bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Balance and Postural Control According to the Stabilometry in Indoor Skydivers: A Cross-Sectional Study
Authors: López-de-Celis Carlos , Zegarra-Chávez Daniel , Cadellans-Arróniz Aïda , Carrasco-Uribarren Andoni , Izquierdo-Nebreda Pedro , Canet-Vintró Max , Rodríguez-Sanz Jacobo , Pérez-Bellmunt Albert
Published: December 2022

Background: The wind tunnel is a compression cabin through which a stream of air rises homogeneously, generated by fans. To perform different acrobatics, indoor skydivers have to change their body position by turning their body and orientation in reference to the space. Thus, the vestibular, visual and somatosensory systems are subjected to multiple disturbances. Postural control could be affected by altering the visual, vestibular and somatosensory systems during indoor skydiving in the wind tunnel. The aim of this study is to describe the influence of a standard wind tunnel training session on postural control in a normal gravitational situation in indoor skydiving. Methods: Ten indoor skydivers registered with the Royal Spanish Aeronautical Federation, who had participated in national or international competitions one year ago, were recruited. A single 30 min training session was performed. Postural control was assessed through posturographic analysis using a stabilometric platform immediately before and after the training session. The variables studied were related to the relative position and length of the centre of pressure. Results: No statistically significant changes were found between the initial and final assessment for the posturographic variables studied. Conclusions: No differences in postural control were found after a standard wind tunnel training session in indoor competition skydivers.
Evaluation of Medical Staff Satisfaction for Workplace Architecture in Temporary COVID-19 Hospital: A Case Study in Gdańsk, Poland
Authors: Gebczynska-Janowicz Agnieszka , Janowicz Rafal , Targowski Wojciech , Cudnik Rafal , Paszko Krystyna , Zielinska-Dabkowska Karolina M.
Published: December 2022

This article analyses the architecture that was used in the temporary AmberExpo hospital in Gdańsk, Poland which was installed during the COVID-19 pandemic. The construction of this type of facility is often based on experimental approaches, aimed at caring for patients suffering from an infectious disease in emergency conditions. In order to assess the level of employee satisfaction with the architectural and technical elements used in the first period of the hospital’s activity, medical staff were asked to fill out a questionnaire. The analysis of the survey’s results indicated that the majority of employees expressed satisfaction with the architectural and technical elements, with the design of the spatial layout of the individual medical zones receiving the most positive feedback. However, frequently selected drawbacks in the design included the lack of natural daylight, the artificial light that was used and the acoustics of the facility. This detailed examination of the satisfaction and feedback from medical employees working in this type of emergency facility enables the development of solutions that in the future will allow for the improved adaptive reuse and implementation of such structures, with enhanced time and economic efficiency, and most importantly, the ability to provide a safer workplace.
Empowerment-Based Physical Activity Intervention for People with Advanced Dry Age-Related Macular Degeneration: Mixed-Methods Protocol
Authors: Lindgren Eva-Carin , Källstrand Jeanette , Alftberg Åsa , Johansson Pia , Kristén Lars , Håman Linn , Ivarsson Andreas , Carlsson Ing-Marie
Published: December 2022

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment and impacts daily life. These impacts include loss of social activities, decreased functional independence, and reduced physical activity. This protocol aims to describe a prospective, mixed-methodology for studying a population with AMD before, during, and after an empowerment-based physical activity intervention (EPI). A study framework was also developed for EPI. The intervention will include 20 older individuals (age 65+ years) with AMD recruited in Sweden. The intervention period is six months and comprises adapted physical activity and social activities in a group twice a week and individual health coaching on three occasions. The quantitative pre-test and three follow-ups include physical functional tests, an accelerometer that monitors physical activity continuously for one week, and questionnaires. Individual and focus-group interviews and ethnographic observations will explore the experience of living with AMD and what it means to participate in the EPI for individuals with AMD. The chosen methodology offers a structured way for researchers to explore the experiences and factors that may provide insights into the potential of creative supervised, adapted physical activity in groups, health coaching, and socialising that are significant to enable well-being among older individuals with AMD.
Teach Me Fishing or Give Me the Fish: Differential Effects of Receiving Autonomous and Dependent Help on Task Performance
Authors: Tan Beijing , Li Ziyi , Cheng Huan , Wang Zijing
Published: December 2022

Research on workplace helping behavior highlights the need for a more balanced perspective that acknowledges both the positive and negative consequences of receiving help. The purpose of this study is to investigate how the mechanisms through which we receive autonomous and dependent help differentially impact recipient task performance, as well as the boundary condition for such effects. Drawing on social information theory, we examined the mediating role of task- and self-focused processes, and the moderating role of perceived prosocial motivation. Through a two-wave and two-source field survey, we collected matched data from 350 employees and their direct supervisors. We examined our hypothesized model with path analysis using Mplus 7.4. Results indicated that receiving autonomous help improved task performance by leading recipients into task-focused processes, and perceived prosocial motivation further strengthened this positive indirect relationship. In contrast, receiving dependent help reduced task performance by eliciting recipients to engage in self-focused processes, and perceived prosocial motivation further augmented this negative indirect relationship. Overall, we spotlight the differential consequences of receiving autonomous and dependent help on recipients and encourage further inquiry about the role of social information processing in the helping literature.
Spatiotemporal Characteristics of Coupling and Coordination of Cultural Tourism and Objective Well-Being in Western China
Authors: Pu Lili , Chen Xingpeng , Jiang Li , Zhang Hang
Published: December 2022

A supply of high-quality cultural tourism products effectively promotes people’s happiness. This study takes the coupling and coordination relationship between cultural tourism (CT) and objective well-being (OWB) in western China as the research object and constructs an index evaluation system for the development levels of cultural tourism and objective welfare, which are divided into three development stages of dysfunctional, transitional, and coordinated development and 10 coordination levels, including high-quality coordination. The entropy weight method, coupled coordination model, Thiel index, standard deviation, and coefficient of variation were used to calculate the comprehensive development index and coupling coordination degree of the CT and OWB systems in western China from 2007 to 2020, and then their evolution characteristics were analyzed from the perspectives of time and space. The results show the following: (1) The comprehensive development capacity of the CT and OWB systems in the western region shows a relatively consistent growth trend except for 2020, the overall development capacity of objective welfare was relatively high, and the development capacity of cultural tourism was relatively low. (2) The CT and OWB systems were in a state of transition from high coupling and low coordination to high coupling and high coordination, which were divided into three development stages: imbalanced stage (2007–2008), transitional stage (2009–2011), and coordinated development (2012–2020). The coordination degree has developed steadily from moderate misalignment to good coordination over time, and the diversified characteristics of coupling coordination levels are obvious. (3) The spatial equilibrium of the CT and OWB systems is obvious, and the spatial difference in the western region is getting smaller, but the relative gap is widening significantly. (4) The comprehensive development capacity of the cultural tourism system should be enhanced, the spiritual needs of residents based on objective well-being should be met, and the sustainable development of the CT and OWB systems.
Early Identification of Social, Emotional, and Behavioral Difficulties by School Staff: A Qualitative Examination of Dutch Primary School Practices
Authors: Jaspers-van der Maten Marloes L. , Rommes Els W. M. , Scholte Ron H. J.
Published: December 2022

About 16% of Dutch children are reported to have social, emotional, and behavioral difficulties (SEBDs). SEBDs generate distress and pose risks for various negative outcomes; thus, their timely identification is deemed important to respond appropriately to children’s needs and avoid such negative outcomes. Primary schools are considered convenient places to implement early SEBD identification, but the ways in which schools achieve this in practice may be inadequate, although the issue remains under-researched. Although there are several systematic school-based early identification methods (e.g., universal or selective screening), primary schools predominantly rely on school staff to recognize children at risk for, or experiencing, SEBDs. As differences in identification practices could impact whether and when (signs of) SEBDs are identified, this study aimed to increase our understanding of differences in identification practices used by school staff and their potential implications for early identification effectiveness. Thirty-four educational and clinical professionals working at nine primary schools participated in in-depth semi-structured interviews. We used MAXQDA to thematically code and analyze the data. Our analysis of these interviews illustrated that schools’ identification practices differed on three elements: the frequency of observations, maintaining a four-eyes principle, and the utilization of specialist knowledge. We argue that differences in these elements have potential consequences for the timeliness and quality of SEBD identification.
Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review
Authors: Klein Jean-Philippe , Mery Lionel , Boudard Delphine , Ravel Célia , Cottier Michèle , Bitounis Dimitrios
Published: December 2022

The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood–testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility.
Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR)
Authors: Botrus Gehan , Miller Richard M. , Uson Junior Pedro Luiz Serrano , Kannan Geoffrey , Han Haiyong , Von Hoff Daniel D.
Published: December 2022

High rates of cell proliferation and protein synthesis in pancreatic cancer are among many factors leading to endoplasmic reticulum (ER) stress. To restore cellular homeostasis, the unfolded protein response (UPR) activates as an adaptive mechanism through either the IRE1α, PERK, or ATF6 pathways to reduce the translational load and process unfolded proteins, thus enabling tumor cells to proliferate. Under severe and prolonged ER stress, however, the UPR may promote adaptation, senescence, or apoptosis under these same pathways if homeostasis is not restored. In this review, we present evidence that high levels of ER stress and UPR activation are present in pancreatic cancer. We detail the mechanisms by which compounds activate one or many of the three arms of the UPR and effectuate downstream apoptosis and examine available data on the pre-clinical and clinical-phase ER stress inducers with the potential for anti-tumor efficacy in pancreatic cancer. Finally, we hypothesize a potential new approach to targeting pancreatic cancer by increasing levels of ER stress and UPR activation to incite apoptotic cell death.
Complex of Proline-Specific Peptidases in the Genome and Gut Transcriptomes of Tenebrionidae Insects and Their Role in Gliadin Hydrolysis
Authors: Tereshchenkova Valeriia F. , Filippova Irina Y. , Goptar Irina A. , Dunaevsky Yakov E. , Belozersky Mikhail A. , Elpidina Elena N.
Published: December 2022

A detailed analysis of the complexes of proline-specific peptidases (PSPs) in the midgut transcriptomes of the larvae of agricultural pests Tenebrio molitor and Tribolium castaneum and in the genome of T. castaneum is presented. Analysis of the T. castaneum genome revealed 13 PSP sequences from the clans of serine and metal-dependent peptidases, of which 11 sequences were also found in the gut transcriptomes of both tenebrionid species’ larvae. Studies of the localization of PSPs, evaluation of the expression level of their genes in gut transcriptomes, and prediction of the presence of signal peptides determining secretory pathways made it possible to propose a set of peptidases that can directly participate in the hydrolysis of food proteins in the larvae guts. The discovered digestive PSPs of tenebrionids in combination with the post-glutamine cleaving cysteine cathepsins of these insects effectively hydrolyzed gliadins, which are the natural food substrates of the studied pests. Based on the data obtained, a hypothetical scheme for the complete hydrolysis of immunogenic gliadin peptides by T. molitor and T. castaneum digestive peptidases was proposed. These results show promise regarding the development of a drug based on tenebrionid digestive enzymes for the enzymatic therapy of celiac disease and gluten intolerance.
Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis
Authors: Ghayee Hans K. , Xu Yiling , Hatch Heather , Brockway Richard , Multani Asha S. , Gu Tongjun , Bollag Wendy B. , Turcu Adina , Rainey William E. , Rege Juilee , Nanba Kazutaka , Bhagwandin Vikash J. , Nwariaku Fiemu , Stastny Victor , Gazdar Adi F. , Shay Jerry W. , Auchus Richard J. , Tevosian Sergei G.
Published: December 2022

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient’s macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.
Metformin Attenuates Hyperglycaemia-Stimulated Pro-Fibrotic Gene Expression in Adventitial Fibroblasts via Inhibition of Discoidin Domain Receptor 2
Authors: Titus Allen Sam , Ushakumary Mereena George , Venugopal Harikrishnan , Wang Mingyi , Lakatta Edward G. , Kailasam Shivakumar
Published: December 2022

Molecular mechanisms underlying the diverse therapeutic effects of anti-diabetic metformin, beyond its anti-hyperglycaemic effects, remain largely unclear. Metformin is reported to reduce the long-term complications of diabetes, including cardiovascular fibrosis and remodelling. Our recent investigations show that Discoidin Domain Receptor 2 (DDR2), a Collagen receptor tyrosine kinase, has an obligate regulatory role in Collagen type I gene expression in cardiac and vascular adventitial fibroblasts, and that it may be a molecular link between arterial fibrosis and metabolic syndrome in rhesus monkeys. Using gene knockdown and overexpression approaches, the present study examined whether DDR2 is a target of metformin and whether, by targeting DDR2, it inhibits Fibronectin and Collagen type I expression in rat aortic adventitial fibroblasts exposed to hyperglycaemic conditions. Metformin was found to attenuate hyperglycaemia-induced increase in DDR2 mRNA and protein expression by inhibiting TGF-β1/SMAD2/3 signalling that mediates the stimulatory effect of hyperglycaemia on DDR2 expression. Metformin also inhibited DDR2-dependent expression of Fibronectin and Collagen type I, indicating that it regulates these matrix proteins via DDR2 inhibition. The findings identify DDR2, a mediator of cardiovascular remodelling, as a molecular target of metformin, thereby uncovering the molecular basis of its protective role in vascular fibrosis and possibly cardiac fibrosis associated with diabetic cardiomyopathy.
RNA-Binding Protein MEX3A Interacting with DVL3 Stabilizes Wnt/β-Catenin Signaling in Endometrial Carcinoma
Authors: Yang Pusheng , Zhang Panpan , Zhang Shu
Published: December 2022

Disease recurrence and metastasis lead to poor prognosis in patients with advanced endometrial carcinoma (EC). RNA-binding proteins (RBPs) are closely associated with tumor initiation and metastasis, but the function and molecular mechanisms of RBPs in EC are unclear. RBPs were screened and identified using the TCGA, GEO, and RBPTD databases. The effect of MEX3A on EC was verified by in vitro and in vivo experiments. Gene set enrichment analysis (GSEA), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) were used to identify potential molecular mechanisms of action. We identified 148 differentially expressed RBPs in EC. MEX3A was upregulated and related to poor prognosis in patients with EC. In vitro and vivo experiments demonstrated that MEX3A promoted the growth, migration, and invasion capacities of EC cells. Mechanistically, DVL3, a positive regulator of the Wnt/β-catenin pathway, also increased the proliferation and metastasis of EC cells. MEX3A enhanced EMT and played a pro-carcinogenic role by interacting with DVL3 to stabilize β-catenin and upregulated the expression of its downstream target genes. MEX3A is upregulated in EC and promotes tumor progression by activating EMT and regulating the Wnt/β-catenin pathway via DVL3. MEX3A may therefore be a novel therapeutic target for EC.
Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells
Authors: Pivarcsik Tamás , Pósa Vivien , Kovács Hilda , May Nóra V. , Spengler Gabriella , Pósa Szonja P. , Tóth Szilárd , Nezafat Yazdi Zeinab , Özvegy-Laczka Csilla , Ugrai Imre , Szatmári István , Szakács Gergely , Enyedy Éva A.
Published: December 2022

Multidrug resistance (MDR) in cancer is one of the major obstacles of chemotherapy. We have recently identified a series of 8-hydroxyquinoline Mannich base derivatives with MDR-selective toxicity, however with limited solubility. In this work, a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(η5-C5Me5) and Ru(η6-p-cymene) complexes with excellent aqueous solubility were developed, characterized, and tested against sensitive and MDR cells. Complex formation of the ligand with essential metal ions was also investigated using UV-visible, circular dichroism, 1H NMR (Zn(II)), and electron paramagnetic resonance (Cu(II)) spectroscopic methods. Formation of mono and bis complexes was found in all cases with versatile coordination modes, while tris complexes were also formed with Fe(II) and Fe(III) ions, revealing the metal binding affinity of the ligand at pH 7.4: Cu(II) > Zn(II) > Fe(II) > Fe(III). The ligand and its Rh(III) complex displayed enhanced cytotoxicity against the resistant MES-SA/Dx5 and Colo320 human cancer cell lines compared to their chemosensitive counterparts. Both organometallic complexes possess high stability in solution, however the Ru(II) complex has lower chloride ion affinity and slower ligand exchange processes, along with the readiness to lose the arene ring that is likely connected to its inactivity.
HMGA1 Regulates the Expression of Replication-Dependent Histone Genes and Cell-Cycle in Breast Cancer Cells
Authors: Petrosino Sara , Pacor Sabrina , Pegoraro Silvia , Gazziero Virginia Anna , Canarutto Giulia , Piazza Silvano , Manfioletti Guidalberto , Sgarra Riccardo
Published: December 2022

Breast cancer (BC) is the primary cause of cancer mortality in women and the triple-negative breast cancer (TNBC) is the most aggressive subtype characterized by poor differentiation and high proliferative properties. High mobility group A1 (HMGA1) is an oncogenic factor involved in the onset and progression of the neoplastic transformation in BC. Here, we unraveled that the replication-dependent-histone (RD-HIST) gene expression is enriched in BC tissues and correlates with HMGA1 expression. We explored the role of HMGA1 in modulating the RD-HIST genes expression in TNBC cells and show that MDA-MB-231 cells, depleted of HMGA1, express low levels of core histones. We show that HMGA1 participates in the activation of the HIST1H4H promoter and that it interacts with the nuclear protein of the ataxia-telangiectasia mutated locus (NPAT), the coordinator of the transcription of the RD-HIST genes. Moreover, we demonstrate that HMGA1 silencing increases the percentage of cells in G0/G1 phase both in TNBC and epirubicin resistant TNBC cells. Moreover, HMGA1 silencing causes an increase in epirubicin IC50 both in parental and epirubicin resistant cells thus suggesting that targeting HMGA1 could affect the efficacy of epirubicin treatment.
Biofilm Formation by Staphylococcus aureus in the Specific Context of Cystic Fibrosis
Authors: Jean-Pierre Vincent , Boudet Agathe , Sorlin Pauline , Menetrey Quentin , Chiron Raphaël , Lavigne Jean-Philippe , Marchandin Hélène
Published: December 2022

Staphylococcus aureus is a major human pathogen whose characteristics support its success in various clinical settings including Cystic Fibrosis (CF). In CF, S. aureus is indeed the most commonly identified opportunistic pathogen in children and the overall population. S. aureus colonization/infection, either by methicillin-susceptible or methicillin-resistant strains, will become chronic in about one third of CF patients. The persistence of S. aureus in CF patients’ lungs, despite various eradication strategies, is favored by several traits in both host and pathogen. Among the latter, living in biofilm is a highly protective way to survive despite deleterious environmental conditions, and is a common characteristic shared by the main pathogens identified in CF. This is why CF has earned the status of a biofilm-associated disease for several years now. Biofilm formation by S. aureus, and the molecular mechanisms governing and regulating it, have been extensively studied but have received less attention in the specific context of CF lungs. Here, we review the current knowledge on S. aureus biofilm in this very context, i.e., the importance, study methods, molecular data published on mono- and multi-species biofilm and anti-biofilm strategies. This focus on studies including clinical isolates from CF patients shows that they are still under-represented in the literature compared with studies based on reference strains, and underlines the need for such studies. Indeed, CF clinical strains display specific characteristics that may not be extrapolated from results obtained on laboratory strains.
Process of Glucose Increases Rather Than Constant High Glucose Was the Main Cause of Abnormal Glucose Induced Glomerulus Epithelial Cells Inflammatory Response
Authors: Qi Jiancheng , Liu Weiyu , Gan Linli , Guo Hongrui , Xie Yue , Gou Liping , Cai Dongjie , Zhang Jizong , Deng Junliang , Ren Zhihua , Fang Jing , Zuo Zhicai
Published: December 2022

Abnormal glycemia is frequently along with nephritis, whose pathogenesis is unexplicit. Here, we investigated the effects of abnormal glucose on the renal glomerulus epithelial cells by stimulating immortalized bovine renal glomerulus epithelial (MDBK) cells with five different levels of glucose, including low glucose (2.5 mM for 48 h, LG), normal glucose (5 mM for 48 h, NG), high glucose (25 mM for 48 h, HG), increasing glucose (24 h of 2.5 mM glucose followed by 24 h of 25 mM, IG), and reducing glucose (24 h of 25 mM glucose followed by 24 h of 2.5 mM, RG). The results showed that LG and RG treatments had nonsignificant effects (p > 0.05) on the viability of MDBK cells. HG treatment decreased the viabilities of cells (p < 0.01) without triggering an apparent inflammatory response by activating the nox4/ROS/p53/caspase-3-mediated apoptosis pathway. IG treatment decreased the viabilities of cells significantly (p < 0.01) with high levels of pro-inflammatory cytokines IL-1β and IL-18 in the supernatant (p < 0.05) by triggering the txnip/nlrp3/gsdmd-mediated pyroptosis pathway. These results indicated that the process of glucose increase rather than the constant high glucose was the main cause of abnormal glucose-induced MDBK cell inflammatory death, prompting that the process of glycemia increases might be mainly responsible for the nephritis in diabetic nephropathy, underlining the importance of glycemic control in diabetes patients.
Growth Cessation and Dormancy Induction in Micropropagated Plantlets of Rheum rhaponticum ‘Raspberry’ Influenced by Photoperiod and Temperature
Authors: Wojtania Agnieszka , Markiewicz Monika , Waligórski Piotr
Published: December 2022

Dormancy development in micropropagated plantlets at the acclimatization stage and early growth ex vitro is undesirable as it lowers their survival rate and restricts the efficient year-round production of planting material. Thus far, little is known about the factors and mechanisms involved in the dormancy development of micropropagated herbaceous perennials, including rhubarb. This study determined physiological and molecular changes in the Rheum rhaponticum (culinary rhubarb) ‘Raspberry’ planting material in response to photoperiod and temperature. We found that the rhubarb plantlets that were grown under a 16-h photoperiod (LD) and a temperature within the normal growth range (17–23 °C) showed active growth of leaves and rhizomes and did not develop dormancy. Rapid growth cessation and dormancy development were observed in response to a 10-h photoperiod (SD) or elevated temperature under LD. These morphological changes were accompanied by enhanced abscisic acid (ABA) and starch levels and also the upregulation of various genes involved in carbohydrate synthesis and transport (SUS3, AMY3, BMY3, BGLU17) and ABA synthesis and signaling (ZEP and ABF2). We also found enhanced expression levels of heat shock transcription factors (HSFA2 and HSFA6B), heat shock proteins (HSP22, HSP70.1, HSP90.2 and HSP101) and antioxidant enzymes (PRX12, APX2 and GPX). This may suggest that dormancy induction in micropropagated rhubarb plantlets is a stress response to light deficiency and high temperatures and is endogenously coordinated by the ABA, carbohydrate and ROS pathways.
Synthesis, Photochemistry, Computational Study and Potential Application of New Styryl-Thiophene and Naphtho-Thiophene Benzylamines
Authors: Mlakić Milena , Odak Ilijana , Faraho Ivan , Bosnar Martina , Banjanac Mihailo , Lasić Zlata , Marinić Željko , Barić Danijela , Škorić Irena
Published: December 2022

In this research, the synthesis, photochemistry, and computational study of new cis- and trans-isomers of amino-thienostilbenes is performed to test the efficiency of their production and acid resistance, and to investigate their electronic structure, photoreactivity, photophysical characteristics, and potential biological activity. The electronic structure and conformations of synthesized thienostilbene amines and their photocyclization products are examined computationally, along with molecular modeling of amines possessing two thiophene rings that showed inhibitory potential toward cholinesterases. New amino-styryl thiophenes, with favorable photophysical properties and proven acid resistance, represent model compounds for their water-soluble ammonium salts as potential styryl optical dyes. The comparison with organic dyes possessing a trans-aminostilbene subunit as the scaffold shows that the newly synthesized trans-aminostilbenes have very similar absorbance wavelengths. Furthermore, their functionalized cis-isomers and photocyclization products are good candidates for cholinesterase inhibitors because of the structural similarity of the molecular skeleton to some already proven bioactive derivatives.
Isocitrate Dehydrogenase Alpha-1 Modulates Lifespan and Oxidative Stress Tolerance in Caenorhabditis elegans
Authors: Lin Zhi-Han , Chang Shun-Ya , Shen Wen-Chi , Lin Yen-Hung , Shen Chiu-Lun , Liao Sin-Bo , Liu Yu-Chun , Chen Chang-Shi , Ching Tsui-Ting , Wang Horng-Dar
Published: December 2022

Altered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by isocitrate dehydrogenase alpha-1 (idha-1) in the TCA cycle, increases lifespan in C. elegans. However, whether idha-1 can regulate lifespan in C. elegans remains unknown. Here, we reported that the expression of idha-1 modulates lifespan and oxidative stress tolerance in C. elegans. Transgenic overexpression of idha-1 extends lifespan, increases the levels of NADPH/NADP+ ratio, and elevates the tolerance to oxidative stress. Conversely, RNAi knockdown of idha-1 exhibits the opposite effects. In addition, the longevity of eat-2 (ad1116) mutant via dietary restriction (DR) was reduced by idha-1 knockdown, indicating that idha-1 may play a role in DR-mediated longevity. Furthermore, idha-1 mediated lifespan may depend on the target of rapamycin (TOR) signaling. Moreover, the phosphorylation levels of S6 kinase (p-S6K) inversely correlate with idha-1 expression, supporting that the idha-1-mediated lifespan regulation may involve the TOR signaling pathway. Together, our data provide new insights into the understanding of idha-1 new function in lifespan regulation probably via DR and TOR signaling and in oxidative stress tolerance in C. elegans.
Unveiling the circRNA-Mediated Immune Responses of Western Honey Bee Larvae to Ascosphaera apis Invasion
Authors: Ye Yaping , Fan Xiaoxue , Cai Zongbing , Wu Ying , Zhang Wende , Zhao Haodong , Guo Sijia , Feng Peilin , Li Qiming , Zou Peiyuan , Chen Mengjun , Fan Nian , Chen Dafu , Guo Rui
Published: December 2022

Western honey bee (Apis mellifera), a eusocial insect with a superior economic and ecological value, is widely used in the beekeeping industry throughout the world. As a new class of non-coding RNAs (ncRNAs), circular RNAs (circRNAs) participate in the modulation of considerable biological processes, such as the immune response via diverse manners. Here, the identification, characteristic investigation, and molecular verification of circRNAs in the Apis mellifera ligustica larval guts were conducted, and the expression pattern of larval circRNAs during the Ascosphaera apis infection was analyzed, followed by the exploration of the potential regulatory part of differentially expressed circRNAs (DEcircRNAs) in host immune responses. A total of 2083 circRNAs in the larval guts of A. m. ligustcia were identified, with a length distribution ranging from 106 nt to 92,798 nt. Among these, exonic circRNAs were the most abundant type and LG1 was the most distributed chromosome. Additionally, 25, 14, and 30 up-regulated circRNAs as well as 26, 25, and 62 down-regulated ones were identified in the A. apis-inoculated 4-, 5-, and 6-day-old larval guts in comparison with the corresponding un-inoculated larval guts. These DEcircRNAs were predicted to target 35, 70, and 129 source genes, which were relative to 12, 23, and 20 GO terms as well as 11, 10, and 27 KEGG pathways, including 5 cellular and humoral immune pathways containing apoptosis, autophagy, endocytosis, MAPK, Toll, and Imd signaling pathways. Furthermore, complex competing endogenous RNA (ceRNA) regulatory networks were detected to be formed among DEcircRNAs, DEmiRNAs, and DEmRNAs. The Target DEmRNAs were engaged in 24, 20, and 25 functional terms as well as 62, 80, and 159 pathways, including several vital immune defense-associated pathways, namely the lysosome, endocytosis, phagosome, autophagy, apoptosis, MAPK, Jak-STAT, Toll, and Imd signaling pathways. Finally, back-splicing sites within 15 circRNAs and the difference in the 9 DEcircRNAs’ expression between un-inoculated and A. apis-inoculated larval guts were confirmed utilizing molecular methods. These findings not only enrich our understanding of bee host-fungal pathogen interactions, but also lay a foundation for illuminating the mechanism underlying the DEcircRNA-mediated immune defense of A. m. ligustica larvae against A. apis invasion.
Targeting Lysosomes in Colorectal Cancer: Exploring the Anticancer Activity of a New Benzo[a]phenoxazine Derivative
Authors: Ferreira João C. C. , Granja Sara , Almeida Ana F. , Baltazar Fátima , Gonçalves M. Sameiro T. , Preto Ana , Sousa Maria João
Published: December 2022

Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.
Accumulation of Anthocyanins in Detached Leaves of Kalanchoë blossfeldiana: Relevance to the Effect of Methyl Jasmonate on This Process
Authors: Saniewski Marian , Szablińska-Piernik Joanna , Marasek-Ciołakowska Agnieszka , Mitrus Joanna , Góraj-Koniarska Justyna , Lahuta Lesław B. , Wiczkowski Wiesław , Miyamoto Kensuke , Ueda Junichi , Horbowicz Marcin
Published: December 2022

Accumulation of anthocyanins in detached leaves and in excised stems of Kalanchoë blossfeldiana kept under natural light conditions in the presence or absence of methyl jasmonate (JA-Me) was investigated. When the abaxial surface of detached leaves was held lower than the adaxial surface (the normal or natural position) under natural light conditions, anthocyanins were not accumulated on the abaxial side of the leaves. In contrast, when the adaxial surface of detached leaves was held lower than the abaxial surface (inverted position), anthocyanins were highly accumulated on the abaxial side of the leaves. These phenomena were independent of the growth stage of K. blossfeldiana as well as photoperiod. Application of JA-Me in lanolin paste significantly inhibited anthocyanin accumulation induced on the abaxial side of detached leaves held in an inverted position in a dose-dependent manner. Anthocyanin accumulation in the excised stem in response to natural light was also significantly inhibited by JA-Me in lanolin paste. Possible mechanisms of anthocyanin accumulation on the abaxial side of detached K. blossfeldiana leaves held in an inverted position under natural light conditions and the inhibitory effect of JA-Me on this process are described. The accompanying changes in the content of primary metabolites and histological analyses were also described.
The SDHD:p.H102R Variant Is Frequent in Russian Patients with Head and Neck Paragangliomas and Associated with Loss of 11p15.5 Region and Hypermethylation of H19-DMR
Authors: Snezhkina Anastasiya , Fedorova Maria , Kobelyatskaya Anastasiya , Markova Daria , Lantsova Margarita , Ikonnikova Anna , Emelyanova Marina , Kalinin Dmitry , Pudova Elena , Melnikova Nataliya , Dmitriev Alexey , Krasnov George , Pavlov Vladislav , Kudryavtseva Anna
Published: December 2022

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine neoplasms derived from the parasympathetic paraganglia of the head and neck. At least 30% of HNPGLs are linked to germline mutations, predominantly in SDHx genes. In this study, we analyzed an extended cohort of Russian patients with HNPGLs using whole-exome sequencing and found a highly frequent missense variant p.H102R in the SDHD gene. We determined this variant in 34% of the SDHD mutation carriers. This variant was associated with somatic loss of the gene wild-type allele. Data from the B allele frequency method and microsatellite and microdeletion analysis indicated evident LOH at the 11p15.5 region and potential loss of the whole of chromosome 11. We found hypermethylation of H19-DMR in all tumors, whereas differential methylation of KvDMR was mostly retained. These findings do not support the paternal transmission of SDHD:p.H102R but are in agreement with the Hensen model. Using targeted sequencing, we also studied the variant frequency in a control cohort; we found SDHD:p.H102R in 1.9% of cases, allowing us to classify this variant as pathogenic. The immunohistochemistry of SDHB showed that the SDHD:p.H102R mutation, even in combination with wild-type allele loss, does not always lead to SDH deficiency. The obtained results demonstrate the frequent variant associated with HNPGLs in a Russian population and support its pathogenicity. Our findings help with understanding the mechanism of tumorigenesis and are also important for the development of cost-effective genetic screening programs.
Quantifying the Detrimental Effects of Multiple Freeze/Thaw Cycles on Primary Human Lymphocyte Survival and Function
Authors: Serra Valentina , Fiorillo Edoardo , Cucca Francesco , Orrù Valeria
Published: December 2022

The use of cryopreserved peripheral blood mononuclear cells is common in biological research. It is widely accepted that primary cells are rendered unusable by several freezing cycles, although this practice might be very helpful when the biological material is valuable and its re-collection is impractical. To determine the extent to which primary cells undergoing repeated freezing cycles are comparable to one another and to fresh samples, we evaluated overall lymphocyte viability, their proliferation and cytokine production capabilities, as well as the levels of 27 cell subtypes in ten human peripheral blood mononuclear cells frozen for five years and repeatedly thawed. As expected, we observed a progressive increase in cell death percentages on three rounds of thawing, but the frequency of the main lymphocyte subsets was stable across the three thawings. Nevertheless, we observed a significant reduction of B cell frequency in frozen samples compared to fresh ones. On repeated thawings and subsequent conventional stimulation, lymphocyte proliferation significantly decreased, and IL-10, IL-6, GM-CSF, IFN-gamma, and IL-8 showed a trend to lower values.
Marine Collagen-Based Antibacterial Film Reinforced with Graphene and Iron Oxide Nanoparticles
Authors: Abdullah Johar Amin Ahmed , Yemişken Emre , Guerrero Antonio , Romero Alberto
Published: December 2022

It has become more widely available to use biopolymer-based films as alternatives to conventional plastic-based films due to their non-toxic properties, flexibility, and affordability. However, they are limited in application due to deficiencies in their properties. The marine collagen was the specimen for the present study. Thus, the main objective was to reinforce marine collagen-based films with 1.0% (w/w of the dry polymer weight) of iron oxide nanoparticles (IO-NPs), graphene oxide nanoparticles (GO-NPs), or a combination of both oxides (GO-NPs/IO-NPs) as antibacterial and antioxidant additives to overcome some of the limitations of the film. In this way, the nanoparticles were incorporated into the film-forming solution (2% w/v in acetic acid, 0.05 M) and processed by casting. Thereafter, the films were dried and analyzed for their physicochemical, mechanical, microstructural, and functional properties. The results show that the effective combination of GO-NPs/IO-NPs enhanced the physicochemical properties by increasing the water contact angle (WCA) of the films from 77.2 to 84.4° and their transparency (T) from 0.5 to 5.2. Furthermore, these nanoparticles added antioxidant and antibacterial value to the films, with free radical inhibition of up to 95.8% and 23.8 mm of bacteria growth inhibition (diameter). As a result, both types of nanoparticles are proposed as suitable additives to be incorporated into films and enhance their different properties.
Explainabilty Comparison between Random Forests and Neural Networks—Case Study of Amino Acid Volume Prediction
Authors: De Fazio Roberta , Di Giovannantonio Rosy , Bellini Emanuele , Marrone Stefano
Published: December 2022

As explainability seems to be the driver for a wiser adoption of Artificial Intelligence in healthcare and in critical applications, in general, a comprehensive study of this field is far from being completed. On one hand, a final definition and theoretical measurements of explainability have not been assessed, yet, on the other hand, some tools and frameworks for the practical evaluation of this feature are now present. This paper aims to present a concrete experience in using some of these explainability-related techniques in the problem of predicting the size of amino acids in real-world protein structures. In particular, the feature importance calculation embedded in Random Forest (RF) training is compared with the results of the Eli-5 tool applied to the Neural Network (NN) model. Both the predictors are trained on the same dataset, which is extracted from Protein Data Bank (PDB), considering 446 myoglobins structures and process it with several tools to implement a geometrical model and perform analyses on it. The comparison between the two models draws different conclusions about the residues’ geometry and their biological properties.
Lignin and Its Pathway-Associated Phytoalexins Modulate Plant Defense against Fungi
Authors: Ninkuu Vincent , Yan Jianpei , Fu Zenchao , Yang Tengfeng , Ziemah James , Ullrich Matthias S. , Kuhnert Nikolai , Zeng Hongmei
Published: December 2022

Fungi infections cause approximately 60–70% yield loss through diseases such as rice blast, powdery mildew, Fusarium rot, downy mildew, etc. Plants naturally respond to these infections by eliciting an array of protective metabolites to confer physical or chemical protection. Among plant metabolites, lignin, a phenolic compound, thickens the middle lamella and the secondary cell walls of plants to curtail fungi infection. The biosynthesis of monolignols (lignin monomers) is regulated by genes whose transcript abundance significantly improves plant defense against fungi. The catalytic activities of lignin biosynthetic enzymes also contribute to the accumulation of other defense compounds. Recent advances focus on modifying the lignin pathway to enhance plant growth and defense against pathogens. This review presents an overview of monolignol regulatory genes and their contributions to fungi immunity, as reported over the last five years. This review expands the frontiers in lignin pathway engineering to enhance plant defense.
Antifungal Activity and Biocontrol Potential of Simplicillium lamellicola JC-1 against Multiple Fungal Pathogens of Oilseed Rape
Authors: Li Wenting , Luo Tao , Li Juncheng , Zhang Jing , Wu Mingde , Yang Long , Li Guoqing
Published: December 2022

A fungal strain (JC-1) of Simplicillium was isolated from a pod of oilseed rape (Brassica napus) infested with the blackleg pathogen Leptosphaeria biglobosa. This study was done to clarify its taxonomic identity using morphological and molecular approaches, to characterize its antifungal activity through bioassays and genome-based identification of antifungal metabolites, and to determine its efficacy in inducing systemic resistance (ISR) in oilseed rape. The results showed that JC-1 belongs to Simplicillium lamellicola. It displayed a strong antagonistic relationship with L. biglobosa, Botrytis cinerea (gray mold) and Sclerotinia sclerotiorum (stem rot). The cultural filtrates of JC-1 showed a high efficacy in suppressing infection by S. sclerotiorum on detached leaves of oilseed rape. Genome analysis indicated that JC-1 has the capability of producing multiple antifungal metabolites, including aureobasidin A1, squalestatin S1 and verlamelin. Inoculation of JC-1 on seeds of oilseed rape caused a suppressive effect on infection by L. biglobosa on the cotyledons of the resulting seedlings, suggesting that JC-1 can trigger ISR. Endophytic growth, accumulation of anthocyanins, up-regulated expression of CHI (for chalcone isomerase) and PR1 (for pathogenesis-related protein 1), and down-regulated expression of NECD3 (for 9-cis-epoxycarotenoid dioxygenase) were detected to be associated with the ISR. This study provided new insights into the biocontrol potential and modes of action of S. lamellicola.