bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Polymeric Surfaces as Platforms for Streamlined Cancer Diagnostics in Liquid Biopsies
Authors: Ghorbanizamani Faezeh , Moulahoum Hichem , Guler Celik Emine , Zihnioglu Figen , Beduk Tutku , Goksel Tuncay , Turhan Kutsal , Timur Suna
Published: March 2023

Minimally invasive approaches for cancer diagnosis are an integral step in the quest to improve cancer survival. Liquid biopsies such as blood samples are matrices explored to extract valuable information about the tumor and its state through various indicators, such as proteins, peptides, tumor DNA, or circulating tumor cells. Although these markers are scarce, making their isolation and detection in complex matrices challenging, the development in polymer chemistry producing interesting structures, including molecularly imprinted polymers, branched polymers, nanopolymer composites, and hybrids, allowed the development of enhanced platforms with impressive performance for liquid biopsies analysis. This review describes the latest advances and developments in polymer synthesis and their application for minimally invasive cancer diagnosis. The polymer structures improve the operational performances of biosensors through various processes, such as increased affinity for enhanced sensitivity, improved binding, and avoidance of non-specific interactions for enhanced specificity. Furthermore, polymer-based materials can be a tremendous help in signal amplification of usually low-concentrated targets in the sample. The pros and cons of these materials, how the synthesis process affects their performance, and the device applications for liquid biopsies diagnosis will be critically reviewed to show the essentiality of this technology in oncology and clinical biomedicine.
Dual-Mode Biosensor for Simultaneous and Rapid Detection of Live and Whole Salmonella typhimurium Based on Bioluminescence and Fluorescence Detection
Authors: Xu Zhenli , Liu Bailu , Li Dengfeng , Yu Zhenzhong , Gan Ning
Published: March 2023

Both live and dead Salmonella typhimurium (S.T) are harmful to human health, but there are differences in pathological mechanism, dosage, and security. It is crucial to develop a rapid and simultaneous assay to distinguish and quantify live and dead S.T in foods. Herein, one dual-mode biosensor for simultaneous detection of live and dead S.T was fabricated based on two phage probes, using portable bioluminescence and fluorescent meter as detectors, respectively. Firstly, a magnetic phage capture probe (M-P1) and a phage signal tag (P2-S) labeled with SYTO 13 fluorescent dye were prepared, respectively. Both M-P1 and P2-S can specifically conjugate with S.T to form a magnetic sandwich complex. After magnetic separation, the isolated complex can emit a fluorescent signal under an excited 365 nm laser, which can reflect the total amount of S.T. Afterwards, the lysozyme was added to decompose the captured live S.T, which can release ATP and produce a bioluminescent signal corresponding to the live S.T amount. The dead S.T concentration can be deduced by the difference between total and live examples. The detection limit of 55 CFU/mL for total S.T and 9 CFU/mL for live ones was within 20 min. The assay was successfully employed in milk samples and prospectively for on-site screening of other dead and live bacteria, while changing the phages for the targets.
Recent Advancements of LSPR Fiber-Optic Biosensing: Combination Methods, Structure, and Prospects
Authors: Zhang Hongxin , Zhou Xue , Li Xuegang , Gong Pengqi , Zhang Yanan , Zhao Yong
Published: March 2023

Fiber-optic biosensors based on localized surface plasmon resonance (LSPR) have the advantages of great biocompatibility, label-free, strong stability, and real-time monitoring of various analytes. LSPR fiber-optic biosensors have attracted extensive research attention in the fields of environmental science, clinical medicine, disease diagnosis, and food safety. The latest development of LSPR fiber-optic biosensors in recent years has focused on the detection of clinical disease markers and the detection of various toxic substances in the environment and the progress of new sensitization mechanisms in LSPR fiber-optic sensors. Therefore, this paper reviews the LSPR fiber-optic sensors from the aspects of working principle, structure, and application fields in biosensors. According to the structure, the sensor can be divided into three categories: traditional ordinary optical fiber, special shape optical fiber, and specialty optical fiber. The advantages and disadvantages of existing and future LSPR fiber-optic biosensors are discussed in detail. Additionally, the prospect of future development of fiber-optic biosensors based on LSPR is addressed.
Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation
Authors: Liang Junjie , Han Shanshan , Ye Chao , Zhu Haimeng , Wu Jiajun , Nie Yunjuan , Chai Gaoshang , Zhao Peng , Zhang Dengxin
Published: March 2023

Postoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how to prevent POCD remains unclear. Minocycline, a commonly used antibiotic can cross the blood-brain barrier and exert an inhibitory effect on inflammation in the central nervous system. The present work aimed to examine the protective effect and mechanism of minocycline on sevoflurane-induced POCD in aged mice. We found that 3% sevoflurane administered 2 h a day for 3 consecutive days led to cognitive impairment in aged animals. Further investigation revealed that sevoflurane impaired synapse plasticity by causing apoptosis and neuroinflammation and thus induced cognitive dysfunction. However, minocycline pretreatment (50 mg/kg, i.p, 1 h prior to sevoflurane exposure) significantly attenuated learning and memory impairments associated with sevoflurane in aged animals by suppressing apoptosis and neuroinflammation. Moreover, a mechanistic analysis showed that minocycline suppressed sevoflurane-triggered neuroinflammation by inhibiting Notch signaling. Similar results were also obtained in vitro. Collectively, these findings suggested minocycline may be an effective drug for the prevention of sevoflurane-induced POCD in elderly patients.
Altered Postcentral Connectivity after Sleep Deprivation Correlates to Impaired Risk Perception: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Chen Jie , Gong Xinxin , Wang Letong , Xu Mengmeng , Zhong Xiao , Peng Ziyi , Song Tao , Xu Lin , Lian Jie , Shao Yongcong , Weng Xiechuan
Published: March 2023

Background: Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions’ communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired risk perception. Methods: Nineteen healthy male adults were recruited and underwent resting-state functional magnetic resonance imaging during a state of rested wakefulness and after nearly 36 h of total SD. They then completed the balloon analog risk task, which was used to measure the risk perception ability of risky decision-making. Regional homogeneity (ReHo) and voxel-wise functional connectivity were used to investigate neurobiological changes caused by SD. Correlation analysis was used to investigate the relationship between changes in ReHo, function, and risk perception. Results: At the behavioral level, risk perception decreased after 36 h of SD. At the neural level, SD induced a significant increase in ReHo in the right postcentral gyrus and was positively correlated with risk perception changes. The functional connectivity between the right postcentral gyrus, left medial temporal gyrus, and right inferior temporal gyrus was enhanced. Critically, increased right postcentral gyrus and right inferior temporal gyrus connectivity positively correlated with changes in risk perception. Conclusions: SD impairs the risk perception associated with altered postcentral connectivity. The brain requires more energy to process and integrate sensory and perceptual information after SD, which may be one possible reason for decreased risk perception ability after SD.
Novel Approaches to Memory and Aging: The Editorial
Authors: Padulo Caterina , Fairfield Beth
Published: March 2023

Heightened average life expectancy, which is increasing the number of older adults destined to live alone in the future, is forcing society to acknowledge the strong positive correlation between health costs and age [...]
Shared Leadership and Improvisation: Dual Perspective of Cognition-Affection
Authors: Zhang Dixuan , Wang Xiaohong , Zhang Shaopeng
Published: March 2023

Improvisation is an effective way to cope with rapid changes and obtain unexpected opportunities in a complex environment. Based on the cognitive-affective system theory, this study investigates the dual mediating role of cognitive flexibility and emotional intelligence between shared leadership and improvisation and the moderating role of promotion focus. We used multilevel and multi-sourced data to test the theoretical model and used a social network approach to measure shared leadership in teams. Our sample was comprised of 40 teams and 240 team members. The empirical findings indicated that cognitive flexibility and emotional intelligence mediated the relationship between shared leadership and improvisation; promotion focus moderated the relationship between shared leadership and improvisation, and the mediation effect via cognitive flexibility. This study contributes to expanding on improvisation research from the perspective of shared leadership and incorporating both the cognitive and the emotional process of the generation of improvisation into a theoretical framework from a compound perspective, which will open the black box for the mediation mechanism from shared leadership to improvisation. Furthermore, promotion focus is introduced into the research and creatively corresponds to the cognition-affection mediation mechanism, which expands the applicable scope of the regulatory focus theory.
Analysis of Academic Psychological Variables, Physical Education, and Physical Activity Levels of Mexican Students
Authors: Baños Raúl , Espinoza-Gutiérrez Roberto , Calleja-Núñez Juan José , Rodríguez-Cifuentes Gloria
Published: March 2023

Physical inactivity is a current worldwide, and especially Mexican adolescents. Therefore, this study has the following objectives: (i) to analyze the PA-LT pattern of Mexican adolescents; (ii) to analyze whether there are differences in emotional intelligence, basic psychological needs, academic motivation, self-esteem, and academic satisfaction according to the PA-LT pattern; (iii) to analyze the relationship between emotional intelligence, basic psychological needs, academic motivation, self-esteem, and academic satisfaction. A total of 748 secondary school students participated, of which 374 were girls (Mean age = 13.99; SD = 0.30) and 374 boys (Mean age = 14.02; SD = 0.33). The questionnaire comprised the following scales: IE, NPB-ESC, EMA, EA, and SIE. The main results obtained show that none of the girls stick to any active physical activity pattern during their spare time. In addition, physically active boys obtained better scores in emotional clarity, emotional repair, perception of academic competence, perception of social relationships, extrinsic motivation, intrinsic motivation, self-esteem, and satisfaction with school.
Optimal Design of Segment Storage and Hoisting of Precast Segmental Composite Box Girders with Corrugated Steel Webs
Authors: Song Qigang , Deng Wenqin , Liu Duo , Pei Huiteng , Peng Zongqing , Zhang Jiandong
Published: March 2023

To optimize the segment storage and hoisting plan of precast segmental composite box girders with corrugated steel web bridges, China’s first precast segmental composite girder bridge with corrugated steel webs is taken as the background. The difference between the precast segmental composite box girders with corrugated steel webs and the traditional concrete box girder is proven by numerical simulation. The stress and deformation characteristics of the segmental girder during storage and hoisting are analysed, and reasonable control measures are proposed. The data suggested that compared with ordinary concrete box girders, the smaller torsional stiffness and lateral stiffness of the precast segmental composite box girder with corrugated steel web segments lead to larger roof stress and deformation during the storage and hoisting periods. The number of storage layers of segmental girders should not exceed two, and the four hoisting point scheme should be adopted for hoisting. It is recommended to set one to two channel steel supports of no less than 20 grade steel between the top and bottom plates to avoid excessive deformation of the roof. With the increase in the segment length, the roof deformation and stress increased regardless of the storage period and the hoisting period. If the safety factor needs to be increased, when the segment length is short (1.6 m–3.2 m), increasing the support size is recommended. When the segment length is longer (4.0 m, 4.8 m), increasing the number of supports is recommended.
Influence of Small Radius Curved Shield Tunneling Excavation on Displacement of Surrounding Soil
Authors: Yang Bo , Zhang Chengyao , Su Na , Xiao Zhaoran
Published: March 2023

In contrast to straight tunnels, the mechanisms of displacement of surrounding soil induced by shield excavation of small radius curved tunnels are more complex. Based on field monitoring data of surface settlement and horizontal displacement of a small radius curved shield tunnel in a section of Zhengzhou Metro Line 3, a numerical model using three-dimensional a finite element method is established to evaluate factors of the displacement of surrounding soil. The results verify the validity of numerical simulation by comparison with field monitoring data and the influence of unbalanced additional thrust at tail jacks, curvature radius of a tunnel and tail grouting pressure on surface settlement and horizontal displacement of surrounding soil. Maximum surface settlement and horizontal displacement of surrounding soil at the outer side and inner side of curved tunnel axes are positively related to thrust ratio, while negatively related to curvature radius and grouting pressure. The ultimate objective of this study is to ascertain factors of displacement of surrounding soil induced by small radius shield excavation and provide a theoretical basis and technical support for the design and construction of similar tunnel.
Numerical Simulation of the Performance of Self-Healing Concrete in Beam Elements
Authors: Alkhuzai Khalid , Di Sarno Luigi , Haredy Abdullah , Alahmadi Raed , Albuhairi Danah
Published: March 2023

The formation of cracks in concrete structures occurs due to a multitude of causes ranging from shrinkage to external loading and environmental exposure. This phenomenon can significantly affect the lifecycle of concrete structures. Self-healing concrete (SHC) is considered a promoted innovation capable of overcoming this inevitable occurrence. In accordance with current SHC development processes, this paper utilizes the numerical simulation approach to test the performance of reinforced SHC beam specimens modeled using the commercial software ABAQUS 6.14 (Vélizy-Villacoublay, France). This paper aims to contribute to the scarce literature on SHC models by utilizing the overlooked dicyclopentadiene (DCPD) agent and ambiguous variability of crystalline admixtures. The SHC is introduced to the beam models at various depths and analyzed using load against displacement curves compared with a reference model of ordinary concrete. The effects of SHC on the mechanical properties of structural elements were determined. The results show a distinct improvement of the load-carrying capacity of SHC beams, indicating an efficient contribution of SHC in structural applications.
Viscoelastic Soil–Structure Interaction Procedure for Building on Footing Foundations Considering Consolidation Settlements
Authors: Lanes Ricardo Morais , Greco Marcelo , Almeida Valerio da Silva
Published: March 2023

This paper presents a numerical methodology to analyze frame structures supported on footing foundations subjected to slow strains caused by consolidation settlements. A building project on a subsurface layer of soft soil has been analyzed. The Boundary Element Method with the Mindlin fundamental solution has been applied to compute the displacement resulting from the interference between pressure bulbs on the foundation. The rheological Kelvin–Voigt model has also been used for soil–structure interactions. Terzaghi’s Theory of Consolidation was used to fit the displacement–time curves. Finally, the rheological model was coupled through an iterative procedure, employing structural non-linear geometric effects. The results are consistent with settlement predicted effects and revealed that the slow distribution of efforts can cause relevant increases in some regions in the structure of the building.
Cold Housing in Central Mexico: Environmental Dissatisfaction and Underheating Lowers Self-Perceived Health in Central Mexico
Authors: Zepeda-Gil Carlos , Montiel-Castro Augusto Jacobo
Published: March 2023

Despite being perceived as a warm country, winters in the Central Mexican Plateau frequently reach temperatures below zero Celsius. Prolonged exposures to low temperatures resulting in heart and respiratory morbidities are estimated to be responsible for 50% of the reported illness in the plateau, attributable primarily to the design of homes ill-suited to extreme temperatures. Consequently, there is a growing need to ensure that dwellings provide adequate indoor thermal conditions in the region. Hence, on-site sensors were used to collect temperature and relative humidity data every five minutes in 26 living rooms in the Plateau for 11 months. From these data, a subsample was determined, resulting in dwelling-level thermal comfort and health surveys on 15 homes. Computer simulations were used to investigate whether the building itself could provide thermal comfort under different retrofitting scenarios. Multiple linear regression relating the Predicted Percentage Dissatisfaction (PPD) index to self-perceived health was undertaken. Both monitored and simulated results were matched against our underheating model, finding that 92% of the homes had cold indoor environments, some even during summer. High PPD and intense levels of underheating were positive predictors of higher self-reported health problems. More self-reported health problems were correlated with both lower life satisfaction and self-worth, and with subjects’ use of more adaptive strategies against environmental dissatisfaction. Dynamic computer simulations suggested that indoor thermal environments could be improved by enforcing the non-utilised standard NOM-ENER-020, which recommends the addition of insulation on walls and roofs. These findings suggest that the cold environments within homes of the plateau influence the self-perceived physical and mental health of its population. Hence, the application of adequate measures, such as retrofitting homes with stronger standards than the existing NOM-ENER-020 are needed in place.
Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an ‘Immune Cold’ Phenotype Associated with Poor Survival
Authors: Porter Ross J. , Murray Graeme I. , Hapca Sandra , Hay Andrew , Craig Stephanie G. , Humphries Matthew P. , James Jacqueline A. , Salto-Tellez Manuel , Brice Daniel P. , Berry Susan H. , McLean Mairi H.
Published: March 2023

New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4+ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3+ (p < 0.001) and ICOS+ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8+ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an ‘immune cold’ tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC.
Non-Oncogene Addiction of KRAS-Mutant Cancers to IL-1β via Versican and Mononuclear IKKβ
Authors: Spella Magda , Ntaliarda Giannoula , Skiadas Georgios , Lamort Anne-Sophie , Vreka Malamati , Marazioti Antonia , Lilis Ioannis , Bouloukou Eleni , Giotopoulou Georgia A. , Pepe Mario A. A. , Weiss Stefanie A. I. , Petrera Agnese , Hauck Stefanie M. , Koch Ina , Lindner Michael , Hatz Rudolph A. , Behr Juergen , Arendt Kristina A. M. , Giopanou Ioanna , Brunn David , Savai Rajkumar , Jenne Dieter E. , de Château Maarten , Yull Fiona E. , Blackwell Timothy S. , Stathopoulos Georgios T.
Published: March 2023

Kirsten rat sarcoma virus (KRAS)-mutant cancers are frequent, metastatic, lethal, and largely undruggable. While interleukin (IL)-1β and nuclear factor (NF)-κB inhibition hold promise against cancer, untargeted treatments are not effective. Here, we show that human KRAS-mutant cancers are addicted to IL-1β via inflammatory versican signaling to macrophage inhibitor of NF-κB kinase (IKK) β. Human pan-cancer and experimental NF-κB reporter, transcriptome, and proteome screens reveal that KRAS-mutant tumors trigger macrophage IKKβ activation and IL-1β release via secretory versican. Tumor-specific versican silencing and macrophage-restricted IKKβ deletion prevents myeloid NF-κB activation and metastasis. Versican and IKKβ are mutually addicted and/or overexpressed in human cancers and possess diagnostic and prognostic power. Non-oncogene KRAS/IL-1β addiction is abolished by IL-1β and TLR1/2 inhibition, indicating cardinal and actionable roles for versican and IKKβ in metastasis.
Choice of Assessment and Subsequent Risk of Breast Cancer among Women with False-Positive Mammography Screening
Authors: Sardini Bayan , Fogh Jørgensen Susanne , Brønsro Larsen Lisbet , Elhakim Mohammad Talal , Njor Sisse Helle
Published: March 2023

Women with false-positive mammography screening results have a two- to four-fold higher risk of breast cancer. This study aimed to investigate if the subsequent risk of breast cancer after a false-positive mammography screening is associated with the received diagnostic assessment. The study population consisted of women who underwent false-positive mammography screening from January 2010 to June 2019. They were categorised into seven groups depending on the elements in the assessment (standard care: additional mammography, ultrasound, and if they had a relevant biopsy). Risks of interval cancer, next-round screen-detected cancer, and long-term breast cancer for non-standard care assessments were compared to standard care assessments using Binomial and Cox regression models. We included 44,279 women with a false-positive result. Invasive assessments that lacked an ultrasound or additional mammography were not more associated with an increased risk of subsequent cancers compared to that of ‘all three elements’. The few assessments that included ‘only ultrasound’ or ‘only mammography’ resulted in higher relative risks of next-round screen-detected cancer of 1.52 (95% CI: 0.93–2.47) and 1.67 (95% CI: 0.54–5.16), respectively, compared to that of standard care. The increased subsequent risk of breast cancer among women with a previous false-positive result was not found to be correlated with the choice of elements in the assessment process.
Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer
Authors: Markou A. N. , Londra D. , Stergiopoulou D. , Vamvakaris I. , Potaris K. , Pateras I. S. , Kotsakis A. , Georgoulias V. , Lianidou E.
Published: March 2023

Purpose: We assessed whether preoperativemutational analyses of circulating tumor cells (CTCs) and plasma-cfDNA could be used as minimally invasive biomarkers and as complimentary tools for early prediction of relapse in early-stage non-small -cell lung cancer (NSCLC). Experimental Design: Using ddPCR assays, hotspot mutations of BRAF, KRAS, EGFR and PIK3CA were identified in plasma-cfDNA samples and size-based enriched CTCs isolated from the same blood samples of 49 early-stage NSCLC patients before surgery and in a control group of healthy blood donors (n= 22). Direct concordance of the mutational spectrum was further evaluated in 27 patient-matched plasma-cfDNA and CTC-derived DNA in comparison to tissue-derived DNA. Results: The prevalence of detectable mutations of the four tested genes was higher in CTC-derived DNA than in the corresponding plasma-cfDNA (38.8% and 24.5%, respectively).The most commonly mutated gene was PIK3CA, in both CTCs and plasma-cfDNA at baseline and at the time of relapse. Direct comparison of the mutation status of selected drug-responsive genes in CTC-derived DNA, corresponding plasma-cfDNA and paired primary FFPE tissues clearly showed the impact of heterogeneity both within a sample type, as well as between different sample components. The incidence of relapse was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA compared with patients in whom no mutation was detected (p =0.023). Univariate analysis showed a significantly higher risk of progression (HR: 2.716; 95% CI, 1.030–7.165; p =0.043) in patients with detectable mutations in plasma-cfDNA compared with patients with undetectable mutations, whereas the hazard ratio was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA (HR: 3.375; 95% CI, 1.098–10.375; p =0.034). Conclusions: Simultaneous mutational analyses of plasma-cfDNA and CTC-derived DNA provided complementary molecular information from the same blood sample and greater diversity in genomic information for cancer treatment and prognosis. The detection of specific mutations in ctDNA and CTCs in patients with early-stage NSCLC before surgery was independently associated with disease recurrence, which represents an important stratification factor for future trials.
The Extracellular Matrix in Glioblastomas: A Glance at Its Structural Modifications in Shaping the Tumoral Microenvironment—A Systematic Review
Authors: Marino Salvatore , Menna Grazia , Di Bonaventura Rina , Lisi Lucia , Mattogno Pierpaolo , Figà Federica , Bilgin Lal , D’Alessandris Quintino Giorgio , Olivi Alessandro , Della Pepa Giuseppe Maria
Published: March 2023

Background and aim: While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM’s role in shaping tumoral development. Methods: An online literature search was launched on PubMed/Medline and Scopus using the research string “((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))”, and a systematic review was conducted in accordance with the PRISMA-P guidelines. Results: The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns. Conclusions: Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.
Evidence of Synergy Effects between Zinc and Copper Oxides with Acidic Sites on Natural Zeolite during Photocatalytic Oxidation of Ethylene Using Operando DRIFTS Studies
Authors: Abreu Norberto J. , Valdés Héctor , Zaror Claudio A. , de Oliveira Tatianne Ferreira , Azzolina-Jury Federico , Thibault-Starzyk Frédéric
Published: March 2023

In this article, the role of surface sites of modified zeolites with semiconductor nanoparticles as alternative photocatalyts for protecting post-harvest foodstuff from the detrimental effects of ethylene is addressed. Two single and one double catalyst based on zinc and copper oxides supported over modified zeolite samples were prepared. Physical, chemical, and surface properties of prepared materials were studied by several characterization methods. UV-Vis absorption spectra show that the applied modification procedures increase the optical absorption of light in the UV and visible regions, suggesting that an increase in the photocatalytic activity could take place mainly in the obtained co-impregnated catalyst. An ethylene conversion around 50% was achieved when the parent natural zeolite support was modified with both transition metal oxides, obtaining higher removal efficiency in comparison to single oxide catalysts. Adsorption and photocatalytic oxidation experiments were also performed using single and double catalysts supported over fumed silica, attaining lower ethylene conversion and thus highlighting the role of zeolite surfaces as adsorption sites for ethylene during photocatalytic reactions. Operando diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) studies reveal that a synergistic mechanism occurs, involving ethylene adsorption at acidic sites of zeolite and its photocatalytic oxidation due to the generation of radicals by the light activation of nanoparticles of zinc and copper oxides.
Comprehensive Study on Environmental Behaviour and Degradation by Photolytic/Photocatalytic Oxidation Processes of Pharmaceutical Memantine
Authors: Babić Sandra , Ljubas Davor , Mutavdžić Pavlović Dragana , Biošić Martina , Ćurković Lidija , Dabić Dario
Published: March 2023

Memantine is a pharmaceutical used to treat memory loss, one of the main symptoms of dementia and Alzheimer’s disease. The use of memantine is expected to continue to grow due to the increasing proportion of the elderly population worldwide. The aim of this work was to conduct a comprehensive study on the behaviour of memantine in the environment and the possibilities of its removal from wastewater. Abiotic elimination processes (hydrolysis, photolysis and sorption) of memantine in the environment were investigated. Results showed that memantine is stable in the environment and easily leached from river sediment. Therefore, further investigation was focused on memantine removal by advanced oxidation processes that would prevent its release into the environment. For photolytic and photocatalytic degradation of memantine, ultraviolet (UV) lamps with the predominant radiation wavelengths of 365 nm (UV-A) and 254/185 nm (UV-C) were used as a source of light. TiO2 in the form of a nanostructured film deposited on the borosilicate glass wall of the reactor was used for photocatalytic experiments. Photodegradation of memantine followed pseudo-first-order kinetics. The half-life of photocatalytic degradation by UV-A light was much higher (46.3 min) than the half-life obtained by UV-C light (3.9 min). Processes degradation efficiencies and evaluation of kinetic constants were based on the results of HPLC-MS/MS analyses, which also enable the identification of memantine oxidation products. The acute toxicity of the reaction mixture during the oxidation was evaluated by monitoring the inhibition of the luminescence of Vibrio fischeri bacteria. The results showed that memantine and its oxidation products were not harmful to Vibrio fischeri.
Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer
Authors: Nin Dawn Sijin , Deng Lih-Wen
Published: March 2023

Tumour-specific antigens have been an area of interest in cancer therapy since their discovery in the middle of the 20th century. In the era of immune-based cancer therapeutics, redirecting our immune cells to target these tumour-specific antigens has become even more relevant. Cancer-testis antigens (CTAs) are a class of antigens with an expression specific to the testis and cancer cells. CTAs have also been demonstrated to be expressed in a wide variety of cancers. Due to their frequency and specificity of expression in a multitude of cancers, CTAs have been particularly attractive as cancer-specific therapeutic targets. There is now a rapid expansion of CTAs being identified and many studies have been conducted to correlate CTA expression with cancer and therapy-resistant phenotypes. Furthermore, there is an increasing number of clinical trials involving using some of these CTAs as molecular targets in pharmacological and immune-targeted therapeutics for various cancers. This review will summarise the current knowledge of the biology of known CTAs in tumorigenesis and the regulation of CTA genes. CTAs as molecular targets and the therapeutic implications of these CTA-targeted anticancer strategies will also be discussed.
Intranasal Delivery of miR133b in a NEO100-Based Formulation Induces a Healing Response in Spinal Cord-Injured Mice
Authors: Danilov Camelia A. , Thein Thu Zan , Tahara Stanley M. , Schönthal Axel H. , Chen Thomas C.
Published: March 2023

Despite important advances in the pre-clinical animal studies investigating the neuroinhibitory microenvironment at the injury site, traumatic injury to the spinal cord remains a major problem with no concrete response. Here, we examined whether (1) intranasal (IN) administration of miR133b/Ago2 can reach the injury site and achieve a therapeutic effect and (2) NEO100-based formulation of miR133b/Ago2 can improve effectiveness. 24 h after a cervical contusion, C57BL6 female mice received IN delivery of miR133b/Ago2 or miR133b/Ago2/NEO100 for 3 days, one dose per day. The pharmacokinetics of miR133b in the spinal cord lesion was determined by RT-qPCR. The role of IN delivery of miR133b on motor function was assessed by the grip strength meter (GSM) and hanging tasks. The activity of miR133b at the lesion site was established by immunostaining of fibronectin 1 (FN1), a miR133b target. We found that IN delivery of miR133b/Ago2 (1) reaches the lesion scar and co-administration of miR133b with NEO100 facilitated the cellular uptake; (2) enhanced the motor function and addition of NEO100 potentiated this effect and (3) targeted FN1 expression at the lesion scar. Our results suggest a high efficacy of IN delivery of miR133b/Ago2 to the injured spinal cord that translates to improved healing with NEO100 further potentiating this effect.
The Combined Effects of Topography and Stiffness on Neuronal Differentiation and Maturation Using a Hydrogel Platform
Authors: Mattiassi Sabrina , Conner Abigail A. , Feng Fan , Goh Eyleen L. K. , Yim Evelyn K. F.
Published: March 2023

Biophysical parameters such as substrate topography and stiffness have been shown independently to elicit profound effects on neuronal differentiation and maturation from neural progenitor cells (NPCs) yet have not been investigated in combination. Here, the effects of various micrograting and stiffness combinations on neuronal differentiation and maturation were investigated using a polyacrylamide and N-acryloyl-6-aminocaproic acid copolymer (PAA-ACA) hydrogel with tunable stiffness. Whole laminin was conjugated onto the PAA-ACA surface indirectly or directly to facilitate long-term mouse and human NPC-derived neuron attachment. Three micrograting dimensions (2–10 µm) were patterned onto gels with varying stiffness (6.1–110.5 kPa) to evaluate the effects of topography, stiffness, and their interaction. The results demonstrate that the extracellular matrix (ECM)-modified PAA-ACA gels support mouse and human neuronal cell attachment throughout the differentiation and maturation stages (14 and 28 days, respectively). The interaction between topography and stiffness is shown to significantly increase the proportion of β-tubulin III (TUJ1) positive neurons and microtubule associated protein-2 (MAP2) positive neurite branching and length. Thus, the effects of topography and stiffness cannot be imparted. These results provide a novel platform for neural mechanobiology studies and emphasize the utility of optimizing numerous biophysical cues for improved neuronal yield in vitro.
BAG3: Nature’s Quintessential Multi-Functional Protein Functions as a Ubiquitous Intra-Cellular Glue
Authors: Brenner Caitlyn M. , Choudhary Muaaz , McCormick Michael G. , Cheung David , Landesberg Gavin P. , Wang Ju-Fang , Song Jianliang , Martin Thomas G. , Cheung Joseph Y. , Qu Hui-Qi , Hakonarson Hakon , Feldman Arthur M.
Published: March 2023

BAG3 is a 575 amino acid protein that is found throughout the animal kingdom and homologs have been identified in plants. The protein is expressed ubiquitously but is most prominent in cardiac muscle, skeletal muscle, the brain and in many cancers. We describe BAG3 as a quintessential multi-functional protein. It supports autophagy of both misfolded proteins and damaged organelles, inhibits apoptosis, maintains the homeostasis of the mitochondria, and facilitates excitation contraction coupling through the L-type calcium channel and the beta-adrenergic receptor. High levels of BAG3 are associated with insensitivity to chemotherapy in malignant cells whereas both loss of function and gain of function variants are associated with cardiomyopathy.
Topical Administration of Gardenia jasminoides Extract Regulates Th2 Immunity in OVA-Induced Mice
Authors: Park Sun Haeng , Song Hyun-Kyung , Ji Kon-Young , Jung Dong Ho , Jang Seol , Kim Taesoo , Kim Ho Kyoung
Published: March 2023

A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. Gardenia jasminoides extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.
Identification of Myelin Basic Protein Proximity Interactome Using TurboID Labeling Proteomics
Authors: Smirnova Evgeniya V. , Rakitina Tatiana V. , Ziganshin Rustam H. , Saratov George A. , Arapidi Georgij P. , Belogurov Alexey A. , Kudriaeva Anna A.
Published: March 2023

Myelin basic protein (MBP) is one of the key structural elements of the myelin sheath and has autoantigenic properties in multiple sclerosis (MS). Its intracellular interaction network is still partially deconvoluted due to the unfolded structure, abnormally basic charge, and specific cellular localization. Here we used the fusion protein of MBP with TurboID, an engineered biotin ligase that uses ATP to convert biotin to reactive biotin-AMP that covalently attaches to nearby proteins, to determine MBP interactome. Despite evident benefits, the proximity labeling proteomics technique generates high background noise, especially in the case of proteins tending to semi-specific interactions. In order to recognize unique MBP partners, we additionally mapped protein interaction networks for deaminated MBP variant and cyclin-dependent kinase inhibitor 1 (p21), mimicking MBP in terms of natively unfolded state, size and basic amino acid clusters. We found that in the plasma membrane region, MBP is colocalized with adhesion proteins occludin and myelin protein zero-like protein 1, solute carrier family transporters ZIP6 and SNAT1, Eph receptors ligand Ephrin-B1, and structural components of the vesicle transport machinery—synaptosomal-associated protein 23 (SNAP23), vesicle-associated membrane protein 3 (VAMP3), protein transport protein hSec23B and cytoplasmic dynein 1 heavy chain 1. We also detected that MBP potentially interacts with proteins involved in Fe2+ and lipid metabolism, namely, ganglioside GM2 activator protein, long-chain-fatty-acid-CoA ligase 4 (ACSL4), NADH-cytochrome b5 reductase 1 (CYB5R1) and metalloreductase STEAP3. Assuming the emerging role of ferroptosis and vesicle cargo docking in the development of autoimmune neurodegeneration, MBP may recruit and regulate the activity of these processes, thus, having a more inclusive role in the integrity of the myelin sheath.
Enrichment of Human Dermal Stem Cells from Primary Cell Cultures through the Elimination of Fibroblasts
Authors: Starzonek Christin , Mhamdi-Ghodbani Mouna , Henning Stefan , Bender Marc , Degenhardt Sarah , Chen I-Peng , Said Mohamed , Greinert Rüdiger , Volkmer Beate
Published: March 2023

Dermal stem cells (DSCs), which are progenitor cells of melanocytes, are isolated from human foreskin and cultivated as mixed cultures containing both DSCs and fibroblasts in varying proportions. These contaminating fibroblasts may have an impact on the results of experimental studies and are a serious limitation for certain applications. The aim of the present study was to purify or enrich DSCs—an indispensable step towards future investigations. Applying different methods, we demonstrated that highly enriched DSCs with a good recovery rate can be obtained through positive selection with MACS® immunomagnetic cell sorting. These DSCs remain vital and proliferate constantly in culture, maintaining a high level of purity after enrichment. Other approaches such as treatment with Geneticin or selective detachment were not suitable to purify DSC-fibroblast co-cultures. Overall, enriched DSCs represent a novel and unique model to study the effects of UV radiation on the differentiation of DSCs into melanocytes and their potential relevance in the genesis of malignant melanoma.
A Broad Spectral Photodetector Using Organic Bisindolo Quinoxaline on ZnO Nanorods
Authors: Li Ming-Hsien , Huang Yao-Hong , Chuang Chi-Chih , Lin Sang-Hao , Huang Yi-Hsuan , Lin Chia-Feng , Lin Yung-Sen , Kuo Ming-Yu , Chen Hsiang
Published: March 2023

Inorganic/organic hybrids of ZnO nanorods (NRs)/bisindolo quinoxaline (BIQ) were fabricated for broadband photosensing applications. Multiple material characterizations revealed the BIQ was self-assembled in a regular form of rod-like domain and an irregular form of amorphous aggregation that were distributed on the ZnO NRs. Optical measurements showed that BIQ can absorb visible light with a wavelength up to 630 nm and effectively generate photoelectrons. Moreover, clustering of BIQ can be observed via the 3D optical microscopy. ZnO/BIQ hybrids were promising for future UV and visible light environmental monitoring applications.
Primary Students’ Attitudes towards Peers with Disabilities in Physical Education in Saudi Arabia
Authors: Alhumaid Majed M.
Published: March 2023

The attitudes of students without disabilities toward their peers with disabilities are considered an important determinant of successful inclusion in physical education settings. Nonetheless, there is limited research on this topic in non-Western societies, especially in Arab contexts. Thus, to address this paucity in the literature, this study aimed to assess the general attitudes of Saudi students without disabilities towards their peers with disabilities and examine the associations between selected student-related variables (e.g., gender, age, type of school, school location, having a family member or a friend or a classmate with a disability, and having experience of playing with a person with a disability) and attitudes of students without disabilities. A total of 972 students aged 9–12 years old (Mage = 10.6; SD = 1.1; girls = 49.7%) completed the Arabic version of the Scale of Attitudes toward Students with Disabilities in Physical Education—Primary Education (SASDPE-PE). Data analysis indicated that, in general, participants reported positive attitudes toward their peers with disabilities in physical education classes. Despite boys being more likely to hold positive attitudes than girls, no significant difference between them existed. The results showed that 10-year-old participants reported more significantly positive attitudes than those in the other age groups. Participants attending public schools reported more significant positive attitudes toward their peers with disabilities in physical education classes compared to those attending private schools. Having a friend with a disability was linked to students without disabilities having positive attitudes towards their peers with disabilities. In contrast, having a family member or a classmate with disabilities and having played with a person with a disability were not related to such positive attitudes. The current study’s findings have significant implications for inclusive educational practices.