaks. Durations of all training components decreased by 25% for TS45 and increased by 25% for TS75. Tests were conducted on MD-4 (CONTROL) and MD before the match (TEST). Tests consisted of a counter movement jump (CMJ), 20 m sprint, Illinois agility test (IAT) and Hooper questionnaire. CONTROL values were similar over the three experimental conditions. TEST on MD revealed greater CMJ for TS45 (42.7 ± 5.1 cm) compared to TS60 (40.5 ± 5.5 cm, p = 0.032) and TS75 (40.9 ± 5.7 cm, p = 0.037). 20 m time was lower for TS45 (3.07 ± 0.10 s, p < 0.001) and TS60 (3.13 ± 0.10 s, p = 0.017) compared to TS75 (3.20 ± 0.10 s). IAT time was lower on TS45 (14.82 ± 0.49 s) compared to TS60 (15.43 ± 0.29 s, p < 0.001) and TS75 (15.24 ± 0.33 s, p = 0.006). Furthermore, the Hooper index was lower at TEST for TS45 (7.64 ± 1.50) compared to TS60 (11.00 ± 3.49, p = 0.016) and TS75 (9.73 ± 2.41, p = 0.016), indicating a better readiness level. We concluded that, as training session duration increases, performance decreases on MD. A 45 min training session including reactivity and SSG exercises is therefore recommended on MD-1.
Immobilization of Biomass Materials for Removal of Refractory Organic Pollutants from Wastewater
Authors: Liu Danxia , Yang Xiaolong , Zhang Lin , Tang Yiyan , He Huijun , Liang Meina , Tu Zhihong , Zhu Hongxiang
Published: October 2022

In the field of environmental science and engineering, microorganisms, enzymes and algae are promising biomass materials that can effectively degrade pollutants. However, problems such as poor environmental adaptability, recycling difficulties, and secondary pollution exist in the practical application of non-immobilized biomass materials. Biomass immobilization is a novel environmental remediation technology that can effectively solve these problems. Compared with non-immobilized biomass, immobilized biomass materials have the advantages of reusability and stability in terms of pH, temperature, handling, and storage. Many researchers have studied immobilization technology (i.e., methods, carriers, and biomass types) and its applications for removing refractory organic pollutants. Based on this, this paper reviews biomass immobilization technology, outlines the mechanisms and factors affecting the removal of refractory organic pollutants, and introduces the application of immobilized biomass materials as fillers for reactors in water purification. This review provides some practical references for the preparation and application of immobilized biomass materials and promotes further research and development to expand the application range of this material for water purification.
Analysis of the Operational Efficiency of Basic Medical Insurance for Urban and Rural Residents: Based on a Three-Stage DEA Model
Authors: Liu Tong , Gao Yufei , Li Hui , Zhang Liping , Sun Jiangjie
Published: October 2022

Following the integration of the urban residents’ medical insurance into the new rural cooperative medical insurance in 2016, China has now formed a basic medical insurance system with the urban workers’ basic medical insurance system and the rural residents’ basic medical insurance system as the main entities. With the development of basic medical insurance, the protection for residents is becoming more and more comprehensive, and its fund expenditure also increases, so it is necessary to research the efficiency of the medical insurance fund expenditure. This paper conducts a three-stage DEA analysis of the efficiency of basic health insurance for urban and rural residents in 31 provinces, based on a Chinese panel data from 2017 to 2020. It is found that China’s health insurance operation is still in the development stage, with four regions in the efficiency frontier and Guizhou province having the lowest efficiency value nationwide. The GDP and fiscal investment on social security effectively reduce the input redundancy in the basic health insurance operation, which contributes to the efficiency of the health insurance operation. This study further proposes suggestions and countermeasures to improve the operational efficiency of China’s basic health insurance, based on the empirical results: (1) develop the economy and broaden the financing sources; (2) improve the level of health care services and improve the efficiency driven by quality; and (3) improve the level of health insurance supervision through multiple measures.
Controlled Trial Examining the Strength-Based Grit Wellbeing and Self-Regulation Program for Young People in Residential Settings for Substance Use
Authors: Quinn Catherine A. , Walter Zoe C. , de Andrade Dominique , Dingle Genevieve , Haslam Catherine , Hides Leanne
Published: October 2022

This cohort-controlled trial examined whether the 12-session Grit Wellbeing and Self-regulation Program enhanced the treatment outcomes of young people accessing residential alcohol and other drug (AOD) treatment. Grit focuses on increasing wellbeing and reducing substance use and mental health problems by building self-regulation skills, strengths, social connections, and health behaviours. Participants were 194 (66% male, Mage 27.40) young people (aged 18–35 years) accessing a six-week residential treatment program for substance use. Participants received standard treatment, or standard treatment plus Grit (two sessions/week for six weeks). The primary outcome was substance use, measured as: (i) global substance use and (ii) alcohol, methamphetamine, and cannabis use involvement. Secondary outcomes included wellbeing, depression, anxiety, and vocational engagement. Participants were assessed at baseline, and 6-weeks (secondary outcomes only), 3-months, 6-months, and 12-months post-program enrolment. Results revealed that both groups showed a significant improvement in all outcomes at three months, and improvements were maintained at 6- and 12-month follow-ups. The Grit group had a larger reduction in methamphetamine and cannabis use involvement compared to the control group. This study presents promising evidence that a six-week residential program can achieve improvements in AOD use, depression, anxiety, wellbeing and vocational engagement. Further, targeting self-regulation may enhance such programs.
Physical Activity, Empowerment of the Immune System and Public Health: What We Learned from the COVID-19 Pandemic
Authors: Pitanga Francisco José Gondim
Published: October 2022

The importance of physical activity for the cardiovascular, metabolic and mental health systems with its repercussions for public health has been studied for some time, although further studies are needed due to the depletion of health services observed during the COVID-19 pandemic [...]
Transcriptomic and Physiological Analyses Reveal Potential Genes Involved in Photoperiod-Regulated β-Carotene Accumulation Mechanisms in the Endocarp of Cucumber (Cucumis sativus L.) Fruit
Authors: Obel Hesbon Ochieng , Cheng Chunyan , Tian Zhen , Njogu Martin Kagiki , Li Ji , Du Shengli , Lou Qunfeng , Zhou Junguo , Yu Xiaqing , Ogweno Joshua Otieno , Chen Jinfeng
Published: October 2022

The accumulation of carotenoids in plants is a key nutritional quality in many horticultural crops. Although the structural genes encoding the biosynthetic enzymes are well-characterized, little is known regarding photoperiod-mediated carotenoid accumulation in the fruits of some horticultural crops. Herein, we performed physiological and transcriptomic analyses using two cucumber genotypes, SWCC8 (XIS-orange-fleshed and photoperiod-sensitive) and CC3 (white-fleshed and photoperiod-non-sensitive), established under two photoperiod conditions (8L/16D vs. 12L/12D) at four fruit developmental stages. Day-neutral treatments significantly increased fruit β-carotene content by 42.1% compared to short day (SD) treatments in SWCC8 at 40 DAP with no significant changes in CC3. Day-neutral condition elevated sugar levels of fruits compared to short-day treatments. According to GO and KEGG analyses, the predominantly expressed genes were related to photosynthesis, carotenoid biosynthesis, plant hormone signaling, circadian rhythms, and carbohydrates. Consistent with β-carotene accumulation in SWCC8, the day-neutral condition elevated the expression of key carotenoid biosynthesis genes such as PSY1, PDS, ZDS1, LYCB, and CHYB1 during later stages between 30 to 40 days of fruit development. Compared to SWCC8, CC3 showed an expression of DEGs related to carotenoid cleavage and oxidative stresses, signifying reduced β-carotene levels in CC3 cucumber. Further, a WGCNA analysis revealed co-expression between carbohydrate-related genes (pentose-phosphatase synthase, β-glucosidase, and trehalose-6-phosphatase), photoperiod-signaling genes (LHY, APRR7/5, FKF1, PIF3, COP1, GIGANTEA, and CK2) and carotenoid-biosynthetic genes, thus suggesting that a cross-talk mechanism between carbohydrates and light-related genes induces β-carotene accumulation. The results highlighted herein provide a framework for future gene functional analyses and molecular breeding towards enhanced carotenoid accumulation in edible plant organs.
Spark Plasma Sintering-Assisted Synthesis of Bi2Fe4O9/Bi25FeO40 Heterostructures with Enhanced Photocatalytic Activity for Removal of Antibiotics
Authors: Liu Zhifei , Tan Yaqi , Ruan Xuefeng , Guo Jing , Li Wei , Li Jiajun , Ma Hongyu , Xiong Rui , Wei Jianhong
Published: October 2022

Bismuth ferrite-based heterojunction composites have been considered as promising visible-light responsive photocatalysts because of their narrow band gap structure; however, the synthetic methods reported in the literature were usually time-consuming. In this study, we report a facile and quick preparation of bismuth ferrite-based composites by the hydrothermal method, combined with spark plasma sintering (SPS), a technique that is usually used for the high-speed consolidation of powders. The result demonstrated that the SPS-assisted synthesized samples possess significant enhanced photoelectric and photocatalytic performance. Specifically, the SPS650 (sintered at the 650 °C for 5 min by SPS) exhibits a 1.5 times enhancement in the photocurrent density and a 3.8 times enhancement in the tetracycline hydrochloride photodegradation activity than the unmodified bismuth ferrite samples. The possible influence factors of SPS on photoelectric and photocatalytic performance of bismuth ferrite-based composites were discussed carefully. This study provides a feasible method for the facile and quick synthesis of a highly active bismuth ferrite-based visible-light-driven photocatalyst for practical applications.
SAXS Examinations of the Redox-Dependent Formation of a DNA-SOD1 Complex
Authors: Wang Huiling , Wang Mingfang , Nie Zefeng , Qiu Shuang , Huang Xiaoping , Li Xiang , Cui Yanfang , Liu Chunrong , Liu Changlin
Published: October 2022

Cu/Zn superoxide dismutase (SOD1) plays a key role in the maintenance of cellular reactive oxygen species (ROS) homeostasis as an antioxidant enzyme. We recently found that SOD1 is involved in the regulation of gene expression in response to changes in cellular ROS levels by binding to DNA-specific sequences. Moreover, the SOD1 binding to DNA was observed to be redox-dependent in solutions. Thus, we examined the redox-dependent DNA binding of SOD1 by multiple measurements, including small-angle X-ray scattering (SAXS), indicating the redox-dependent formation of a DNA-SOD1 complex in solutions. The redox-dependent formation of the DNA-SOD1 complex could underlie the SOD1 regulation of gene expression.
Internalized Amyloid-β (1-42) Peptide Inhibits the Store-Operated Calcium Entry in HT-22 Cells
Authors: Poejo Joana , Orantos-Aguilera Yolanda , Martin-Romero Francisco Javier , Mata Ana Maria , Gutierrez-Merino Carlos
Published: October 2022

Dysregulation in calcium signaling pathways plays a major role in the initiation of Alzheimer’s disease (AD) pathogenesis. Accumulative experimental evidence obtained with cellular and animal models, as well as with AD brain samples, points out the high cytotoxicity of soluble small oligomeric forms of amyloid-β peptides (Aβ) in AD. In recent works, we have proposed that Aβ-calmodulin (CaM) complexation may play a major role in neuronal Ca2+ signaling, mediated by CaM-binding proteins (CaMBPs). STIM1, a recognized CaMBP, plays a key role in store-operated calcium entry (SOCE), and it has been shown that the SOCE function is diminished in AD, resulting in the instability of dendric spines and enhanced amyloidogenesis. In this work, we show that 2 and 5 h of incubation with 2 μM Aβ(1-42) oligomers of the immortalized mouse hippocampal cell line HT-22 leads to the internalization of 62 ± 11 nM and 135 ± 15 nM of Aβ(1-42), respectively. Internalized Aβ(1-42) oligomers colocalize with the endoplasmic reticulum (ER) and co-immunoprecipitated with STIM1, unveiling that this protein is a novel target of Aβ. Fluorescence resonance energy transfer measurements between STIM1 tagged with a green fluorescent protein (GFP) and Aβ(1-42)-HiLyte™-Fluor555 show that STIM1 can bind nanomolar concentrations of Aβ(1-42) oligomers at a site located close to the CaM-binding site in STIM1. Internalized Aβ(1-42) produced dysregulation of the SOCE in the HT-22 cells before a sustained alteration of cytosolic Ca2+ homeostasis can be detected, and is elicited by only 2 h of incubation with 2 μM Aβ(1-42) oligomers. We conclude that Aβ(1-42)-induced SOCE dysregulation in HT-22 cells is caused by the inhibitory modulation of STIM1, and the partial activation of ER Ca2+-leak channels.
Zn-Catalyzed Regioselective and Chemoselective Reduction of Aldehydes, Ketones and Imines
Authors: Zhang Miaomiao , Jiao Hongmei , Ma Haojie , Li Ran , Han Bo , Zhang Yuqi , Wang Jijiang
Published: October 2022

An operationally convenient Zn-catalyzed synthesis of alcohols by the reduction of aldehydes, ketones, and α,β-unsaturated aldehydes/ketones is reported. It is a rare example of using mild and sustainable HBpin as a reductant for catalytic reduction of carbonyl compounds in the absence of acid or base as hydrolysis reagent. The reaction is upscalable and proceeds in high selectivity without the formation of boronate ester by-products, and tolerates sensitive functionalities, such as iodo, bromo, chloro, fluoro, nitro, trifluoromethyl, aminomethyl, alkynyl, and amide. The Zn(OAc)2/HBpin combination has been also proved to be chemoselective for the C=N reduction of imine analogs.
Role of Glycolysis and Fatty Acid Synthesis in the Activation and T Cell-Modulating Potential of Dendritic Cells Stimulated with a TLR5-Ligand Allergen Fusion Protein
Authors: Goretzki Alexandra , Lin Yen-Ju , Zimmermann Jennifer , Rainer Hannah , Junker Ann-Christine , Wolfheimer Sonja , Vieths Stefan , Scheurer Stephan , Schülke Stefan
Published: October 2022

Trained immune responses, based on metabolic and epigenetic changes in innate immune cells, are de facto innate immune memory and, therefore, are of great interest in vaccine development. In previous studies, the recombinant fusion protein rFlaA:Betv1, combining the adjuvant and toll-like receptor (TLR)5-ligand flagellin (FlaA) and the major birch pollen allergen Bet v 1 into a single molecule, significantly suppressed allergic sensitization in vivo while also changing the metabolism of myeloid dendritic cells (mDCs). Within this study, the immune–metabolic effects of rFlaA:Betv1 during mDC activation were elucidated. In line with results for other well-characterized TLR-ligands, rFlaA:Betv1 increased glycolysis while suppressing oxidative phosphorylation to different extents, making rFlaA:Betv1 a suitable model to study the immune–metabolic effects of TLR-adjuvanted vaccines. In vitro pretreatment of mDCs with cerulenin (inhibitor of fatty acid biosynthesis) led to a decrease in both rFlaA:Betv1-induced anti-inflammatory cytokine Interleukin (IL) 10 and T helper cell type (TH) 1-related cytokine IL-12p70, while the pro-inflammatory cytokine IL 1β was unaffected. Interestingly, pretreatment with the glutaminase inhibitor BPTES resulted in an increase in IL-1β, but decreased IL-12p70 secretion while leaving IL-10 unchanged. Inhibition of the glycolytic enzyme hexokinase-2 by 2-deoxyglucose led to a decrease in all investigated cytokines (IL-10, IL-12p70, and IL-1β). Inhibitors of mitochondrial respiration had no effect on rFlaA:Betv1-induced IL-10 level, but either enhanced the secretion of IL-1β (oligomycin) or decreased IL-12p70 (antimycin A). In extracellular flux measurements, mDCs showed a strongly enhanced glycolysis after rFlaA:Betv1 stimulation, which was slightly increased after respiratory shutdown using antimycin A. rFlaA:Betv1-stimulated mDCs secreted directly antimicrobial substances in a mTOR- and fatty acid metabolism-dependent manner. In co-cultures of rFlaA:Betv1-stimulated mDCs with CD4+ T cells, the suppression of Bet v 1-specific TH2 responses was shown to depend on fatty acid synthesis. The effector function of rFlaA:Betv1-activated mDCs mainly relies on glycolysis, with fatty acid synthesis also significantly contributing to rFlaA:Betv1-mediated cytokine secretion, the production of antimicrobial molecules, and the modulation of T cell responses.
Exploring the Concept of In Vivo Guided Tissue Engineering by a Single-Stage Surgical Procedure in a Rodent Model
Authors: Chamorro Clara Ibel , Zeiai Said , Juul Nikolai , Willacy Oliver , Huo Jinxing , Hilborn Jöns , Fossum Magdalena
Published: October 2022

In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in malformation surgery. Autologous micro-epithelium from skin was integrated with plastically compressed collagen and a degradable knitted fabric mesh. Sixty-three scaffolds were implanted in nine rats for histological and mechanical analyses, up to 4 weeks after transplantation. Tissue integration, cell expansion, proliferation, inflammation, strength, and elasticity were evaluated over time in vivo and validated in vitro in a bladder wound healing model. After 5 days in vivo, we observed keratinocyte proliferation on top of the transplant, remodeling of the collagen, and neovascularization within the transplant. At 4 weeks, all transplants were fully integrated with the surrounding tissue. Tensile strength and elasticity were retained during the whole study period. In the in vitro models, a multilayered epithelium covered the defect after 4 weeks. Autologous micro-epithelial transplants allowed for cell expansion and reorganization in vivo without conventional pre-operative in vitro cell propagation. The method was easy to perform and did not require handling outside the operating theater.
Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review
Authors: Wrotek August , Jackowska Teresa
Published: October 2022

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants–RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV–air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.
Analysis of RIOK2 Functions in Mediating the Toxic Effects of Deoxynivalenol in Porcine Intestinal Epithelial Cells
Authors: Gao Zhongcheng , Xu Chao , Fan Hairui , Wang Haifei , Wu Zhengchang , Wu Shenglong , Bao Wenbin
Published: October 2022

Deoxynivalenol (DON) is a type of mycotoxin that threatens human and livestock health. Right open reading frame kinase 2 (RIOK2) is a kinase that has a pivotal function in ribosome maturation and cell cycle progression. This study aims to clarify the role of the RIOK2 gene in DON-induced cytotoxicity regulation in porcine intestinal epithelial cells (IPEC-J2). Cell viability assay and flow cytometry showed that the knockdown of RIOK2 inhibited proliferation and induced apoptosis, cell cycle arrest, and oxidative stress in DON-induced IPEC-J2. Then, transcriptome profiling identified candidate genes and pathways that closely interacted with both DON cytotoxicity regulation and RIOK2 expression. Furthermore, RIOK2 interference promoted the activation of the MAPK signaling pathway by increasing the phosphorylation of ERK and JNK. Additionally, we performed the dual-luciferase reporter and ChIP assays to elucidate that the expression of RIOK2 was influenced by the binding of transcription factor Sp1 with the promoter region. Briefly, the reduced expression of the RIOK2 gene exacerbates the cytotoxic effects induced by DON in IPEC-J2. Our findings provide insights into the control strategies for DON contamination by identifying functional genes and effective molecular markers.
Quantitative Metabolomic Analysis of Changes in the Rat Blood Serum during Autophagy Modulation: A Focus on Accelerated Senescence
Authors: Snytnikova Olga , Tsentalovich Yuri , Sagdeev Renad , Kolosova Nataliya , Kozhevnikova Oyuna
Published: October 2022

Autophagy is involved in the maintenance of cellular homeostasis and the removal of damaged proteins and organelles and is necessary to maintain cell metabolism in conditions of energy and nutrient deficiency. A decrease in autophagic activity plays an important role in age-related diseases. However, the metabolic response to autophagy modulation remains poorly understood. Here, we for the first time explored the effects of (1) autophagy activation by 48 h fasting, (2) inhibition by chloroquine (CQ) treatment, and (3) combined effects of fasting and CQ on the quantitative composition of metabolites in the blood serum of senescent-accelerated OXYS and control Wistar rats at the age of 4 months. By means of high-resolution 1H NMR spectroscopy, we identified the quantitative content of 55 serum metabolites, including amino acids, organic acids, antioxidants, osmolytes, glycosides, purine, and pyrimidine derivatives. Groups of 48 h fasting (induction of autophagy), CQ treatment (inhibition of autophagy), and combined effects (CQ + fasting) are clearly separated from control groups by principal component analysis. Fasting for 48 h led to significant changes in the serum metabolomic profile, primarily affecting metabolic pathways related to fatty acid metabolism, and led to metabolism of several amino acids. Under CQ treatment, the most affected metabolites were citrate, betaine, cytidine, proline, tryptophan, glutamate, and mannose. As shown by two-way ANOVA, for many metabolites the effects of autophagy modulation depend on the animal genotype, indicating a dysregulation of metabolome reactivity in OXYS rats. Thus, the metabolic responses to modulation of autophagy in OXYS rats and Wistar rats are different. Altered metabolites in OXYS rats may serve as potential biomarkers of the manifestation of the signs of accelerated aging. Metabolic signatures characteristic to fasting and CQ treatment revealed in this work might provide a better understanding of the connections between metabolism and autophagy.
Short-Chain Fatty Acids Modulate Sperm Migration through Olfactory Receptor 51E2 Activity
Authors: Teveroni Emanuela , Di Nicuolo Fiorella , Vergani Edoardo , Bruno Carmine , Maulucci Giuseppe , Bianchetti Giada , Astorri Anna Laura , Grande Giuseppe , Gervasoni Jacopo , Santucci Lavinia , De Spirito Marco , Urbani Andrea , Pontecorvi Alfredo , Mancini Francesca , Milardi Domenico
Published: October 2022

The non-orthotopic expression of olfactory receptors (ORs) includes the male reproductive system, and in particular spermatozoa; their active ligands could be essential to sperm chemotaxis and chemical sperm–oocyte communication. OR51E2 expression has been previously reported on sperm cells’ surface. It has been demonstrated in different cellular models that olfactory receptor 51E2 (OR51E2) binds volatile short-chain fatty acids (SCFAs) as specific ligands. In the present research, we make use of Western blot, confocal microscopy colocalization analysis, and the calcium-release assay to demonstrate the activation of sperm cells through OR51E2 upon SCFAs stimulus. Moreover, we perform a novel modified swim-up assay to study the involvement of OR51E2/SCFAs in sperm migration. Taking advantage of computer-assisted sperm analysis (CASA system), we determine the kinematics parameters of sperm cells migrating towards SCFAs-enriched medium, revealing that these ligands are able to promote a more linear sperm-cell orientation. Finally, we obtain SCFAs by mass spectrometry in cervico-vaginal mucus and show for the first time that a direct incubation between cervical mucus and sperm cells could promote their activation. This study can shed light on the possible function of chemosensory receptors in successful reproduction activity, laying the foundation for the development of new strategies for the treatment of infertile individuals.
Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability
Authors: Wang Hongji , Zhang Chaowen , Li Mengnan , Liu Chaoran , Wang Jingyi , Ou Xuan , Han Yuzhu
Published: October 2022

Changes in mitochondrial membrane permeability are closely associated with mitochondria-mediated apoptosis. Antimicrobial peptides (AMPs), which have been found to enter cells to exert physiological effects, cause damage to the mitochondria. This paper reviews the molecular mechanisms of AMP-mediated apoptosis by changing the permeability of the mitochondrial membrane through three pathways: the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM), and mitochondrial permeability transition pore (MPTP). The roles of AMPs in inducing changes in membrane permeability and apoptosis are also discussed. Combined with recent research results, the possible application prospects of AMPs are proposed to provide a theoretical reference for the development of AMPs as therapeutic agents for human diseases.
Non-Histone Lysine Crotonylation Is Involved in the Regulation of White Fat Browning
Authors: Liu Yuexia , Li Yizhou , Liang Juntong , Sun Zhuwen , Sun Chao
Published: October 2022

Lysine crotonylation modification is a novel acylation modification that is similar to acetylation modification. Studies have found that protein acetylation plays an important regulatory part in the occurrence and prevention of obesity and is involved in the regulation of glucose metabolism, tricarboxylic acid cycle, white fat browning and fatty acid metabolism. Therefore, we speculate that protein crotonylation may also play a more vital role in regulating the browning of white fat. To verify this conjecture, we identified 7254 crotonyl modification sites and 1629 modified proteins in iWAT of white fat browning model mice by affinity enrichment and liquid chromatography–mass spectrometry (LC-MS/MS). We selected five representative proteins in the metabolic process, namely glycerol-3-phosphate dehydrogenase 1 (GPD1), fatty acid binding protein 4 (FABP4), adenylate kinase 2 (AK2), triosephosphate isomerase 1 (TPI1) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8). Through qPCR, Western blotting, immunofluorescence staining, Oil Red O staining and HE staining, we demonstrated that GPD1 and FABP4 inhibited white fat browning, while AK2, TPI1 and NDUFA8 promoted white fat browning. GPD1 and FABP4 proteins were downregulated by crotonylation modification, while AK2, TPI1 and NDUFA8 proteins were upregulated by crotonylation modification. Further detection found that the crotonylation modification of GPD1, FABP4, AK2, TPI1 and NDUFA8 promoted white fat browning, which was consistent with the sequencing results. These results indicate that the protein crotonylation is involved in regulating white fat browning, which is of great significance for controlling obesity and treating obesity-related diseases.
Pioglitazone Modifies Kupffer Cell Function and Protects against Escherichia coli-Induced Bacteremia in Burned Mice
Authors: Miyazaki Hiromi , Kinoshita Manabu , Nakashima Hiroyuki , Nakamura Shingo , Saitoh Daizoh
Published: October 2022

Infectious complications and subsequent sepsis in severely burned patients lead to high morbidity and mortality in response to uncontrolled innate immune responses mediated by macrophages. Peroxisome proliferator-activated receptor gamma (PPARγ) has anti-inflammatory activity and acts as a master regulator of macrophage polarization. In this study, we investigated whether the administration of a PPARγ agonist could modulate the Kupffer cell phenotype and thereby ameliorate the dysregulated innate response during post-burn bacterial infection. C57BL/6 mice were subjected to severe burns and randomized to receive either the PPARγ agonist, pioglitazone, or the vehicle control five days after injury, followed by the subsequent analysis of hepatic macrophages. Survival from the bacterial infection was monitored for seven days. Pioglitazone protected burned mice against bacterial infection. A single treatment with pioglitazone significantly enhanced phagocytosis, phagosome acidification, bacterial clearance, and reduction in inflammatory mediators in Kupffer cells. In conclusion, PPARγ activation by pioglitazone prevents clinical deterioration due to post-burn bacterial infection and improves survival. Our findings suggest that pioglitazone may be an effective therapeutic candidate for post-burn infectious complications.
Development and In Vitro and In Vivo Evaluation of an Antineoplastic Copper(II) Compound (Casiopeina III-ia) Loaded in Nonionic Vesicles Using Quality by Design
Authors: Aguilar-Jiménez Zenayda , González-Ballesteros Mauricio , Dávila-Manzanilla Silvia G. , Espinoza-Guillén Adrián , Ruiz-Azuara Lena
Published: October 2022

In recent decades, the interest in metallodrugs as therapeutic agents has increased. Casiopeinas are copper-based compounds that have been evaluated in several tumor cell lines. Currently, casiopeina III-ia (CasIII-ia) is being evaluated in phase I clinical trials. The aim of the present work is to develop a niosome formulation containing CasIII-ia for intravenous administration through a quality-by-design (QbD) approach. Risk analysis was performed to identify the factors that may have an impact on CasIII-ia encapsulation. The developed nanoformulation optimized from the experimental design was characterized by spectroscopy, thermal analysis, and electronic microscopy. In vitro drug release showed a burst effect followed by a diffusion-dependent process. The niosomes showed physical stability for at least three months at 37 °C and 75% relative humidity. The in vitro test showed activity of the encapsulated CasIII-ia on a metastatic breast cancer cell line and the in vivo test of nanoencapsulated CasIII-ia maintained the activity of the free compound, but showed a diminished toxicity. Therefore, the optimal conditions obtained by QbD may improve the scaling-up process.