bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecasting Carbon Price in China: A Multimodel Comparison
Authors: Li Houjian , Huang Xinya , Zhou Deheng , Cao Andi , Su Mengying , Wang Yufeng , Guo Lili
Published: May 2022

With the global concern for carbon dioxide, the carbon emission trading market is becoming more and more important. An accurate forecast of carbon price plays a significant role in understanding the dynamics of the carbon trading market and achieving national emission reduction targets. Carbon prices are influenced by many factors, which makes carbon price forecasting a complicated problem. In recent years, deep learning models are widely used in price forecasting, because they have high forecasting accuracy when dealing with nonlinear time series data. In this paper, Multivariate Long Short-Term Memory (LSTM) in deep learning is used to forecast carbon prices in China, which takes into account the factors affecting the carbon price. The historical time series data of carbon prices in Hubei (HBEA) and Guangdong (GDEA) and three traditional energy prices affecting carbon prices from 5 May 2014 to 22 July 2021 are collected to form two data sets. To prove the forecast effect of our model, this paper not only uses Multivariate LSTM, Multilayer Perceptron (MLP), Support Vector Regression (SVR), and Recurrent Neural Network (RNN) to forecast the same data, but also compares the forecast results of Multivariate LSTM with the existing research on HBEA and GDEA forecast based on deep learning recently. The results show that the MAE, MSE, and RMSE obtained by the Multivariate LSTM are all smaller than other prediction models, which proves that the model is more suitable for carbon price forecast and offers a new approach to carbon prices forecast. This research conclusion also provides some policy implications.
Is It Possible to Predict the Length of Stay of Patients Undergoing Hip-Replacement Surgery?
Authors: Trunfio Teresa Angela , Borrelli Anna , Improta Giovanni
Published: May 2022

The proximal fracture of the femur and hip is the most common reason for hospitalization in orthopedic departments. In Italy, 115,989 hip-replacement surgeries were performed in 2019, showing the economic relevance of studying this type of procedure. This study analyzed the data relating to patients who underwent hip-replacement surgery in the years 2010–2020 at the “San Giovanni di Dio e Ruggi d’Aragona” University Hospital of Salerno. The multiple linear regression (MLR) model and regression and classification algorithms were implemented in order to predict the total length of stay (LOS). Lastly, using a statistical analysis, the impact of COVID-19 was evaluated. The results obtained from the regression analysis showed that the best model was MLR, with an R2 value of 0.616, compared with XGBoost, Gradient-Boosted Tree, and Random Forest, with R2 values of 0.552, 0.543, and 0.448, respectively. The t-test showed that the variables that most influenced the LOS, with the exception of pre-operative LOS, were gender, age, anemia, fracture/dislocation, and urinary disorders. Among the classification algorithms, the best result was obtained with Random Forest, with a sensitivity of the longest LOS of over 89%. In terms of the overall accuracy, Random Forest and Gradient-Boosted Tree achieved a value of 71.76% and an error of 28.24%, followed by Decision Tree, with an accuracy of 71.13% and an error of 28.87%, and, finally, Support Vector Machine, with an accuracy of 65.06% and an error of 34.94%. A significant difference in cardiovascular disease, fracture/dislocation, and post-operative LOS variables was shown by the chi-squared test and Mann–Whitney test in the comparison between 2019 (before COVID-19) and 2020 (in full pandemic emergency conditions).
Informality, Social Citizenship, and Wellbeing among Migrant Workers in Costa Rica in the Context of COVID-19
Authors: Poirier Mathieu J. P. , Barraza Douglas , Caxaj C. Susana , Martínez Ana María , Hard Julie , Montoya Felipe
Published: May 2022

Costa Rica is home to 557,000 migrants, whose disproportionate exposure to precarious, dangerous, and informal work has resulted in persistent inequities in health and wellbeing in the midst of the COVID-19 pandemic. We used a novel multimodal grounded approach synthesizing documentary film, experiential education, and academic research to explore socioecological wellbeing among Nicaraguan migrant workers in Costa Rica. Participants pointed to the COVID-19 pandemic as exacerbating the underlying conditions of vulnerability, such as precarity and informality, dangerous working conditions, social and systemic discrimination, and additional burdens faced by women. However, the narrative that emerged most consistently in shaping migrants’ experience of marginalization were challenges in obtaining documentation—both in the form of legal residency and health insurance coverage. Our results demonstrate that, in spite of Costa Rica’s acclaimed social welfare policies, migrant workers continue to face exclusion due to administrative, social, and financial barriers. These findings paint a rich picture of how multiple intersections of precarious, informal, and dangerous working conditions; social and systemic discrimination; gendered occupational challenges; and access to legal residency and health insurance coverage combine to prevent the full achievement of a shared minimum standard of social and economic security for migrant workers in Costa Rica.
Causes of Shoulder Dysfunction in Diabetic Patients: A Review of Literature
Authors: Struyf Filip , Mertens Michel , Navarro-Ledesma Santiago
Published: May 2022

Objective: Understanding the underlying mechanisms behind shoulder dysfunctions in patients with diabetes mellitus. Study Design: Systematic qualitative literature review. Participants: Patients with shoulder dysfunctions and diagnosed with impaired glucose tolerance or diabetes mellitus. Intervention: Published scientific literature containing evidence about the mechanisms of shoulder dysfunctions in the diabetic population. Articles were selected based on criteria containing diabetic population, shoulder dysfunction, methodological quality ≥ 6/9 and >20 subjects. Main Outcome measures: range of motion; questionnaires (QoL, UCLA-m, SPADI, DASH); blood glucose, blood HbA1C; calculated capsular stiffness (Kcap); calcification shoulder joint; shoulder dysfunction in patients with glucose metabolism disorders and diabetes mellitus. Results: We found 17 published articles with level 2 and 3 evidence. Multiple factors such as age, duration of diabetes mellitus (DM), glycated hemoglobin (HbA1c), advanced glycation end products (AGE), vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß) were shown to be associated with tendon changes and increased capsular stiffness (Kcap) conceivably leading to limited range of motion (ROM) or frozen shoulder. Decreased ROM and frozen shoulder have a significantly higher prevalence in DM than in non-DM. Conclusions: Based on the current literature we confirm a high prevalence of shoulder dysfunctions in patients with diabetes mellitus. The cause of the shoulder complications is unknown, and more research is mandatory to shed more light on the complex interplay between the multifactorial causes of shoulder dysfunction in diabetes mellitus.
Sibling Separation Due to Parental Divorce: Diagnostic Aspects
Authors: Lewandowska-Walter Aleksandra , Błażek Magdalena
Published: May 2022

Separation of siblings is one of the most difficult diagnostic problems faced by psychologists. Such situations are happening more often in the face of the increasing number of divorces and breakdown of relationships. Therefore, a diagnostic task becomes an in-depth assessment of intra-family relationships, ties connecting family members, the preferences of individual people and predicting the long-term consequences of the proposed solutions. The article is dedicated to this problem, and the issue is addressed through the theoretical perspective and the analysis of two cases, i.e., the situation of separated siblings. In the study of children, we present a relatively new method, based on the authors’ clinical experience, which could be used to diagnose the family situation of children. The first goal was to analyze the reasons for the separation of siblings whose parents were in conflict during the separation (first case study) and after the separation (second case study), as well as to assess the functioning of the children resulting from the family breakdown, and the decision to separate them from siblings. The analysis allowed identifying the areas of sibling functioning, which should become the subject of diagnosis when working on expert opinions in divorce cases, or cases establishing contact between parents and children. The second aim of the report was to assess the effectiveness of using play as a diagnostic method in a situation that is a source of stress for the child (family breakdown) and causes tension (the diagnostic process in which this topic is discussed).
The Impact of Information Presentation and Cognitive Dissonance on Processing Systematic Review Summaries: A Randomized Controlled Trial on Bicycle Helmet Legislation
Authors: Béchard Benoît , Kimmerle Joachim , Lawarée Justin , Bédard Pierre-Oliver , Straus Sharon E. , Ouimet Mathieu
Published: May 2022

Background: Summaries of systematic reviews are a reference method for the dissemination of research evidence on the effectiveness of public health interventions beyond the scientific community. Motivated reasoning and cognitive dissonance may interfere with readers’ ability to process the information included in such summaries. Methods: We conducted a web experiment on a panel of university-educated North Americans (N = 259) using a systematic review of the effectiveness of bicycle helmet legislation as a test case. The outcome variables were the perceived tentativeness of review findings and attitude toward bicycle helmet legislation. We manipulated two types of uncertainty: (i) deficient uncertainty (inclusion vs. non-inclusion of information on limitations of the studies included in the review) and (ii) consensus uncertainty (consensual findings showing legislation effectiveness vs. no evidence of effectiveness). We also examined whether reported expertise in helmet legislation and the frequency of wearing a helmet while cycling interact with the experimental factors. Results: None of the experimental manipulations had a main effect on the perceived tentativeness. The presentation of consensual efficacy findings had a positive main effect on the attitude toward the legislation. Self-reported expertise had a significant main effect on the perceived tentativeness, and exposing participants with reported expertise to results showing a lack of evidence of efficacy increased their favorable attitude toward the legislation. Participants’ helmet use was positively associated with their attitude toward the legislation (but not with perceived tentativeness). Helmet use did not interact with the experimental manipulations. Conclusions: Motivated reasoning and cognitive dissonance influence a reader’s ability to process information contained in a systematic review summary.
Physical Activity and Sports Participation among Adolescents: Associations with Sports-Related Knowledge and Attitudes
Authors: Oja Leila , Piksööt Jaanika
Published: May 2022

The impact of physical activity and sport on the development of adolescents’ knowledge and attitudes has not been studied sufficiently. We assume that young people with more knowledge of sports will continue to be physically active on their own. The aim of this study is to identify the differences in the sports and physical activity-related knowledge and attitudes of adolescents who engage in organised sports training and those who do not. A total of 1033 6th-grade students from (aged 12.7 ± 0.4 years) 52 schools in Estonia were involved in the study. Logistic regression analysis was used to examine the associations between sports-related knowledge and attitudes towards students participating in organised sports training. The main reasons which hindered adolescents from being active were a lack of suitable equipment, being weaker than others, and laziness. Knowledge of physical activity, higher perceived benefits, and lower barriers to physical activity were the predictors contributing to adolescents’ participation in sports training. The results demonstrated that physically active students have better knowledge of sports and physical activity. Students participating in organised sports training have strong positive benefits from being regularly physically active and feel that sports training maintains their health.
The Association between Postpartum Pelvic Girdle Pain and Pelvic Floor Muscle Function, Diastasis Recti and Psychological Factors—A Matched Case-Control Study
Authors: Starzec-Proserpio Małgorzata , Rejano-Campo Montserrat , Szymańska Agata , Szymański Jacek , Baranowska Barbara
Published: May 2022

There is uncertainty regarding the association between abdominal morphology, pelvic floor function, and psychological factors in women with postpartum pelvic girdle pain (PGP). The aim of this case-control study was to evaluate the differences between women with and without persistent PGP regarding pelvic floor function, diastasis recti, and psychological factors 6–24 weeks postpartum. Pelvic floor manometry, palpation examination of abdominal muscles, the International Consultation on Incontinence Questionnaire Short Form, The Depression, Anxiety and Stress Scale—21, and the Pain Catastrophizing Scale were used. The PGP group presented with lower vaginal resting pressure (p < 0.001), more tenderness (p = 0.018) and impaired voluntary activation of pelvic floor muscles (p ≤ 0.001). Women with pain also had more distortion on the level of the anterior abdominal wall (p = 0.001) and more severe diastasis recti (p = 0.046) when compared to pain-free controls. Lower vaginal resting pressure was the strongest factor explaining PGP (OR 0.702, 95%CI 0.502–0.981). There were no differences in terms of the pelvic floor strength, endurance, severity of urinary incontinence and reported distress between the groups. Women with PGP 6–24 weeks postpartum differ in pelvic floor and abdominal muscle function from the pain-free controls. Vaginal resting pressure may be an important factor in pelvic girdle pain shortly postpartum. Further studies are needed to see a trend in changes over time.
Modification Effect of PARP4 and ERCC1 Gene Polymorphisms on the Relationship between Particulate Matter Exposure and Fasting Glucose Level
Authors: Kim Jin Hee , Lee Seungho , Hong Yun-Chul
Published: May 2022

Particulate matter (PM) has been linked to adverse health outcomes, including insulin resistance (IR). To evaluate the relationships between exposures to PM10, PM2.5–10, and PM2.5; the serum level of fasting glucose, a key IR indicator; and effects of polymorphisms of two repair genes (PARP4 and ERCC1) on these relations, PMs exposure data and blood samples for glucose measurement and genotyping were collected from 527 Korean elders. Daily average levels of PMs during 8 days, from 7 days before examination to the health examination day (from lag day 7 to lag day 0), were used for association analyses, and mean concentrations of PM10, PM2.5–10, and PM2.5 during the study period were 43.4 µg/m3, 19.9 µg/m3, and 23.6 µg/m3, respectively. All three PMs on lag day 4 (mean, 44.5 µg/m3 for PM10, 19.9 µg/m3 for PM2.5–10, and 24.3 µg/m3 for PM2.5) were most strongly associated with an increase in glucose level (percent change by inter-quartile range-change of PM: (β) = 1.4 and p = 0.0023 for PM10; β = 3.0 and p = 0.0010 for PM2.5–10; and β = 2.0 and p = 0.0134 for PM2.5). In particular, elders with PARP4 G-C-G or ERCC1 T-C haplotype were susceptible to PMs exposure in relation to glucose levels (PARP4 G-C-G: β = 2.6 and p = 0.0006 for PM10, β = 3.5 and p = 0.0009 for PM2.5–10, and β = 1.6 and p = 0.0020 for PM2.5; ERCC1 T-C: β = 2.2 and p = 0.0016 for PM10, β = 3.5 and p = 0.0003 for PM2.5–10, and β = 1.2 and p = 0.0158 for PM2.5). Our results indicated that genetic polymorphisms of PARP4 and ERCC1 could modify the relationship between PMs exposure and fasting glucose level in the elderly.
Who Became Lonely during the COVID-19 Pandemic? An Investigation of the Socioeconomic Aspects of Loneliness in Japan
Authors: Khan Mostafa Saidur Rahim , Yuktadatta Pattaphol , Kadoya Yoshihiko
Published: May 2022

The COVID-19 pandemic has impacted social and economic aspects of people’s lives in different ways, causing them to experience different levels of loneliness. This study examines the extent of loneliness among men and women of various ages in Japan during the pandemic and attempts to determine the underlying causes. We used data from Hiroshima University’s nationwide survey conducted before and during the pandemic in Japan. The sample consists of 3755 participants, of which 67% are men and 33% are women with an average age of 51 years (SD = 13.64). Using mean comparison tests and probit regression models, we show that loneliness is a common occurrence among the Japanese population and that a significant number of people became lonely for the first time during the pandemic. In general, loneliness was greater among younger respondents, but older people became lonelier during the pandemic. Simultaneously, we observed significant differences in loneliness across age and gender subsamples. Although depression and subjective health status contributed to loneliness, we found no single explanation for the loneliness experienced by people during the pandemic; rather, subsample analysis revealed that the causes of loneliness for each group differed. Nevertheless, we discovered that older people are at a higher risk of developing loneliness during the pandemic due to a variety of socioeconomic and behavioral factors. The findings of this study suggest that health authorities should not generalize cases of loneliness, but rather intervene individually in each group to avoid further complications.
Factors Associated with the Participation of Older Adults in Cultural and Sports Activities
Authors: Ghența Mihaela , Matei Aniela , Mladen-Macovei Luise , Bobârnat Elen-Silvana
Published: May 2022

In the context of population aging, we have witnessed an increased interest in studying the participation of older persons in cultural and sport activities. The aim of this paper is to identify the participation rate in cultural and sports activities among Romanian older adults and the sociodemographics/behavioral variables that correlate with the participation rate in cultural and sports activities. In order to answer our research questions, we employed a questionnaire-based survey, and we used a nationally representative sample. Results point to low participation in both cultural and sports activities. Gender, residence, education, income, degree of mobility, internet connection, and availability of financial resources are significant variables that correlate with the engagement of older people in cultural and sports activities. Our study could serve as a base for concrete policy measures in the field of health and social inclusion of older persons.
Growth Targets Management, Regional Competition and Urban Land Green Use Efficiency According to Evidence from China
Authors: Liu Zhangsheng , Lai Binbin , Wu Shuangyin , Liu Xiaotian , Liu Qunhong , Ge Kun
Published: May 2022

Based on the panel data of 257 prefecture-level cities in China from 2010 to 2017, this paper measured urban land green use efficiency (ULGUE), incorporating undesirable outputs, via the super efficiency slack-based model (SBM). It also explored the effect, mechanism, and heterogeneity of growth targets management and regional competition on ULGUE via the time-varying gravitational spatial weight matrix and the spatial self-lagging model. The results show that growth targets management and regional competition have significant positive effects on ULGUE, and enhance the ULGUE by promoting local investment attraction, increasing innovation inputs, optimizing environmental regulations and strengthening commercial activities. Additionally, growth targets management has a more significant effect on eastern cities, non-central cities, and mature urban agglomeration, while regional competition has a more significant effect on central cities, non-central cities, and developmental urban agglomeration. Therefore, considering development as the priority, setting relatively aggressive economic growth targets and optimizing the regional competition mechanism for growth targets management can help improve the ULGUE and promote high-quality economic development in China.
Impact of Carbon Tax and Subsidy Policies on Original Equipment Manufacturers and Remanufacturing Companies from the Perspective of Carbon Emissions
Authors: Zhao Shuiying , Xu Yi , Liu Conghu , Wei Fangfang
Published: May 2022

To analyze the impact of government carbon tax and subsidy policies on the manufac turing industry in the context of carbon peaking and carbon neutrality. This paper constructs a game model based on two government policies: a “carbon tax” policy for the original product and a “subsidy” policy for the remanufactured product, taking the original product and the remanufactured product as the objects. The policy game model is used to study the impact of carbon taxes, government subsidies, and carbon emissions on product quality, sales, and corporate profits. The results show that under the carbon tax and government subsidy policies, the price of remanufactured products will decrease, the quality will increase, sales will improve, and remanufacturers’ profits will increase; these outcomes are conducive to the development of remanufacturing enterprises. Meanwhile, the price of original products will increase, quality will decrease, sales will decline, and original equipment manufacturers will have to develop and adopt low-carbon technologies to achieve sustainable development. This paper provides decision support for the formulation of government carbon emission policy, and theories and methods for the sustainable development of the manufacturing industry.
Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma
Authors: Luo Sheng-Dean , Tsai Hsin-Ting , Chiu Tai-Jan , Li Shau-Hsuan , Hsu Ya-Ling , Su Li-Jen , Tsai Meng-Hsiu , Lee Ching-Yi , Hsiao Chang-Chun , Chen Chang-Han
Published: May 2022

Leptin is a crucial regulator of metabolism and energy homeostasis in mammals. Many studies have investigated the impacts of leptin on human cancers, such as proliferation and metastasis. However, the mechanisms underlying leptin-mediated regulation of lipid metabolism in nasopharyngeal carcinoma (NPC) remain incompletely understood. In the current study, leptin downregulation ameliorated lipid accumulation, triglyceride, and cholesterol levels. Mechanistically, diminished leptin by siRNA not only inhibited sterol regulatory element-binding protein 1 (SREBP1), a master regulator of lipid metabolism, at the mRNA and protein levels, but also reduced SREBP1 downstream target expressions, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1), in NPC cells. In addition, leptin expression could modulate the promoter activity of SREBP1. We also found that pharmacological inhibition of poly-ADP ribose polymerase-γ (PPAR-γ) resulted in increased SREBP1 expression in leptin-depleted NPC cells. Functionally, SREBP1 overexpression overcame the effects of leptin-silencing attenuated triglyceride level, cholesterol level and cell survival in NPC cells. Taken together, our results demonstrate that leptin is an important regulator of lipid metabolism in NPC cells and might could be a potential therapeutic target for treatment of NPC patients.
Current Insights on the Impact of Proteomics in Respiratory Allergies
Authors: Vizuet-de-Rueda Juan Carlos , Montero-Vargas Josaphat Miguel , Galván-Morales Miguel Ángel , Porras-Gutiérrez-de-Velasco Raúl , Teran Luis M.
Published: May 2022

Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders’ pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.
Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients
Authors: Kavec Miriam J. , Urbanova Marketa , Makovicky Pavol , Opattová Alena , Tomasova Kristyna , Kroupa Michal , Kostovcikova Klara , Siskova Anna , Navvabi Nazila , Schneiderova Michaela , Vymetalkova Veronika , Vodickova Ludmila , Vodicka Pavel
Published: May 2022

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well.
CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion
Authors: Soriano-Romaní Laura , Mir Fayaz A. , Singh Niharika , Chin Ian , Hafezi-Moghadam Ali , Masli Sharmila
Published: May 2022

To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.
Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking
Authors: Melnik Tamara , Ben Ameur Senda , Kanfar Nasreddine , Vinet Laurent , Delie Florence , Jordan Olivier
Published: May 2022

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications.
Molecular Dynamics Simulations Reveal Structural Interconnections within Sec14-PH Bipartite Domain from Human Neurofibromin
Authors: Rizza Fabio , Vertemara Jacopo , Tisi Renata
Published: May 2022

Neurofibromin, the main RasGAP in the nervous system, is a 2818 aa protein with several poorly characterized functional domains. Mutations in the NF1-encoding gene lead to an autosomal dominant syndrome, neurofibromatosis, with an incidence of 1 out of 3000 newborns. Missense mutations spread in the Sec14-PH-encoding sequences as well. Structural data could not highlight the defect in mutant Sec14-PH functionality. By performing molecular dynamics simulations at different temperatures, we found that the lid-lock is fundamental for the structural interdependence of the NF1 bipartite Sec14-PH domain. In fact, increased flexibility in the lid-lock loop, observed for the K1750Δ mutant, leads to disconnection of the two subdomains and can affect the stability of the Sec14 subdomain.
Heme Oxygenase Modulation Drives Ferroptosis in TNBC Cells
Authors: Consoli Valeria , Sorrenti Valeria , Pittalà Valeria , Greish Khaled , D’Amico Agata Grazia , Romeo Giuseppe , Intagliata Sebastiano , Salerno Loredana , Vanella Luca
Published: May 2022

The term ferroptosis refers to a peculiar type of programmed cell death (PCD) mainly characterized by extensive iron-dependent lipid peroxidation. Recently, ferroptosis has been suggested as a potential new strategy for the treatment of several cancers, including breast cancer (BC). In particular, among the BC subtypes, triple negative breast cancer (TNBC) is considered the most aggressive, and conventional drugs fail to provide long-term efficacy. In this context, our study’s purpose was to investigate the mechanism of ferroptosis in breast cancer cell lines and reveal the significance of heme oxygenase (HO) modulation in the process, providing new biochemical approaches. HO’s effect on BC was evaluated by MTT tests, gene silencing, Western blot analysis, and measurement of reactive oxygen species (ROS), glutathione (GSH) and lipid hydroperoxide (LOOH) levels. In order to assess HO’s implication, different approaches were exploited, using two distinct HO-1 inducers (hemin and curcumin), a well-known HO inhibitor (SnMP) and a selective HO-2 inhibitor. The data obtained showed HO’s contribution to the onset of ferroptosis; in particular, HO-1 induction seemed to accelerate the process. Moreover, our results suggest a potential role of HO-2 in erastin-induced ferroptosis. In view of the above, HO modulation in ferroptosis can offer a novel approach for breast cancer treatment.
MAEBL Contributes to Plasmodium Sporozoite Adhesiveness
Authors: Sá Mónica , Costa David Mendes , Teixeira Ana Rafaela , Pérez-Cabezas Begoña , Formaglio Pauline , Golba Sylvain , Sefiane-Djemaoune Hélèna , Amino Rogerio , Tavares Joana
Published: May 2022

The sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical diseases in children, impelling a continuous search for novel candidates. In this work, we studied the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) for infection by Plasmodium sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces Plasmodium berghei hemolymph sporozoite infectivity to mice. Moreover, we found that maebl knockout (maebl-) sporozoites display reduced adhesion, including to cultured hepatocytes, which could contribute to the defects in multiple biological processes, such as in gliding motility, hepatocyte wounding, and invasion. The maebl- defective phenotypes in mosquito salivary gland and liver infection were reverted by genetic complementation. Using a parasite line expressing a C-terminal myc-tagged MAEBL, we found that MAEBL levels peak in midgut and hemolymph parasites but drop after sporozoite entry into the salivary glands, where the labeling was found to be heterogeneous among sporozoites. MAEBL was found associated, not only with micronemes, but also with the surface of mature sporozoites. Overall, our data provide further insight into the role of MAEBL in sporozoite infectivity and may contribute to the design of future immune interventions.
Water-Soluble, Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells
Authors: Ren Haiyuan , Li Jinrui , Peng Ai , Liu Ting , Chen Mengjun , Li Hongguang , Wang Xiaojing
Published: May 2022

As carbon-based nanomaterials, water-soluble C60 derivatives have potential applications in various fields of biomedicine. In this study, a water-soluble fullerene C60 derivative bearing alanine residues (Ala-C60) was synthesized. The effects of Ala-C60 on neural stem cells (NSCs) as seed cells were explored. Ala-C60 can promote the proliferation of NSCs, induce NSCs to differentiate into neurons, and inhibit the migration of NSCs. Most importantly, the Ala-C60 can significantly increase the cell viability of NSCs treated with hydrogen peroxide (H2O2). The glutathioneperoxidase (GSH-Px) and superoxide dismutase (SOD) activities and glutathione (GSH) content increased significantly in NSCs treated even by 20 μM Ala-C60. These findings strongly indicate that Ala-C60 has high potential to be applied as a scaffold with NSCs for regeneration in nerve tissue engineering for diseases related to the nervous system.
Reprogramming of Plant Central Metabolism in Response to Abiotic Stresses: A Metabolomics View
Authors: Xu Yuan , Fu Xinyu
Published: May 2022

Abiotic stresses rewire plant central metabolism to maintain metabolic and energy homeostasis. Metabolites involved in the plant central metabolic network serve as a hub for regulating carbon and energy metabolism under various stress conditions. In this review, we introduce recent metabolomics techniques used to investigate the dynamics of metabolic responses to abiotic stresses and analyze the trend of publications in this field. We provide an updated overview of the changing patterns in central metabolic pathways related to the metabolic responses to common stresses, including flooding, drought, cold, heat, and salinity. We extensively review the common and unique metabolic changes in central metabolism in response to major abiotic stresses. Finally, we discuss the challenges and some emerging insights in the future application of metabolomics to study plant responses to abiotic stresses.
Current Perspectives on Synthetic Compartments for Biomedical Applications
Authors: Heuberger Lukas , Korpidou Maria , Eggenberger Olivia M. , Kyropoulou Myrto , Palivan Cornelia G.
Published: May 2022

Nano- and micrometer-sized compartments composed of synthetic polymers are designed to mimic spatial and temporal divisions found in nature. Self-assembly of polymers into compartments such as polymersomes, giant unilamellar vesicles (GUVs), layer-by-layer (LbL) capsules, capsosomes, or polyion complex vesicles (PICsomes) allows for the separation of defined environments from the exterior. These compartments can be further engineered through the incorporation of (bio)molecules within the lumen or into the membrane, while the membrane can be decorated with functional moieties to produce catalytic compartments with defined structures and functions. Nanometer-sized compartments are used for imaging, theranostic, and therapeutic applications as a more mechanically stable alternative to liposomes, and through the encapsulation of catalytic molecules, i.e., enzymes, catalytic compartments can localize and act in vivo. On the micrometer scale, such biohybrid systems are used to encapsulate model proteins and form multicompartmentalized structures through the combination of multiple compartments, reaching closer to the creation of artificial organelles and cells. Significant progress in therapeutic applications and modeling strategies has been achieved through both the creation of polymers with tailored properties and functionalizations and novel techniques for their assembly.
Precision Nephrology in Patients with Diabetes and Chronic Kidney Disease
Authors: Provenzano Michele , Maritati Federica , Abenavoli Chiara , Bini Claudia , Corradetti Valeria , La Manna Gaetano , Comai Giorgia
Published: May 2022

Diabetes is the leading cause of kidney failure and specifically, diabetic kidney disease (DKD) occurs in up to 30% of all diabetic patients. Kidney disease attributed to diabetes is a major contributor to the global burden of the disease in terms of clinical and socio-economic impact, not only because of the risk of progression to End-Stage Kidney Disease (ESKD), but also because of the associated increase in cardiovascular (CV) risk. Despite the introduction of novel treatments that allow us to reduce the risk of future outcomes, a striking residual cardiorenal risk has been reported. This risk is explained by both the heterogeneity of DKD and the individual variability in response to nephroprotective treatments. Strategies that have been proposed to improve DKD patient care are to develop novel biomarkers that classify with greater accuracy patients with respect to their future risk (prognostic) and biomarkers that are able to predict the response to nephroprotective treatment (predictive). In this review, we summarize the principal prognostic biomarkers of type 1 and type 2 diabetes and the novel markers that help clinicians to individualize treatments and the basis of the characteristics that predict an optimal response.
Genome-Wide Identification and Expression Analyses of the Aquaporin Gene Family in Passion Fruit (Passiflora edulis), Revealing PeTIP3-2 to Be Involved in Drought Stress
Authors: Song Shun , Zhang Dahui , Ma Funing , Xing Wenting , Huang Dongmei , Wu Bin , Chen Jian , Chen Di , Xu Binqiang , Xu Yi
Published: May 2022

Aquaporins (AQPs) in plants can transport water and small molecules, and they play an important role in plant development and abiotic stress response. However, to date, a comprehensive study on AQP family members is lacking. In this study, 27 AQP genes were identified from the passion fruit genome and classified into four groups (NIP, PIP, TIP, SIP) on the basis of their phylogenetic relationships. The prediction of protein interactions indicated that the AQPs of passion fruit were mainly associated with AQP family members and boron protein family genes. Promoter cis-acting elements showed that most PeAQPs contain light response elements, hormone response elements, and abiotic stress response elements. According to collinear analysis, passion fruit is more closely related to Arabidopsis than rice. Furthermore, three different fruit ripening stages and different tissues were analyzed on the basis of the transcriptome sequencing results for passion fruit AQPs under drought, high-salt, cold and high-temperature stress, and the results were confirmed by qRT-PCR. The results showed that the PeAQPs were able to respond to different abiotic stresses, and some members could be induced by and expressed in response to multiple abiotic stresses at the same time. Among the three different fruit ripening stages, 15 AQPs had the highest expression levels in the first stage. AQPs are expressed in all tissues of the passion fruit. One of the passion fruit aquaporin genes, PeTIP3-2, which was induced by drought stress, was selected and transformed into Arabidopsis. The survival rate of transgenic plants under drought stress treatment is higher than that of wild-type plants. The results indicated that PeTIP3-2 was able to improve the drought resistance of plants. Our discovery lays the foundation for the functional study of AQPs in passion fruit.
The First Homologous Expression System for the β-Lytic Protease of Lysobacter capsici VKM B-2533T, a Promising Antimicrobial Agent
Authors: Kudryakova Irina , Afoshin Alexey , Leontyevskaya Elena , Leontyevskaya (Vasilyeva) Natalia
Published: May 2022

A successful homologous expression system based on Lysobacter capsici VKM B-2533T and the plasmid pBBR1-MCS5 was first developed for a promising bacteriolytic enzyme of this bacterium, β-lytic protease (Blp). In the expression strains, blp gene expression under the regulation of the GroEL(A) and T5 promoters increased by 247- and 667-fold, respectively, as compared with the wild-type strain. After the cultivation of the expression strains L. capsici PGroEL(A)-blp and L. capsici PT5-blp, the Blp yield increased by 6.7- and 8.5-fold, respectively, with respect to the wild-type strain. The cultivation of the expression strain L. capsici PT5-blp was successfully scaled up. Under fermentation conditions the yield of the enzyme increased by 1.6-fold. The developed homologous system was used to express the gene of the bacteriolytic serine protease (Serp) of L. capsici VKM B-2533T. The expression of the serp gene in L. capsici PT5-serp increased by 585-fold. The developed homologous system for the gene expression of bacteriolytic Lysobacter enzymes is potentially biotechnologically valuable, and is promising for creating highly efficient expression strains.
Investigation of Brain Function-Related Myokine Secretion by Using Contractile 3D-Engineered Muscle
Authors: Sugimoto Takeshi , Nakamura Tomohiro , Yokoyama Sho , Fujisato Toshia , Konishi Satoshi , Hashimoto Takeshi
Published: May 2022

Brain function-related myokines, such as lactate, irisin, and cathepsin B (CTSB), are upstream factors that control brain-derived neurotrophic factor (BDNF) expression and are secreted from skeletal muscle by exercise. However, whether irisin and CTSB are secreted by muscle contraction remains controversial. Three-dimensional (3D)-engineered muscle (3D-EM) may help determine whether skeletal muscle contraction leads to the secretion of irisin and CTSB, which has never been identified with the addition of drugs in conventional 2D muscle cell cultures. We aimed to investigate the effects of electrical pulse stimulation (EPS)-evoked muscle contraction on irisin and CTSB secretion in 3D-EM. The 3D-EM, which consisted of C2C12 myoblasts and type-1 collagen gel, was allowed to differentiate for 2 weeks and divided into the control and EPS groups. EPS was applied at 13 V, 66 Hz, and 2 msec for 3 h (on: 5 s/off: 5 s). Irisin and CTSB secretion into the culture medium was measured by Western blotting. Irisin secretion was significantly increased following EPS (p < 0.05). However, there was no significant difference in CTSB secretion between the two groups. The present study suggests that irisin may be a contractile muscle-derived myokine, but CTSB is not secreted by EPS-evoked muscle contractile stimulation in 3D-EM.
Full-Length Transcriptome Sequencing Reveals the Impact of Cold Stress on Alternative Splicing in Quinoa
Authors: Zheng Ling , Zhao Yiwu , Gan Yifeng , Li Hao , Luo Shiqi , Liu Xiang , Li Yuanyuan , Shao Qun , Zhang Hui , Zhao Yanxiu , Ma Changle
Published: May 2022

Quinoa is a cold-resistant and nutrient-rich crop. To decipher the cold stress response of quinoa, the full-length transcriptomes of the cold-resistant quinoa variety CRQ64 and the cold-sensitive quinoa variety CSQ5 were compared. We identified 55,389 novel isoforms and 6432 novel genes in these transcriptomes. Under cold stress, CRQ64 had more differentially expressed genes (DEGs) and differentially alternative splicing events compared to non-stress conditions than CSQ5. DEGs that were specifically present only in CRQ64 were significantly enriched in processes which contribute to osmoregulation and ROS homeostasis in plants, such as sucrose metabolism and phenylpropanoid biosynthesis. More genes with differential alternative splicing under cold stress were enriched in peroxidase functions in CRQ64. In total, 5988 transcription factors and 2956 long non-coding RNAs (LncRNAs) were detected in this dataset. Many of these had altered expression patterns under cold stress compared to non-stress conditions. Our transcriptome results demonstrate that CRQ64 undergoes a wider stress response than CSQ5 under cold stress. Our results improved the annotation of the quinoa genome and provide new insight into the mechanisms of cold resistance in quinoa.