bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Fire Protection Techniques on Impact Resistance of Self-Compacting Concrete
Authors: Mathews Mervin Ealiyas , Kiran Tattukolla , Nammalvar Anand , Andrushia A. Diana , Alengaram U. Johnson
Published: June 2023

The present research investigates the behaviour of sustainable Self-Compacting Concrete (SCC) when subjected to high temperatures, focusing on workability, post-fire impact resistance, and the effects of fire protection coatings. To develop environmentally friendly SCC mixes, Supplementary Cementitious Materials (SCM) such as Fly Ash (FA), Ground Granulated Blast Furnace Slag (GGBFS), and Expanded Perlite Aggregate (EPA) were used. Fifty-six cubes and ninety-six impact SCC specimens were cast and cured for testing. Fire-resistant Cement Perlite Plaster (CPP) coatings were applied to the protected specimens, a passive protection coating rarely studied. SCC (unprotected and protected) specimens, i.e., protected and unprotected samples, were heated following the ISO standard fire curve. An extensive comparative study has been conducted on utilising different SCMs for developing SCC. Workability behaviour, post-fire impact resistance, and the influence of fire protection coatings on sustainable SCC subjected to high temperatures are the significant parameters examined in the present research, including physical observations and failure patterns. The test results noted that after 30 min of exposure, the unprotected specimen exhibited a significant decrease in failure impact energy, ranging from 80% to 90%. Furthermore, as the heating duration increased, there was a gradual rise in the loss of failure impact energy. However, when considering the protected CPP specimens, it was observed that they effectively mitigated the loss of strength when subjected to elevated temperature. Therefore, the findings of this research may have practical implications for the construction industry and contribute to the development of sustainable and fire-resistant SCC materials.
Enabling Technologies and Recent Advancements of Smart Facility Management
Authors: Olimat Hosam , Liu Hexu , Abudayyeh Osama
Published: June 2023

With various emerging technologies and integration possibilities, smart facility management has gained wide interest in recent years. Several technologies were introduced to support facilities management and improve decision-making, such as Building Information Modeling (BIM), Internet of Things (IoT), Digital Twin (DT), artificial intelligence (AI), and blockchain. Yet, facility managers still face challenges related to data handling and the actual implementation of these technologies. Thus, this paper explores the trends and integration possibilities of smart facilities management technologies to provide a deeper understanding of the current research state and the areas for future exploration. The Scopus database is utilized to collect literature data, and a bibliometric analysis is conducted on 7236 publications of different types, including conference publications, articles, reviews, and book chapters, using VOSviewer software. The results revealed a noticeable growth in the annual number of publications related to this field after 2018. BIM, IoT, and DT were seen to share the greatest research attention, with BIM being the dominant technology. With recent wide attention, blockchain technology is noticed to be introducing many integration possibilities. In addition, the prominent contributing authors, countries, and sources to this research area are also identified.
Satisfaction Evaluation for Underpass Green Spaces in Mountainous Cities under the Perspective of Environmental Perception
Authors: Zhang Junjie , Liu Junji , Yang Hong , Quan Junping , Wang Li , He Qixiao , Li Fanmiao
Published: June 2023

The overpasses and the terrain under them in Chongqing, a mountainous city in China, are complex and diverse, and some spaces under the overpasses are integrated and reconstructed into the underpass green space for citizens to stroll about or have a rest. From the perspective of visitor perception, this paper constructs a perception evaluation system of the environmental characteristics of underpass green space in mountainous cities from the following five environmental perception dimensions: path organization, security, aesthetic value, physical environment, activities and cultural. The IPA-Kano model is used to quantify environmental perception, and the main environmental factors affecting the improvement of recreation satisfaction of underpass green space in three types of terrain are explored, with a view to improving the environment and service functions of underpass green spaces in high-density interchange networks in mountainous cities, and enhancing the attractiveness of underpass green spaces. It can be found from the study that: (1) Among the five environmental perception dimensions, visitors pay more attention to the physical environment quality of the underpass green space and their physical and psychological activity experience, while their demands for visual senses are relatively low. Due to the deficiency or lack of leisure facilities, sports facilities, children’s playgrounds and amusement equipment, the dimension of “activities and cultural perception” of the underpass green space has the lowest scores of all. (2) The existing sites, facilities and landscape resources of the underpass green space, different terrain types and underpass environment are the important reasons that affect the performance of environmental perception factors and their priority ranking results. (3) The improvement of security of the arrival path or sports facilities is beneficial to improve visitor satisfaction of underpass green space of three types of terrain. The number of environmental factors to be optimized of the three types of terrain are ranked as: mountainous green space > flat green space > concave green space. Among them, four environmental factors have a high priority in two kinds of underpass green space, which are the distribution and quantity of leisure facilities, the effect of noise reduction and sound insulation, the adequacy of activity venues and the distribution and quantity of sports facilities. Finally, according to the particularity of the underpass environment and the characteristics of three types of terrain, this paper puts forward some suggestions for optimizing the service function of underpass green space from five perceptual dimensions.
Vulnerability Analysis of Main Aftershock Sequence of Aqueduct Based on Incremental Dynamic Analysis Method
Authors: Zheng Xiaodong , Shen Yiming , Zong Xingguang , Su Hui , Zhao Xun
Published: June 2023

At present, traditional seismic design methods often ignore the structural damage caused by aftershocks in the evaluation of structural stability. In this paper, seven main aftershock sequences were constructed by using the attenuation method. The incremental dynamic analysis method (IDA) was used to analyze the nonlinear dynamic time history of the aqueduct structure. The main aftershock vulnerability curve of the aqueduct structure was obtained by taking the seismic intensity IM and the maximum ratio of the plastic strain energy to the total strain energy Dp as the structural performance parameter. The analysis results show that the residual displacement of the aqueduct increases by 33%, 66%, 44%, 37%, 0.01%, 60%, and 59%, respectively, under the seven main aftershock sequences. The incremental damage percentages of the aftershock at the end of the period were 9.85%, 15.00%, 26.53%, 2.10%, 0.9%, 35.97%, and 9.85%, respectively. The main aftershock made the damage at the bottom of the arch and the aqueduct more extensive. When the earthquake intensity is 0.3 g, the exceedance probabilities of moderate damage and severe damage are 62.68% and 14.39%, respectively, under the action of the main aftershock sequence. The exceedance probabilities under the action of the main aftershock sequence are 38.52% and 12.08% higher than that of the single main earthquake, respectively.
Comparative Assessment of Performance-Based Design Methodologies Applied to a R.C. Shear-Wall Building
Authors: Vielma-Quintero Juan C. , Carvallo Jorge , Vielma Juan C.
Published: June 2023

Performance-based design has been increasingly used in practice due to computational improvements, the sophistication and dissemination of nonlinear analysis methods, and the development of commercial programs that facilitate its use. We can evaluate the nonlinear effects of seismic events of great magnitude on the structural behavior of a building, verify preliminary designs based on force-based methods, validate standard design regulations, determine deformations, and calculate accelerations that can be translated into parameters of structural damage and economic losses, among other functions. Guiding documents have presented methodologies to establish requirements, evaluation criteria, analysis methods, etc., each with different objectives, revealing the lack of a consensus method. In this paper, the state of the art of performance-based design is studied, and some of the most relevant methods, such as ASCE 41-17, ASCE 7-16, and the alternative procedure of ACHISINA, are applied to a structure with shear walls designed according to current Chilean regulations. Additionally, modal-response spectrum analysis is used. The modeling of the earthquake-resistant structure of the building, the preparation of seismic records, and the consideration of aspects that limit the rigorous application of the method are addressed in a nonelastic analysis framework. Results obtained in the respective analyses that are used to evaluate the structural performance are compared with the corresponding performance criteria for each standard, considering the characteristics of each methodology. Moreover, the main complications that can occur during the application of the methods are discussed.
The Policy Impact of Carbon Emission Trading on Building Enterprises’ Total Factor Productivity in China
Authors: Tian Jinzhao , Liu Yisheng , Li Anlin
Published: June 2023

Nearly 40 percent of worldwide energy and process-related CO2 emissions are produced by the construction sector. China’s construction industry is the largest in the world, with Chinese construction enterprises completing a total output value of RMB 26.39 trillion in 2020; these buildings contribute to about 20 percent of China’s overall carbon emissions and 20 percent of the global total emissions. There is an urgent need to prove whether construction enterprises are benefiting from the carbon trading policy. Compared to the traditional method, a double difference model can be used to highlight the consequences of different states of construction enterprises’ responses to carbon trading regimes. In this study, we examine the following results based on cross-sectional data collected from 2006 to 2021, from listed construction enterprises: (1) Existing carbon emission policies have had a significant impact on the improvement of construction enterprises’ total factor productivity. This improvement is more pronounced in large state-owned enterprises in particular. (2) Construction enterprises’ greater involvement in carbon trading income is most strongly influenced by their green innovation level. (3) Construction enterprises located in eastern and central China benefit significantly from carbon trading, but construction enterprises based in the west do not. The research result indicates that future incentive initiatives should pay more attention to western regions and privately owned building enterprises. The leading role of large state-owned building enterprises should be reinforced.
Vulnerability of Affordable Housing to Global Warming in South Africa: Case Study of a Masonry House in Johannesburg
Authors: Bradley Ryan
Published: June 2023

Global warming is expected to lead to longer and more intense heatwaves, which will have negative environmental and socioeconomic impacts around the world. South Africa is projected to experience significant warming, with surface temperatures possibly increasing by up to 3 °C by mid-century. This warming trend has implications for architecture, as the demand for cooling in buildings could rise dramatically. However, socioeconomic conditions in developing countries may limit the use of air conditioning to mitigate indoor overheating. In South Africa, research has shown that government provided low-cost housing structures are thermally inefficient, with temperatures occasionally exceeding outdoor levels. Residents often rely on natural ventilation and personal actions to cope with heat. However, the effects of climate change may render these strategies insufficient if energy poverty and housing improvement are not addressed. This study aims to examine the impact of global warming on a high mass, naturally ventilated, affordable housing structure in Johannesburg, South Africa. Measured operative temperature data from a long-term experimental study, alongside adaptive temperature limits to evaluate overheating, highlight the vulnerability of indoor spaces without adequate insulation and/or thermal mass. The results underscore concerns about the performance of low-cost and affordable housing in warmer future climates in the South African interior.
Response of Masonry-Infilled Reinforced Concrete Frames Strengthened at Interfaces with Geo-Fabric under In-Plane Loads
Authors: Sreekeshava K. S. , Rodrigues Hugo , Arunkumar A. S.
Published: June 2023

The interfaces between masonry infill and reinforced concrete (MI-RC) frames are identified as the weakest regions under lateral loads. Hence, the behavior of such frames under lateral loads can be understood mainly through experimental investigations. The deformation demands induced by horizontal loads on RC frames with infill masonry walls change due to contact losses between the infill masonry and the RC frames. This can be controlled by providing proper reinforcements at the interfaces. In the present experimental investigation, three half-scaled models subjected to reversed cyclic lateral in-plane loads were tested. In detail, the specimens considered are the MI-RC frame model, an MI-RC frame with geo-fabric reinforcement at the interface and an MI-RC frame with geo-fabric reinforcement at interfaces with an open ground story. The models were subjected to reversed cyclic lateral in-plane loads, and the post-yield responses of the models with respect to stiffness degradation, drift, energy dissipation, ductility and failure mode have been discussed.
Insights into Urologic Cancer
Authors: Klümper Niklas , Ellinger Jörg
Published: June 2023

Collectively, urological malignancies account for a considerable proportion of cancer cases worldwide [...]
The Molecular Basis and Clinical Consequences of Chronic Inflammation in Prostatic Diseases: Prostatitis, Benign Prostatic Hyperplasia, and Prostate Cancer
Authors: Oseni Saheed Oluwasina , Naar Corey , Pavlović Mirjana , Asghar Waseem , Hartmann James X. , Fields Gregg B. , Esiobu Nwadiuto , Kumi-Diaka James
Published: June 2023

Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases.
Alternative mRNA Splicing Controls the Functions of the Histone H3K27 Demethylase UTX/KDM6A
Authors: Fotouhi Omid , Nizamuddin Sheikh , Falk Stephanie , Schilling Oliver , Knüchel-Clarke Ruth , Biniossek Martin L. , Timmers H. T. Marc
Published: June 2023

The UTX/KDM6A histone H3K27 demethylase plays an important role in development and is frequently mutated in cancers such as urothelial cancer. Despite many studies on UTX proteins, variations in mRNA splicing have been overlooked. Using Nanopore sequencing, we present a comprehensive analysis of UTX/KDM6A splicing events in human cell lines and in tissue samples from bladder cancer cases and normal epithelia. We found that the central region of UTX mRNAs encoded by exons 12 to 17 undergoes extensive alternative splicing. Up to half of all stable mRNAs (8–48% in bladder tissues and 18–58% in cell lines) are represented by the UTX canonical isoform lacking exon 14 encoding a nuclear localization sequence, and hence exon 14-containing UTX isoforms exclusively localize to the nucleus, unlike the cytonuclear localization of the canonical isoform. Chromatin association was also higher for exon-14-containing isoforms compared to the canonical UTX. Using quantitative mass spectrometry, we found that all UTX isoforms integrated into the MLL3 and MLL4, PR-DUB and MiDAC complexes. Interestingly, one of the novel UTX isoforms, which lacks exons 14 and 16, fails to interact with PR-DUB and MiDAC complex members. In conclusion, UTX mRNAs undergo extensive alternative splicing, which controls the subcellular localization of UTX and its interactions with other chromatin regulatory complexes.
Identification of Key Elements in Prostate Cancer for Ontology Building via a Multidisciplinary Consensus Agreement
Authors: Moreno Amy , Solanki Abhishek A. , Xu Tianlin , Lin Ruitao , Palta Jatinder , Daugherty Emily , Hong David , Hong Julian , Kamran Sophia C. , Katsoulakis Evangelia , Brock Kristy , Feng Mary , Fuller Clifton , Mayo Charles , BDSC Prostate Cancer BDSC Prostate Cancer
Published: June 2023

Background: Clinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research. Methods: A modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM). Results: The panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM. Conclusions: This expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC).
The Risk of Venous Thromboembolism in Korean Patients with Breast Cancer: A Single-Center Experience
Authors: Park Jung Ho , Ahn So Eun , Kwon Lyo Min , Ko Ho Hyun , Kim Sanghwa , Suh Yong Joon , Kim Ho Young , Park Kyoung-Ha , Kim Doyil
Published: June 2023

The relationship between cancer and venous thromboembolism (VTE) has long been described. The risk of VTE in Asian patients with breast cancer remains largely unknown. This study described the incidence and risk factors of VTE in Korean patients with breast cancer. Data were collected from a retrospective database of patients who underwent breast cancer surgery between 2011 and 2020 at a single institution. The Cox proportional-hazards model was used to identify factors associated with VTE occurrences. Among the 2246 patients with breast cancer, 48 (2.1%) developed VTE during a median follow-up period of 53 months. The average incidence of VTE was 459 per 100,000 person-years. Age ≥ 60 years, male sex, chronic kidney disease, reconstructive procedures, and stage II or higher were independent predictive factors for VTE. VTE was associated with poor disease-free survival (hazard ratio (HR), 6.140; 95% confidence interval (CI), 3.480–10.835), and overall survival (HR, 8.842; 95% CI 4.386–17.824). Most VTE events were manageable with anticoagulation; three (6.3%) patients died of VTE, despite intensive care. The incidence of VTE was significantly elevated in Korean patients with breast cancer. Since VTE has a negative effect on oncologic outcomes of breast cancer, clinicians should manage its risk throughout their lifetime.
GTN Enhances Antitumor Effects of Doxorubicin in TNBC by Targeting the Immunosuppressive Activity of PMN-MDSC
Authors: Mabrouk Nesrine , Racoeur Cindy , Shan Jingxuan , Massot Aurélie , Ghione Silvia , Privat Malorie , Dondaine Lucile , Ballot Elise , Truntzer Caroline , Boidot Romain , Hermetet François , Derangère Valentin , Bruchard Mélanie , Végran Frédérique , Chouchane Lotfi , Ghiringhelli François , Bettaieb Ali , Paul Catherine
Published: June 2023

(1) Background: Immunosuppression is a key barrier to effective anti-cancer therapies, particularly in triple-negative breast cancer (TNBC), an aggressive and difficult to treat form of breast cancer. We investigated here whether the combination of doxorubicin, a standard chemotherapy in TNBC with glyceryltrinitrate (GTN), a nitric oxide (NO) donor, could overcome chemotherapy resistance and highlight the mechanisms involved in a mouse model of TNBC. (2) Methods: Balb/C-bearing subcutaneous 4T1 (TNBC) tumors were treated with doxorubicin (8 mg/Kg) and GTN (5 mg/kg) and monitored for tumor growth and tumor-infiltrating immune cells. The effect of treatments on MDSCs reprogramming was investigated ex vivo and in vitro. (3) Results: GTN improved the anti-tumor efficacy of doxorubicin in TNBC tumors. This combination increases the intra-tumor recruitment and activation of CD8+ lymphocytes and dampens the immunosuppressive function of PMN-MDSCs PD-L1low. Mechanistically, in PMN-MDSC, the doxorubicin/GTN combination reduced STAT5 phosphorylation, while GTN +/− doxorubicin induced a ROS-dependent cleavage of STAT5 associated with a decrease in FATP2. (4) Conclusion: We have identified a new combination enhancing the immune-mediated anticancer therapy in a TNBC mouse model through the reprograming of PMN-MDSCs towards a less immunosuppressive phenotype. These findings prompt the testing of GTN combined with chemotherapies as an adjuvant in TNBC patients experiencing treatment failure.
Role of Nanocellulose in Light Harvesting and Artificial Photosynthesis
Authors: Samyn Pieter , Rastogi Vibhore Kumar , Baba Neelisetty Sesha Sai , Van Erps Jürgen
Published: June 2023

Artificial photosynthesis has rapidly developed as an actual field of research, mimicking natural photosynthesis processes in plants or bacteria to produce energy or high-value chemicals. The nanocelluloses are a family of biorenewable materials that can be engineered into nanostructures with favorable properties to serve as a host matrix for encapsulation of photoreactive moieties or cells. In this review, the production of different nanocellulose structures such as films, hydrogels, membranes, and foams together with their specific properties to function as photosynthetic devices are described. In particular, the nanocellulose’s water affinity, high surface area and porosity, mechanical stability in aqueous environment, and barrier properties can be tuned by appropriate processing. From a more fundamental viewpoint, the optical properties (transparency and haze) and interaction of light with nanofibrous structures can be further optimized to enhance light harvesting, e.g., by functionalization or appropriate surface texturing. After reviewing the basic principles of natural photosynthesis and photon interactions, it is described how they can be transferred into nanocellulose structures serving as a platform for immobilization of photoreactive moieties. Using photoreactive centers, the isolated reactive protein complexes can be applied in artificial bio-hybrid nanocellulose systems through self-assembly, or metal nanoparticles, metal-organic frameworks, and quantum dots can be integrated in nanocellulose composites. Alternatively, the immobilization of algae or cyanobacteria in nanopaper coatings or a porous nanocellulose matrix allows to design photosynthetic cell factories and advanced artificial leaves. The remaining challenges in upscaling and improving photosynthesis efficiency are finally addressed in order to establish a breakthrough in utilization of nanocellulose for artificial photosynthesis.
Vanadium Complexes Derived from O,N,O-tridentate 6-bis(o-hydroxyalkyl/aryl)pyridines: Structural Studies and Use in the Ring-Opening Polymerization of ε-Caprolactone and Ethylene Polymerization
Authors: Elsegood Mark R. J. , Clegg William , Redshaw Carl
Published: June 2023

Interaction of [VO(OiPr)3] with 6-bis(o-hydroxyaryl)pyridine, 2,6-{HOC(Ph)2CH2}2(NC5H3), LH2, afforded [VO(OiPr)L] (1) in good yield. The reaction of LNa2, generated in-situ from LH2 and NaH, with [VCl3(THF)3] led to the isolation of [VL2] (2) in which the pyridyl nitrogen atoms are cis; a regioisomer 3∙2THF, in which the pyridyl nitrogen atoms are trans, was isolated when using [VCl2(TMEDA)2]. The reaction of the 2,6-bis(o-hydroxyalkyl)pyridine {HOC(iPr)2CH2}2(NC5H3), L1H2, with [VO(OR)3] (R = nPr, iPr) led, following work-up, to [VO(OR)L1] (R = nPr (4), iPr (5)). Use of the bis(methylpyridine)-substituted alcohol (tBu)C(OH)[CH2(C5H3Me-5)]2, L2H, with [VO(OR)3] (R = Et, iPr) led to the isolation of [VO(μ-O)(L2)]2 (6). Complexes 1 to 6 have been screened for their ability to act as pre-catalysts for the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL), and rac-lactide (r-LA) and compared against the known catalyst [Ti(OiPr)2L] (I). Complexes 1, 4–6 were also screened as catalysts for the polymerization of ethylene (in the presence of dimethylaluminium chloride/ethyltrichloroacetate). For the ROP of ε-CL, in toluene solution, conversions were low to moderate, affording low molecular weight products, whilst as melts, the systems were more active and afforded higher molecular weight polymers. For δ-VL, the systems run as melts afforded good conversions, but in the case of r-LA, all systems as melts exhibited low conversions (<10%) except for 6 (<54%) and I (<39%). In the case of ethylene polymerization, the highest activity (8600 Kg·mol·V−1bar−1h−1) was exhibited by 1 in dichloromethane, affording high molecular weight, linear polyethylene at 70 °C. In the case of 4 and 5, which contain the propyl-bearing chelates, the activities were somewhat lower (≤1500 Kg·mol·V−1bar−1h−1), whilst 6 was found to be inactive.
Sulfonated Silica Coated CoFe2O4 Magnetic Nanoparticles for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-One and Octahydroquinazoline Derivatives
Authors: Afshari Mozhgan , Carabineiro Sónia A. C. , Gorjizadeh Maryam
Published: June 2023

Sulfonated-silica-coated cobalt ferrite (CoFe2O4) magnetic nanoparticles (MNPs-SiCoFe-SO3H) are efficient heterogeneous catalysts for the synthesis of 3,4-dihydropyrimidin-2(1H)-one and octahydroquinazoline derivatives in the absence of solvent. The effects of solvent, temperature, and catalyst amount on the reaction are investigated. The easy separation, reusability of the catalyst, simplicity of the procedure, mild reaction conditions, and good yields (68–95%) within short reaction times (15–70 min) are the advantages of this method. The catalyst can be reused up to eight times with not much loss of activity. Scanning electron microscopy images, X-ray diffraction spectra, and elemental analysis of the recycled catalyst show that the catalyst is stable after the reaction.
Updates on the Physiopathology of Group I Metabotropic Glutamate Receptors (mGluRI)-Dependent Long-Term Depression
Authors: Mango Dalila , Ledonne Ada
Published: June 2023

Group I metabotropic glutamate receptors (mGluRI), including mGluR1 and mGluR5 subtypes, modulate essential brain functions by affecting neuronal excitability, intracellular calcium dynamics, protein synthesis, dendritic spine formation, and synaptic transmission and plasticity. Nowadays, it is well appreciated that the mGluRI-dependent long-term depression (LTD) of glutamatergic synaptic transmission (mGluRI-LTD) is a key mechanism by which mGluRI shapes connectivity in various cerebral circuitries, directing complex brain functions and behaviors, and that it is deranged in several neurological and psychiatric illnesses, including neurodevelopmental disorders, neurodegenerative diseases, and psychopathologies. Here, we will provide an updated overview of the physiopathology of mGluRI-LTD, by describing mechanisms of induction and regulation by endogenous mGluRI interactors, as well as functional physiological implications and pathological deviations.
Phospholipid Encapsulation of an Anti-Fibrotic Endopeptide to Enhance Cellular Uptake and Myocardial Retention
Authors: Sonkawade Swati D. , Xu Shirley , Kim Minhyung , Nepali Sarmila , Karambizi Victoire-Grace , Sexton Sandra , Turowski Steven G. , Li Kunpeng , Spernyak Joseph A. , Lovell Jonathan F. , George Anthony , Suwal Sujit , Sharma Umesh C. , Pokharel Saraswati
Published: June 2023

Background: Cardioprotective effects of N-acetyl-ser-asp-lys-pro (Ac-SDKP) have been reported in preclinical models of myocardial remodeling. However, the rapid degradation of this endogenous peptide in vivo limits its clinical use. Method: To prolong its bioavailability, Ac-SDKP was encapsulated by phosphocholine lipid bilayers (liposomes) similar to mammalian cell membranes. The physical properties of the liposome structures were assessed by dynamic light scattering and scanning electron microscopy. The uptake of Ac-SDKP by RAW 264.7 macrophages and human and murine primary cardiac fibroblasts was confirmed by fluorescence microscopy and flow cytometry. Spectrum computerized tomography and competitive enzyme-linked immunoassays were performed to measure the ex vivo cardiac biodistribution of Ac-SDKP. The biological effects of this novel synthetic compound were examined in cultured macrophages and cardiac fibroblasts and in a murine model of acute myocardial infarction induced by permanent coronary artery ligation. Results: A liposome formulation resulted in the greater uptake of Ac-SDKP than the naked peptide by cultured RAW 264.7 macrophages and cardiac fibroblasts. Liposome-delivered Ac-SDKP decreased fibroinflammatory genes in cultured cardiac fibroblasts co-treated with TGF-β1 and macrophages stimulated with LPS. Serial tissue and serum immunoassays showed the high bioavailability of Ac-SDKP in mouse myocardium and in circulation. Liposome-delivered Ac-SDKP improved cardiac function and reduced myocardial fibroinflammatory responses in mice with acute myocardial infarction. Conclusion: Encapsulation of Ac-SDKP in a cell membrane-like phospholipid bilayer enhances its plasma and tissue bioavailability and offers cardioprotection against ischemic myocardial injury. Future clinical trials can use this novel approach to test small protective endogenous peptides in myocardial remodeling.
The Prodigious Potential of mRNA Electrotransfer as a Substitute to Conventional DNA-Based Transient Transfection
Authors: Juncker Théo , Chatton Bruno , Donzeau Mariel
Published: June 2023

Transient transfection of foreign DNA is the most widely used laboratory technique to study gene function and product. However, the transfection efficiency depends on many parameters, including DNA quantity and quality, transfection methods and target cell lines. Here, we describe the considerable advantage of mRNA electroporation compared to conventional DNA-based systems. Indeed, our methodology offers extremely high transfection efficiency up to 98% regardless of the cell line tested. Protein expression takes place a few hours post-transfection and lasts over 72 h, but overall, the electrotransfer of mRNAs enables the monitoring of the level of protein expressed by simply modulating the amount of mRNAs used. As a result, we successfully conducted cell imaging by matching the levels of expressed VHHs and the antigen present in the cell, preventing the necessity to remove the excess unbound VHHs. Altogether, our results demonstrate that mRNA electrotransfer could easily supplant the conventional DNA-based transient expression system.
Astrocytes Differentiated from LRRK2-I1371V Parkinson’s-Disease-Induced Pluripotent Stem Cells Exhibit Similar Yield but Cell-Intrinsic Dysfunction in Glutamate Uptake and Metabolism, ATP Generation, and Nrf2-Mediated Glutathione Machinery
Authors: Banerjee Roon , Raj Aishwarya , Potdar Chandrakanta , Pal Pramod , Yadav Ravi , Kamble Nitish , Holla Vikram , Datta Indrani
Published: June 2023

Owing to the presence of multiple enzymatic domains, LRRK2 has been associated with a diverse set of cellular functions and signaling pathways. It also has several pathological mutant-variants, and their incidences show ethnicity biases and drug-response differences with expression in dopaminergic-neurons and astrocytes. Here, we aimed to assess the cell-intrinsic effect of the LRRK2-I1371V mutant variant, prevalent in East Asian populations, on astrocyte yield and biology, involving Nrf2-mediated glutathione machinery, glutamate uptake and metabolism, and ATP generation in astrocytes derived from LRRK2-I1371V PD patient iPSCs and independently confirmed in LRRK2-I1371V-overexpressed U87 cells. Astrocyte yield (GFAP-immunopositive) was comparable between LRRK2-I1371V and healthy control (HC) populations; however, the astrocytic capability to mitigate oxidative stress in terms of glutathione content was significantly reduced in the mutant astrocytes, along with a reduction in the gene expression of the enzymes involved in glutathione machinery and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Simultaneously, a significant decrease in glutamate uptake was observed in LRRK2-I1371V astrocytes, with lower gene expression of glutamate transporters SLC1A2 and SLC1A3. The reduction in the protein expression of SLC1A2 was also directly confirmed. Enzymes catalyzing the generation of γ glutamyl cysteine (precursor of glutathione) from glutamate and the metabolism of glutamate to enter the Krebs cycle (α-ketoglutaric acid) were impaired, with significantly lower ATP generation in LRRK2-I1371V astrocytes. De novo glutamine synthesis via the conversion of glutamate to glutamine was also affected, indicating glutamate metabolism disorder. Our data demonstrate for the first time that the mutation in the LRRK2-I1371V allele causes significant astrocytic dysfunction with respect to Nrf2-mediated antioxidant machinery, AT -generation, and glutamate metabolism, even with comparable astrocyte yields.
Daphnetin, a Coumarin with Anticancer Potential against Human Melanoma: In Vitro Study of Its Effective Combination with Selected Cytostatic Drugs
Authors: Wróblewska-Łuczka Paula , Góralczyk Agnieszka , Łuszczki Jarogniew J.
Published: June 2023

(1) The treatment of metastatic or drug-resistant melanoma is still a significant therapeutic problem. The aim of this study was to evaluate the anticancer potential of daphnetin (7,8-dihydroxycoumarin) and its combinations with five different cytostatic drugs (mitoxantrone, docetaxel, vemurafenib, epirubicin and cisplatin). (2) The viability, proliferation and cytotoxicity of daphnetin against four human malignant melanoma cell lines were evaluated. The interactions were assessed using isobolographic analysis for the combinations of daphnetin with each of the five cytostatic drugs. (3) Daphnetin showed anticancer activity against malignant melanoma, with IC50 values ranging from 40.48 ± 10.90 µM to 183.97 ± 18.82 µM, depending on the cell line. The combination of daphnetin with either vemurafenib or epirubicin showed an antagonistic interaction. Moreover, additive interactions were observed for the combinations of daphnetin with cisplatin and docetaxel. The most desirable synergistic interactions for human melanoma metastatic cell lines were observed for the combination of daphnetin with mitoxantrone. (4) The obtained results suggest that daphnetin should not be combined with vemurafenib or epirubicin in the treatment of malignant melanoma due to the abolition of their anticancer effects. The combination of daphnetin with mitoxantrone is beneficial in the treatment of metastatic melanoma due to their synergistic interaction.
Epigenetic Changes Associated with Osteosarcoma: A Comprehensive Review
Authors: Twenhafel Luke , Moreno DiAnna , Punt Trista , Kinney Madeline , Ryznar Rebecca
Published: June 2023

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. While clinical outcomes have improved, the 5-year survival rate is only around 60% if discovered early and can require debilitating treatments, such as amputations. A better understanding of the disease could lead to better clinical outcomes for patients with osteosarcoma. One promising avenue of osteosarcoma research is in the field of epigenetics. This research investigates changes in genetic expression that occur above the genome rather than in the genetic code itself. The epigenetics of osteosarcoma is an active area of research that is still not fully understood. In a narrative review, we examine recent advances in the epigenetics of osteosarcoma by reporting biomarkers of DNA methylation, histone modifications, and non-coding RNA associated with disease progression. We also show how cancer tumor epigenetic profiles are being used to predict and improve patient outcomes. The papers in this review cover a large range of epigenetic target genes and pathways that modulate many aspects of osteosarcoma, including but not limited to metastases and chemotherapy resistance. Ultimately, this review will shed light on the recent advances in the epigenetics of osteosarcoma and illustrate the clinical benefits of this field of research.
Fundamental Characterization of Antibody Fusion-Single-Chain TNF Recombinant Proteins Directed against Costimulatory TNF Receptors Expressed by T-Lymphocytes
Authors: Nagai Hodaka , Azuma Mitsuki , Sato Ayaka , Shibui Nagito , Ogawara Sayaka , Tsutsui Yuta , Suzuki Ayano , Wakaizumi Tomomi , Ito Aya , Matsuyama Shimpei , Morita Masashi , Hikosaka Kuniishi Mari , Ishii Naoto , So Takanori
Published: June 2023

The costimulatory signal regulated by the members of the tumor necrosis factor receptor (TNFR) superfamily expressed by T cells plays essential roles for T cell responses and has emerged as a promising target for cancer immunotherapy. However, it is unclear how the difference in TNFR costimulation contributes to T cell responses. In this study, to clarify the functional significance of four different TNFRs, OX40, 4-1BB, CD27 and GITR, we prepared corresponding single-chain TNF ligand proteins (scTNFLs) connected to IgG Fc domain with beneficial characteristics, i.e., Fc−scOX40L, Fc−sc4-1BBL, Fc−scCD27L (CD70) and Fc−scGITRL. Without intentional cross-linking, these soluble Fc−scTNFL proteins bound to corresponding TNFRs induced NF-kB signaling and promoted proliferative and cytokine responses in CD4+ and CD8+ T cells with different dose-dependencies in vitro. Mice injected with one of the Fc−scTNFL proteins displayed significantly augmented delayed-type hypersensitivity responses, showing in vivo activity. The results demonstrate that each individual Fc−scTNFL protein provides a critical costimulatory signal and exhibits quantitatively distinct activity toward T cells. Our findings provide important insights into the TNFR costimulation that would be valuable for investigators conducting basic research in cancer immunology and also have implications for T cell-mediated immune regulation by designer TNFL proteins.
Comparative Study of Mechanical Performance of AlCrSiN Coating Deposited on WC-Co and cBN Hard Substrates
Authors: Liang Jing , Serra Marc , Gordon Sandra , Fernández de Ara Jonathan , Almandoz Eluxka , Llanes Luis , Jimenez-Piqué Emilio
Published: June 2023

The objective of this study is to explore and compare the mechanical response of AlCrSiN coatings deposited on two different substrates, namely, WC-Co and cBN. Nano-indentation was used to measure the hardness and elastic modulus of the coatings, and micro-indentation was used for observing the contact damage under Hertzian contact with monotonic and cyclic (fatigue) loads. Microscratch and contact damage tests were also used to evaluate the strength of adhesion between the AlCrSiN coatings and the two substrates under progressive and constant loads, respectively. The surface damages induced via different mechanical tests were observed using scanning electron microscopy (SEM). A focused ion beam (FIB) was used to produce a cross-section of the coating–substrate system in order to further detect the mode and extent of failure that was induced. The results show that the AlCrSiN coating deposited on the WC-Co substrate performed better in regard to adhesion strength and contact damage response than the same coating deposited on the cBN substrate; this is attributed to the lower plasticity of the cBN substrate as well as its less powerful adhesion to the coating.
New Trends in Uric Acid Electroanalysis
Authors: Chelmea Ligia , Badea Mihaela , Scarneciu Ioan , Moga Marius Alexandru , Dima Lorena , Restani Patrizia , Murdaca Cecilia , Ciurescu Daniel , Gaman Laura Elena
Published: June 2023

Considering the increasing incidence of hyperuricemia and oxidative stress-related diseases, quantification of uric acid has become essential. Therefore, the evolution on sensing devices being favorable, these questions are more often addressed to the field of medical researchers. As for many metabolites, (bio)sensors provide a reliable method for screening and evaluation of uric acid status. Due to the numerous categories of (bio)sensors available, choosing the appropriate one is a challenge. This study reviews the scientific information concerning the most suitable (bio)sensors for quantification of uric acid, presenting a list of sensors from the last decade, categorized by configurations and materials. In addition, this review includes a comparison of sensors according to their interference behavior and sensitivity, offering an objective perspective for identifying devices that are suitable for clinical applications.
Care When It Counts: Establishing Trauma-Sensitive Care as a Preventative Approach for 0–3-Year-Old Children Suffering from Trauma and Chronic Stress
Authors: Dierickx Serafine , Malisse Laura , Bisagno Elisa , Cadamuro Alessia , Van Haeken Sarah , Wuyts Dorien , Linde-Ozola Zane , Kandãte Annija , Morva Dorottya , Rozsa Monika , Gruber Andrea , Blom Johanna M. C. , De Fazio Laura Giovanna , Mosleh Dima Bou , Varga-Sabján Dóra , Groenen Anne
Published: June 2023

Adverse childhood experiences are an important societal concern. Children aged 0–3 are particularly vulnerable to unpredictable chronic stress due to the critical period for brain development and attachment. Trauma-sensitive care is a preventative approach to reduce the burden of stressful experiences by committing to positive relationships. Professional caregivers are ideally placed to offer trauma-sensitive care; however, earlier research reveals that the tools they need to consciously apply trauma-sensitive care principles are missing. The current study organized living labs (co-creative research method) to present trauma-sensitive care as a preventative approach aimed at children aged 0–3. Two living labs were organized in Belgium and Hungary, where professional caregivers collaborated to create a protocol that offers guidelines on how to implement trauma-sensitive care. The resulting protocol included a theoretical foundation on trauma as well as a translation of these guidelines into practical recommendations. The protocol was evaluated by incorporating it into a training intervention delivered to 100 professional caregivers from childcare organizations across four European countries. The protocol received positive feedback from participants, with results indicating a self-reported increase in knowledge, attitude and practice of trauma-sensitive care principles. We conclude that this trauma-sensitive care protocol is a promising answer to the needs of professional caregivers working with children aged 0–3.
Evaluation of the Mechanical and Corrosion Behavior of Twin Wire Arc Sprayed Ni-Al Coatings with Different Al and Mo Content
Authors: Bang Jaehui , Lee Eunkyung
Published: June 2023

In this study, the surface properties of marine structures were improved by applying a twin wire arc spray process to high-strength low alloys. The effect of Al and Mo contents in Ni-Al coatings on their mechanical and corrosion behaviors was analyzed using hardness tests, electrochemical experiments, and immersion tests. The increase in Al content resulted in the formation of oxides and intermetallic compounds, leading to a significant improvement in the mechanical properties by approximately 222 HV. Despite a fine galvanic phenomenon causing a decrease in corrosion resistance by up to 8.91%, a higher Al content demonstrated the highest corrosion resistance after high-temperature exposure, with an enhancement of approximately 20.9%, attributed to the formation of an oxide film generated by intermetallic phase transformation. However, the mechanical properties experienced a reduction of 134.3 HV. This study demonstrated a correlation between the microstructure of the coating layers that form passivation films and their respective mechanical and corrosion properties. It also revealed that the content of Al and Mo significantly affects the mechanical and corrosion behavior of Ni-Al coatings.