bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Sustainable Development of Culture into Tourist Map Design: A Case from Foshan, China
Authors: Zhou Liting , Ouyang Fei , Sun Yan , Chen Wentao , Li Yiyong , Zhao Ruyu
Published: October 2022

As the fourth pillar of sustainable development, culture is widely recognized as contributing to human wellbeing. The distinctive culture of cities is an important driving force for attracting visitors to destinations for tourism consumption. Since historical cities have important cultural and historical values, the design of their tourist maps needs not only geographic positioning and artistic aesthetics, but also a systematic design method to present the connotation of regional cultures, so as to enhance the local cultural identity of hosts and the cultural cognition of visitors, and to drive the local tourism economy, improve the regional environment, promote cultural transmission and inheritance with the help of tourist map design in terms of cultural sustainability, which ultimately achieves sustainable development of human wellbeing. Taking Foshan, a national historical city, as an example, combined with the cultural gene and the cultural hierarchy theory, this study analyzes and summarizes the regional culture of Foshan from three aspects: material cultural gene, intangible cultural gene and spiritual cultural gene. This study also comprehensively presents the geographical information and historical or humanistic characteristics of the city through direct translation, narrative translation, and metaphor translation, which provide theoretical support and practical guidance for the integration of regional cultures into tourist map design.
Assessing Cyberbullying in Adolescence: New Evidence for the Spanish Version of the European Cyberbullying Intervention Project Questionnaire (ECIP-Q)
Authors: Álvarez-Marín Ildefonso , Pérez-Albéniz Alicia , Lucas-Molina Beatriz , Martínez-Valderrey Vanesa , Fonseca-Pedrero Eduardo
Published: October 2022

The prevention of cyberbullying at school requires assessing its prevalence by means of brief measurement instruments with adequate psychometric properties. The present study aims to study the psychometric properties of the European Cyberbullying Intervention Project Questionnaire (ECIP-Q) in a sample of 1777 Spanish adolescents (54.1% women, M = 15.71 years; SD = 1.26), selected by stratified random cluster sampling. The two-factor model (victimization and aggression) displayed appropriate goodness of-fit indices. Configural measurement invariance model across gender was found. The omega reliability coefficient for the victimization subscale was 0.82, and for the aggression subscale was 0.68. The ECIP-Q scores were negatively associated with self-esteem and prosocial behavior, and positively associated with depression symptoms and emotional and behavioral difficulties. Significant differences were found between victim and non-victim groups, and between aggressor and non-aggressor groups on the same variables. Victims and aggressors scored lower on self-esteem, and higher on depression symptoms and emotional and behavioral difficulties than those not involved in cyberbullying situations. These findings contribute to demonstrate the satisfactory psychometric quality of the ECIP-Q scores as an assessment tool for cyberbullying in Spanish adolescents.
Factors Correlated with Body Image Dissatisfaction in Children and Adolescents Diagnosed with HIV: A Cross-Sectional Study
Authors: Zanlorenci Suellem , de Souza Michele Caroline , Martins Cilene Rebolho , de Lima Luiz Rodrigo Augustemak , Silva Diego Augusto Santos
Published: October 2022

(1) Background: The adverse effects of continuous use of antiretroviral therapy can generate dissatisfaction with body image in children and adolescents diagnosed with Human Immunodeficiency Virus infection (HIV) infection. The aim of this study was to verify the prevalence and factors associated with body image dissatisfaction (BI) in children and adolescents diagnosed with HIV infection; (2) This is a cross-sectional study with 60 children and adolescents (32 females; 28 males) aged 8–15 years diagnosed with HIV, carried out in Florianópolis, Brazil. Information on BI was collected through a silhouette scale, as well as sociodemographic information, biological maturation, lifestyle, self-esteem, adherence to antiretroviral treatment and aspects of HIV infection; (3) Results: The results indicated that 53.13% of female patients and 53.57% of male patients were dissatisfied with their BI. Lower subscapular skinfold and higher calf skinfold values were associated with BI dissatisfaction in females. Pre-pubertal maturation stage, higher economic level, lower concentrations of CD4+ lymphocytes, lower viral load, lower level of physical activity and longer time in front of the computer and/or video game were associated with BI dissatisfaction in males; (4) Conclusions: BI dissatisfaction was observed in more than half of patients and morphological, economic, behavioral and HIV infection aspects were associated with BI dissatisfaction.
The Association between Peer Victimization and Risk-Taking Behavior among Chinese Adolescents: Testing a Moderated Mediation Model
Authors: Nie Yangang , Wang Guodong , Chen Pei , Wang Linxin , Dou Kai
Published: October 2022

Peer victimization has been considered a main source of risk-taking behavior among adolescents, but little is known about the mechanisms underlying this association. Based on the social–cognitive theory and the person–environment interactions model, the current study built a moderated mediation model to explore whether self-control mediated the link between peer victimization and adolescent risk-taking behavior and whether positive parenting moderated this link. We used a 2-time longitudinal design (6 months apart) to investigate 488 adolescents (Mage = 15.63 years, SD = 1.64) from 3 middle schools in Guangzhou. The results were as follows: (1) There were significant correlations among peer victimization, adolescent risk-taking behavior, self-control, and positive parenting when controlling for demographic variables. (2) Peer victimization not only influenced risk-taking behavior directly, but also indirectly through self-control. (3) Positive parenting moderated the influence of self-control on risk-taking behavior. In other words, positive parenting could enhance the inhibitory effect of self-control on risk-taking behavior. The results help reveal the mechanism by which adolescent risk-taking behavior forms and may help inform interventions against adolescent risk-taking behavior.
Distribution of Malocclusion Traits in the Pediatric Population of Milan: An Observational Study
Authors: Caccianiga Paolo , Mantovani Lorenzo Giovanni , Baldoni Marco , Caccianiga Gianluigi
Published: October 2022

Background: Epidemiological investigations define the prevalence and distribution of the various types of malocclusions, and can help to identify etiological factors and set the most correct orthodontic therapy. Aim: The goal of this study was to verify the prevalence and distribution of various types of malocclusions in the pediatric population. Methods: The study was performed on a sample of 350 patients (ages 5–9) being treated at the ASST Grande Ospedale Metropolitano Niguarda in Milan. A comparison was presented with one similar epidemiological investigation conducted 22 years earlier by the same researchers. The values of the malocclusion indices were reported from the cephalometric analyzes of the patients and were differentiated on the basis of gender and ethnicity. Results: The predominant traits of malocclusion in the general population of the analyzed sample were: skeletal class II (47.43%), hyper-divergence (40.86%), maxillary retrusion (46%), mandibular retrusion (66%), maxillary hypoplasia (50%), mandibular hypoplasia (49.14%), Wits index > 2 mm (22.57%); overjet > 4 mm (31.1%) and overbite > 4 mm (24.86%). Substantial differences were found between Italian patients and patients belonging to different ethnic groups in almost all parameters, and between the male and female genders in some of them. Patients in the 2000 study had a higher prevalence of Class II and hyper-divergence. Conclusions: This epidemiological investigation can suggest different approaches in setting the orthodontic treatment plan based on the ethnic group of the patient taken in charge and encourage more specific and large-scale analytical studies on the subject.
Analysis of Variables That Influence the Walkability of School Environments Based on the Delphi Method
Authors: Cerro-Herrero David , Prieto-Prieto Josué , Vaquero-Solis Mikel , Tapia-Serrano Miguel Ángel , Sánchez-Miguel Pedro Antonio
Published: October 2022

Walkability is determined the presence or absence of factors such as quality sidewalks, pedestrian crossings, traffic, etc. The ability to walk to the school environment may be one of the variables that promotes active commuting levels. The aim of this study was to examine the walkability of school environments using the Delphi method. This study used the Delphi method to measure the walkability. A total of 18 experts were selected. First, a list of variables was designed by the control group and sent three times to the experts. Later, the items were analyzed qualitatively and quantitatively to test the consensus of the experts. The list of variables that influence walkability showed a good consensus among the experts at the end of the process. This list was formed by 48 items and organized in six factors: traffic and safety (eleven items), signage (eight items), sidewalk (ten items), transport consistency (five items), activity (five items), and finally, urban planning (nine items). The experts agreed on the need to analyze the environments of educational centers and measure the variables that affect walkability. This study has identified the most important barriers. In the future, a measurement instrument should be developed that allows centers to be compared with others in terms of their levels of walkability. Moreover, it might be a resource for more policies to be developed with the aim to promote active commuting to school.
MRI Bone Abnormality of the Knee following Ultrasound Therapy: Case Report and Short Review
Authors: Moussadikine Ismaël , Nguyễn Mỹ-Vân , Nich Christophe , Arrigoni Pierre-Paul , Quinette Yonis , Crenn Vincent
Published: October 2022

Ultrasound (US) therapy in sports and medical pathologies is widely used by many physiotherapists and sports medicine clinicians; however, data regarding their potential side effects remain rare. We report a case of a 21-year-old woman with iliotibial band (ITB) syndrome treated with a physiotherapy session combined with US therapy. She had twenty 7 min US sessions on the knee, for 3 months (US at 1 Mhz with an intensity between 1 and 2 W/cm2). Due to persistence of the ITB syndrome’s symptomatology after the 3 months of physiotherapy sessions, an MRI (magnetic resonance imaging) was carried out and revealed osteonecrosis-like bone abnormalities on the external femoral condyle, the external tibial plateau, and the proximal fibula. In view of these lesions, the ultrasonic therapy was stopped, and a repeat MRI demonstrated the progressive disappearance of these imaging abnormalities one year after the last US (ultrasound) treatment. In light of this case, we propose here a short review of reported osseous “osteonecrosis” abnormalities associated with US therapies.
Analysis of Running Gait in Children with Cerebral Palsy: Barefoot vs. a New Ankle Foot Orthosis
Authors: Camuncoli Federica , Barbonetti Alessia , Piccinini Luigi , Di Stanislao Eugenio , Corbetta Claudio , Dell’Orto Gabriele , Bertozzi Filippo , Galli Manuela
Published: October 2022

Running is an essential activity for children with cerebral palsy (CP). This study aims to characterize the locomotor pattern of running in hemiplegic children with new generation ankle foot orthosis (AFOs) conceived to foster intense motor activities such as running. A group of 18 children with spastic hemiplegia was recruited. A biomechanical multivariable comparison was made between barefoot and with AFO running trials. The focus was devoted to bilateral sagittal plane hip, knee, ankle kinematics and kinetics, and three-dimensional ground reaction forces. Wearing the orthoses, the children were found to reduce cadence and the duration of the stance phase as well as increase the step and stride length. The new AFO resulted in significant changes in kinematics of affected ankle both at initial contact 0–3% GC (p < 0.017) and during the entire swing phase 31–100%GC (p < 0.001) being the ankle more dorsiflexed with AFO compared to barefoot condition. Ankle power was found to differ significantly both in absorption and generation 5–10%GC (p < 0.001); 21–27%GC (p < 0.001) with a reduction in both cases when the AFO was worn. No statistical differences were recorded in the GRF components, in the affected ankle torque and hip and knee kinematics and kinetics.
Compassionate Work Environments and Their Role in Teachers’ Life Satisfaction: The Contribution of Perceived Collective School Performance and Burnout
Authors: Buonomo Ilaria , Pansini Martina , Cervai Sara , Benevene Paula
Published: October 2022

Several studies on helping professionals showed the protective role of compassion among colleagues and leaders. Despite this, studies on well-being factors at school, both preventive and protective, usually focus on teachers’ personal resources and study compassion in the teacher–student relationship. This study explores the role of received compassion at work on teachers’ life satisfaction while considering perceived school collective performance and burnout conditions as mediators in this link. One hundred and eighty-six Italian teachers (female = 85.4%, mean age = 48.5, SD = 9.46) completed a questionnaire on received compassion at work, perceived school collective performance, burnout, and life satisfaction. Through a structural equation model (χ2(21) = 30.716, p = 0.08, CFI = 0.989, TLI = 0.981, RMSEA = 0.050 (90% CI = 0.000–0.080, p = 0.465), SRMR = 0.038), it emerged that only perceived school collective performance mediated the association between received compassion and life satisfaction. To the best of our knowledge, few studies have addressed the role of compassion received from colleagues and supervisors at school and its effect on teachers’ work-related beliefs and personal well-being.
Technical Analysis of Contact Tracing Platform Developed by Google–Apple for Constraining the Spread of COVID-19
Authors: Majeed Abdul
Published: October 2022

Amid the ongoing COVID-19 pandemic, technical solutions (e.g., smartphone apps, web-based platforms, digital surveillance platforms, etc.) have played a vital role in constraining the spread of COVID-19. The major aspects in which technical solutions have helped the general public (or health officials) are contact tracing, spread prediction, trend forecasting, infection risk estimation, hotspot identification, alerting people to stay away from contaminated places, hospitalization length estimation, clinical severity analysis, and quarantine monitoring, to name a few. Apart from other services, contact tracing has been extensively performed with the help of Bluetooth and GPS-powered smartphone applications when vaccines were unavailable. In this article, we technically analyze the contact tracing platform developed by Google–Apple for constraining the spread of COVID-19. We suggest unexplored technical functionalities that can further strengthen the platform from privacy preservation, service scenarios, and robustness point of view. Lastly, some AI-based and privacy-assured services that can be integrated with the platform to control the pandemic adequately are suggested. The technical analysis demonstrates that while the Google–Apple platform is well-engineered, it is not free of vulnerabilities, weaknesses, and misconfigurations that may lead to its poor adoption in real-life scenarios. This work can serve as a guideline for further enhancing the practicality of contact tracing platform to effectively handle future infectious diseases.
Thematic Content and Visualization Strategy for Map Design of City-Specific Culture Based on Local Chronicles: A Case Study of Dengfeng City, China
Authors: He Xiaohui , Liu Chuan , Wu Lili , Wang Yongji , Tian Zhihui
Published: October 2022

Local chronicles are a kind of historical record in China that are written in detail and play an important role in the transmission of local history and culture. Due to the single-text-carrier form of local chronicles, people have limited access to information on urban characteristics and culture; therefore, based on the cultural gene theory and Hofstede model, also known as the cultural onion model, this paper develops a “Spirit–Sign” content framework with the themes of urban characteristics and culture. Based on this framework, we map the urban characteristics and culture (visualization strategy and map design) of local chronicles. Taking the historic city of Dengfeng in the Central Plains as an example, the spatial information of the four historical city characteristics of Dengfeng was mined for the map design using the content framework of the city characteristics proposed in this study. The results of the study found that (1) there is a certain overlap in the spatial distribution of the four characteristic cultures of Dengfeng, indicating that the spiritual (traditional customs and famous people and events) and material (famous buildings and products) are complementary and mutually reinforcing to a certain extent; and (2) with the iterative development of Chinese dynasties, the material characteristic cultures of Dengfeng show strong temporal and spatial differences, which laterally reflect the changes in human activities and urban changes of each dynasty and also reflect the very important historical position occupied by Dengfeng in China. Compared with the traditional text-carrier form of local chronicles, the content construction and map visualization of the city’s historical and cultural information proposed in this study can effectively explore more potential cultural characteristics, as well as spatial and temporal connections of Dengfeng and thus help people better understand the historical characteristics of the city.
Spatio-Temporal Unequal Interval Correlation-Aware Self-Attention Network for Next POI Recommendation
Authors: Li Zheng , Huang Xueyuan , Liu Chun , Yang Wei
Published: October 2022

As the core of location-based social networks (LBSNs), the main task of next point-of-interest (POI) recommendation is to predict the next possible POI through the context information from users’ historical check-in trajectories. It is well known that spatial–temporal contextual information plays an important role in analyzing users check-in behaviors. Moreover, the information between POIs provides a non-trivial correlation for modeling users visiting preferences. Unfortunately, the impact of such correlation information and the spatio–temporal unequal interval information between POIs on user selection of next POI, is rarely considered. Therefore, we propose a spatio-temporal unequal interval correlation-aware self-attention network (STUIC-SAN) model for next POI recommendation. Specifically, we first use the linear regression method to obtain the spatio-temporal unequal interval correlation between any two POIs from users’ check-in sequences. Sequentially, we design a spatio-temporal unequal interval correlation-aware self-attention mechanism, which is able to comprehensively capture users’ personalized spatio-temporal unequal interval correlation preferences by incorporating multiple factors, including POIs information, spatio-temporal unequal interval correlation information between POIs, and the absolute positional information of corresponding POIs. On this basis, we perform next POI recommendation. Finally, we conduct comprehensive performance evaluation using large-scale real-world datasets from two popular location-based social networks, namely, Foursquare and Gowalla. Experimental results on two datasets indicate that the proposed STUIC-SAN outperformed the state-of-the-art next POI recommendation approaches regarding two commonly used evaluation metrics.
PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells
Authors: Greco Maria Francesca , Rizzuto Alessandra Stefania , Zarà Marta , Cafora Marco , Favero Chiara , Solazzo Giulia , Giusti Ilaria , Adorni Maria Pia , Zimetti Francesca , Dolo Vincenza , Banfi Cristina , Ferri Nicola , Sirtori Cesare R. , Corsini Alberto , Barbieri Silvia Stella , Pistocchi Anna , Bollati Valentina , Macchi Chiara , Ruscica Massimiliano
Published: October 2022

Vascular smooth muscle cells (VSMCs) are key participants in both early- and late-stage atherosclerosis and influence neighbouring cells possibly by means of bioactive molecules, some of which are packed into extracellular vesicles (EVs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed and secreted by VSMCs. This study aimed to unravel the role of PCSK9 on VSMCs-derived EVs in terms of content and functionality. EVs were isolated from human VSMCs overexpressing human PCSK9 (VSMCPCSK9-EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMCPCSK9-EVs caused a rise in the expression of adhesion molecules in endothelial cells and of pro-inflammatory cytokines in monocytes. These acquired an increased migratory capacity, a reduced oxidative phosphorylation and secreted proteins involved in immune response and immune effector processes. Concerning macrophages, VSMCPCSK9-EVs enhanced inflammatory milieu and uptake of oxidized low-density lipoproteins, whereas the migratory capacity was reduced. When injected into zebrafish embryos, VSMCPCSK9-EVs favoured the recruitment of macrophages toward the site of injection. The results of the present study provide evidence that PCSK9 plays an inflammatory role by means of EVs, at least by those derived from smooth muscle cells of vascular origin.
Bactericidal/Permeability-Increasing Protein Downregulates the Inflammatory Response in In Vivo Models of Arthritis
Authors: Scanu Anna , Luisetto Roberto , Oliviero Francesca , Galuppini Francesca , Lazzarin Vanni , Pennelli Gianmaria , Masiero Stefano , Punzi Leonardo
Published: October 2022

We investigated the effects of bactericidal/permeability-increasing protein (BPI) alone or in combination with hyaluronic acid (HA) in two animal models: collagen-induced arthritis (CIA) and crystal-induced inflammation. In CIA, mice were intraperitoneally injected with PBS, HA, or BPI plus or minus HA, twice a week for 2 months, and then euthanized to collect paw and blood. Arthritis was assessed in ankle joints by clinical and histological evaluation. Pathogenic crystals were intraperitoneally injected in mice plus or minus BPI, or with a composition of BPI and HA. After sacrifice, total and differential leukocyte counts were determined. Cytokine levels were measured in serum and peritoneal fluids. In CIA mice, BPI improved clinical and histological outcomes (histological scores ≥2-fold), and downregulated inflammatory mediators (47–93%). In crystal-induced inflammation, BPI reduced leukocyte infiltration (total count: ≥60%; polymorphonuclear cells: ≥36%) and inhibited cytokine production (35–74%). In both models, when mice were co-treated with BPI and HA, the improvement of all parameters was greater than that observed after administration of the two substances alone. Results show that BPI attenuates CIA and inflammation in mice, and this effect is enhanced by HA co-administration. Combined use of BPI and HA represents an interesting perspective for new potential treatments in arthritis.
The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas
Authors: Li Zhenye , Chen Yiyuan , Yao Xiaohui , Liu Qian , Zhu Haibo , Zhang Yazhuo , Feng Jie , Gao Hua
Published: October 2022

Somatotroph adenomas are the leading cause of acromegaly, with the nearly sparsely granulated somatotroph subtype belonging to high-risk adenomas, and they are less responsive to medical treatment. The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. In this study, we identified the characteristic profiling of the integrated stress response in translocation and translation initiation factor activity in somatotroph adenomas, normal pituitary, or other adenoma subtypes through proteomics. Immunohistochemistry exhibited the differential significance and the priority of eukaryotic translation initiation factor 2β (EIF2β) in somatotroph adenomas compared with gonadotroph and corticotroph adenomas. Differentially expressed genes based on the level of EIF2β in somatotroph adenomas were revealed. MetaSape pathways showed that EIF2β was involved in regulating growth and cell activation, immune system, and extracellular matrix organization processes. The correlation analysis showed Spearman correlation coefficients of r = 0.611 (p < 0.001) for EIF2β and eukaryotic translation initiation factor 2 alpha kinase 1 (HRI), r = 0.765 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 2 (PKR), r = 0.813 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 3 (PERK), r = 0.728 (p < 0.001) for GCN2, and r = 0.732 (p < 0.001) for signal transducer and activator of transcription 3 (STAT3). Furthermore, the invasive potential in patients with a high EIF2β was greater than that in patients with a low EIF2β (7/10 vs. 4/18, p = 0.038), with a lower immune-cell infiltration probability (p < 0.05). The ESTIMATE algorithm showed that the levels of activation of the EIF2 pathway were negatively correlated with the immune score in somatotroph adenomas (p < 0.001). In in vitro experiments, the knockdown of EIF2β changed the phenotype of somatotroph adenomas, including cell proliferation, migration, and the secretion ability of growth hormone/insulin-like growth factor-1. In this study, we demonstrate that the ISR is pivotal in somatotroph adenomas and provide a rationale for implementing ISR-based regimens in future treatment strategies.
Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii
Authors: Lin Tzu-Lung , Lu Cha-Chen , Chen Ting-Wen , Huang Chih-Wei , Lu Jang-Jih , Lai Wei-Fan , Wu Ting-Shu , Lai Chih-Ho , Lai Hsin-Chih , Chen Ya-Lei
Published: October 2022

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.
Skin Barrier Function and the Microbiome
Authors: Lee Hyun-Ji , Kim Miri
Published: October 2022

Human skin is the largest organ and serves as the first line of defense against environmental factors. The human microbiota is defined as the total microbial community that coexists in the human body, while the microbiome refers to the collective genome of these microorganisms. Skin microbes do not simply reside on the skin but interact with the skin in a variety of ways, significantly affecting the skin barrier function. Here, we discuss recent insights into the symbiotic relationships between the microbiome and the skin barrier in physical, chemical, and innate/adaptive immunological ways. We discuss the gut-skin axis that affects skin barrier function. Finally, we examine the effects of microbiome dysbiosis on skin barrier function and the role of these effects in inflammatory skin diseases, such as acne, atopic dermatitis, and psoriasis. Microbiome cosmetics can help restore skin barrier function and improve these diseases.
FtbZIP12 Positively Regulates Responses to Osmotic Stress in Tartary Buckwheat
Authors: Weng Wenfeng , Lu Xiang , Zhou Meiliang , Gao Anjing , Yao Xin , Tang Yong , Wu Weijiao , Ma Chao , Bai Qing , Xiong Ruiqi , Ruan Jingjun
Published: October 2022

ABFs play a key role in regulating plant osmotic stress. However, in Tartary buckwheat, data on the role of ABF genes in osmotic stress remain limited and its associated mechanism in osmoregulation remain nebulous. Herein, a novel ABF family in Tartary buckwheat, FtbZIP12, was cloned and characterized. FtbZIP12 is a transcriptional activator located in the nucleus; its expression is induced by NaCl, mannitol, and abscisic acid (ABA). Atopic expression of FtbZIP12 in Arabidopsis promoted seed germination, reduced damage to primary roots, and improved the tolerance of seedlings to osmotic stress. The quantitative realtime polymerase chain reaction (RT-qPCR) results showed that the expressions of the typical genes related to stress, the SOS pathway, and the proline synthesis pathway in Arabidopsis were significantly (p < 0.05) upregulated under osmotic stress. FtbZIP12 improved the osmotic pressure resistance by reducing the damage caused by reactive oxygen species to plants and maintained plant homeostasis by upregulating the expression of genes related to stress, osmotic regulation, and ion homeostasis. This study identified a key candidate gene for understanding the mechanism underlying osmotic-stress-regulated function in Tartary buckwheat, thereby providing a theoretical basis for improving its yield and quality.
Apelin-13 Increases Functional Connexin-43 through Autophagy Inhibition via AKT/mTOR Pathway in the Non-Myocytic Cell Population of the Heart
Authors: Vitale Emanuela , Rosso Rachele , Lo Iacono Marco , Cristallini Caterina , Giachino Claudia , Rastaldo Raffaella
Published: October 2022

Studies have shown a link between the downregulation of connexin 43 (Cx43), the predominant isoform in cardiac gap junctions, and high susceptibility to cardiac arrhythmias and cardiomyocyte death. Non-myocytic cells (NMCs), the most abundant component of the heart, exert multiple cardiac functions and represent an important therapeutic target for diseased cardiac tissue. A few studies have investigated the effect of Apelin-13, an endogenous peptide with a key role in various cardiovascular functions, on Cx43 expression in cardiomyocytes. However, it remained unknown whether Apelin-13 influences Cx43 expression in NMCs. Here, we found that in NMCs, Cx43 protein expression increased after Apelin-13 treatment (100 nM for 48 h). Furthermore, dye transfer assays proved that Apelin-13-treated NMCs had a greater ability to communicate with surrounding cardiomyocytes, and this effect was abrogated by carbenoxolone, a gap junction inhibitor. Interestingly, we showed that Apelin-13 increased Cx43 through autophagy inhibition, as proved by the upregulation of p62 and LC3I, acting as 3-MA, a well-known autophagy inhibitor. In addition, Apelin-13-induced AKT and mTOR phosphorylation was abolished by LY294002 and rapamycin inhibitors resulting in Cx43 increased suppression. These results open the possibility of targeting gap junctions in NMCs with Apelin-13 as an exciting therapeutic approach with great potential.
Allosteric Modulation of Muscarinic Receptors by Cholesterol, Neurosteroids and Neuroactive Steroids
Authors: Szczurowska Ewa , Szánti-Pintér Eszter , Randáková Alena , Jakubík Jan , Kudova Eva
Published: October 2022

Muscarinic acetylcholine receptors are membrane receptors involved in many physiological processes. Malfunction of muscarinic signaling is a cause of various internal diseases, as well as psychiatric and neurologic conditions. Cholesterol, neurosteroids, neuroactive steroids, and steroid hormones are molecules of steroid origin that, besides having well-known genomic effects, also modulate membrane proteins including muscarinic acetylcholine receptors. Here, we review current knowledge on the allosteric modulation of muscarinic receptors by these steroids. We give a perspective on the research on the non-genomic effects of steroidal compounds on muscarinic receptors and drug development, with an aim to ultimately exploit such knowledge.
An Ultra-Rare Manifestation of an X-Linked Recessive Disorder: Duchenne Muscular Dystrophy in a Female Patient
Authors: Szűcs Zsuzsanna , Pinti Éva , Haltrich Irén , Szén Orsolya Pálné , Nagy Tibor , Barta Endre , Méhes Gábor , Bidiga László , Török Olga , Ujfalusi Anikó , Koczok Katalin , Balogh István
Published: October 2022

Duchenne muscular dystrophy (DMD) is the most common inherited muscle dystrophy. Patients are characterized by muscle weakness, gross motor delay, and elevated serum creatinine kinase (CK) levels. The disease is caused by mutations in the DMD gene located on the X chromosome. Due to the X-linked recessive inheritance pattern, DMD most commonly affects males, who are generally diagnosed between the age of 3–5 years. Here we present an ultra-rare manifestation of DMD in a female patient. Cytogenetic examination showed that she has a t(X;10)(p21.1;p12.1) translocation, which turned out to affect the DMD gene with one of the breakpoints located in exon 54 (detected by genome sequencing). The X-inactivation test revealed skewed X-inactivation (ratio 99:1). Muscle histology and dystrophin immunohistochemistry showed severe dystrophic changes and highly reduced dystrophin expression, respectively. These results, in accordance with the clinical picture and a highly elevated serum CK, led to the diagnosis of DMD. In conclusion, although in very rare cases, DMD can manifest in female patients as well. In this case, a balanced X-autosome reciprocal translocation disrupts the DMD gene and skewed X-inactivation leads to the manifestation of the DMD phenotype.
Genome-Wide Identification of Strawberry C2H2-ZFP C1-2i Subclass and the Potential Function of FaZAT10 in Abiotic Stress
Authors: Li Hao , Yue Maolan , Jiang Leiyu , Liu Yongqiang , Zhang Nating , Liu Xiaoling , Ye Yuyun , Lin Ximeng , Zhang Yunting , Lin Yuanxiu , Li Mengyao , Wang Yan , Zhang Yong , Luo Ya , Wang Xiaorong , Chen Qing , Tang Haoru
Published: October 2022

C2H2-type zinc finger proteins (C2H2-ZFPs) play a key role in various plant biological processes and responses to environmental stresses. In Arabidopsisthaliana, C2H2-ZFP members with two zinc finger domains have been well-characterized in response to abiotic stresses. To date, the functions of these genes in strawberries are still uncharacterized. Here, 126 C2H2-ZFPs in cultivated strawberry were firstly identified using the recently sequenced Fragaria × ananassa genome. Among these C2H2-ZFPs, 46 members containing two zinc finger domains in cultivated strawberry were further identified as the C1-2i subclass. These genes were unevenly distributed on 21 chromosomes and classified into five groups according to the phylogenetic relationship, with similar physicochemical properties and motif compositions in the same group. Analyses of conserved domains and gene structures indicated the evolutionary conservation of the C1-2i subclass. A Ka/Ks analysis indicated that the C1-2i members were subjected to purifying selection during evolution. Furthermore, FaZAT10, a typical C2H2-ZFP, was isolated. FaZAT10 was expressed the highest in roots, and it was induced by drought, salt, low-temperature, ABA, and MeJA treatments. It was localized in the nucleus and showed no transactivation activity in yeast cells. Overall, these results provide useful information for enriching the analysis of the ZFPs gene family in strawberry, and they provide support for revealing the mechanism of FaZAT10 in the regulatory network of abiotic stress.
Depleted Calcium Stores and Increased Calcium Entry in Rod Photoreceptors of the Cacna2d4 Mouse Model of Cone-Rod Dystrophy RCD4
Authors: Vellani Vittorio , Mauro Giovanna , Demontis Gian Carlo
Published: October 2022

Unidentified pathogenetic mechanisms and genetic and clinical heterogeneity represent critical factors hindering the development of treatments for inherited retinal dystrophies. Frameshift mutations in Cacna2d4, which codes for an accessory subunit of voltage-gated calcium channels (VGCC), cause cone-rod dystrophy RCD4 in patients, but the underlying mechanisms remain unknown. To define its pathogenetic mechanisms, we investigated the impact of a Cacna2d4 frameshift mutation on the electrophysiological profile and calcium handling of mouse rod photoreceptors by patch-clamp recordings and calcium imaging, respectively. In mutant (MUT) rods, the dysregulation of calcium handling extends beyond the reduction in calcium entry through VGCC and surprisingly involves internal calcium stores’ depletion and upregulation of calcium entry via non-selective cationic channels (CSC). The similar dependence of CSC on basal calcium levels in WT and MUT rods suggests that the primary defect in MUT rods lies in defective calcium stores. Calcium stores’ depletion, leading to upregulated calcium and sodium influx via CSC, represents a novel and, so far, unsuspected consequence of the Cacna2d4 mutation. Blocking CSC may provide a novel strategy to counteract the well-known pathogenetic mechanisms involved in rod demise, such as the reticulum stress response and calcium and sodium overload due to store depletion.
PsnWRKY70 Negatively Regulates NaHCO3 Tolerance in Populus
Authors: Wang Wei , Bai Xiang-Dong , Chen Kun , Zhang Xiao-Yue , Gu Chen-Rui , Jiang Jing , Yang Chuan-Ping , Liu Gui-Feng
Published: October 2022

Poplar is an important afforestation and ornamental tree species in Northeast China. The distribution area of saline-alkali land is approximately 765 hm2 in Northeast China. The breeding of saline-alkali-resistant transgenic trees could be an effective method of afforestation in saline-alkali land. WRKY transcription factors play a crucial role in abiotic stress. In this study, we analyzed the genetic stability of the two-year-old PsnWRKY70 transgenic poplars. The results showed that PsnWRKY70 of transgenic poplars had been expressed stably and normally at the mRNA level. The gene interference expression (RE) lines had no significant effect on the growth of PsnWRKY70 under NaHCO3 stress, and the alkali damage index of RE lines was significantly lower than that of WT and overexpression (OE) lines at day 15 under NaHCO3 stress. POD activity was significantly higher in RE lines than in WT. The MDA content of the RE line was lower than that of the WT line. Transcriptome analysis showed that RE lines up-regulated genes enriched in cell wall organization or biogenesis pathway-related genes such as EXPA8, EXPA4, EXPA3, EXPA1, EXPB3, EXP10, PME53, PME34, PME36, XTH9, XTH6, XTH23, CESA1, CESA3, CES9; FLA11, FLA16 and FLA7 genes. These genes play an important role in NaHCO3 stress. Our study showed that the interference expression of the PsnWRKY70 gene can enhance the tolerance of NaHCO3 in poplar.
Availability of Ferritin-Bound Iron to Enterobacteriaceae
Authors: Gehrer Clemens M. , Hoffmann Alexander , Hilbe Richard , Grubwieser Philipp , Mitterstiller Anna-Maria , Talasz Heribert , Fang Ferric C. , Meyron-Holtz Esther G. , Atkinson Sarah H. , Weiss Günter , Nairz Manfred
Published: October 2022

The sequestration of iron in case of infection, termed nutritional immunity, is an established strategy of host defense. However, the interaction between pathogens and the mammalian iron storage protein ferritin is hitherto not completely understood. To better characterize the function of ferritin in Gram-negative infections, we incubated iron-starved cultures of Salmonella Typhimurium and knockout mutant strains defective for major iron uptake pathways or Escherichia coli with horse spleen ferritin or ionic iron as the sole iron source. Additionally, we added bovine superoxide dismutase and protease inhibitors to the growth medium to assess the effect of superoxide and bacterial proteases, respectively, on Salmonella proliferation and reductive iron release. Compared to free ionic iron, ferritin-bound iron was less available to Salmonella, but was still sufficient to significantly enhance the growth of the bacteria. In the absence of various iron acquisition genes, the availability of ferritin iron further decreased. Supplementation with superoxide dismutase significantly reduced the growth of the ΔentC knockout strain with holoferritin as the sole iron source in comparison with ionic ferrous iron. In contrast, this difference was not observed in the wildtype strain, suggesting that superoxide dismutase undermines bacterial iron uptake from ferritin by siderophore-independent mechanisms. Ferritin seems to diminish iron availability for bacteria in comparison to ionic iron, and its iron sequestering effect could possibly be enhanced by host superoxide dismutase activity.
Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
Authors: Cavalu Simona , Elbaramawi Samar S. , Eissa Ahmed G. , Radwan Mohamed F. , S. Ibrahim Tarek , Khafagy El-Sayed , Lopes Bruno Silvester , Ali Mohamed A. M. , Hegazy Wael A. H. , Elfaky Mahmoud A.
Published: October 2022

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two β-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the β-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.
The Role of Connexin 43 in Renal Disease: Insights from In Vivo Models of Experimental Nephropathy
Authors: Roger Elena , Boutin Louis , Chadjichristos Christos E.
Published: October 2022

Renal disease is a major public health challenge since its prevalence has continuously increased over the last decades. At the end stage, extrarenal replacement therapy and transplantation remain the only treatments currently available. To understand how the disease progresses, further knowledge of its pathophysiology is needed. For this purpose, experimental models, using mainly rodents, have been developed to unravel the mechanisms involved in the initiation and progression of renal disease, as well as to identify potential targets for therapy. The gap junction protein connexin 43 has recently been identified as a novel player in the development of kidney disease. Its expression has been found to be altered in many types of human renal pathologies, as well as in different animal models, contributing to the activation of inflammatory and fibrotic processes that lead to renal damage. Furthermore, Cx43 genetic, pharmacogenetic, or pharmacological inhibition preserved renal function and structure. This review summarizes the existing advances on the role of this protein in renal diseases, based mainly on different in vivo animal models of acute and chronic renal diseases.
Biological Cover Mitigates Disruption of the Dermal Structure in Mechanically Expanded Skin in a Porcine Model
Authors: Ledwon Joanna K. , Applebaum Sarah A. , Progri Bianka , Vignesh Oveyaa , Gutowski Kristof S. , Chang Alec B. , Tepole Adrian B. , Gosain Arun K.
Published: October 2022

Tissue expansion is an integral procedure of the vast majority of breast reconstruction and has a significant impact on the final clinical outcomes. Therefore, technological advances leading to a fewer number of unfavorable outcomes and a decrease in complication rates are imperative. In this study, using a porcine model, we investigated an effect of acellular dermal matrix (ADM) used as a tissue expander cover on the dermal changes induced by mechanical forces during tissue expansion. After 14 days of expansion, skin samples were collected from one animal, while the second animal underwent radiation, and tissue was collected 8 weeks later. Tissue expanded without the use of ADM and unexpanded skin served as the controls. Collected skin biopsies were used for histological and immunohistochemical evaluation, and for gene expression analysis. We revealed that the biological cover incorporation into host tissue is facilitated by macrophages without inducing a broad inflammatory response. The utilization of ADM mitigated disruption in the dermal structure, excessive collagen deposition, and capsule formation in non-irradiated expanded skin. The protective effect was not fully maintained in irradiated skin. These results demonstrate that tissue expansion might be improved by using the tissue expander cover.