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Search Results (149)

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9 pages, 2659 KiB  
Article
Improved Experimental Yield of Temperature-Cycle-Induced Deracemization (TCID) with Cooling and Crystal Washing: Application of TCID for the Industrial Scale
by Jin Maeda, Pascal Cardinael, Adrian Flood and Gerard Coquerel
Crystals 2024, 14(7), 588; https://doi.org/10.3390/cryst14070588 - 27 Jun 2024
Viewed by 334
Abstract
Temperature-Cycle-Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential [...] Read more.
Temperature-Cycle-Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential Crystallization, experimental validation remains lacking. We applied TCID to (1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-one) (Cl-TAK), introducing a post-TCID cooling step to enhance yield and a washing step to augment enantiopurity. This refinement yielded an 89.8% mass yield with 99.1% enantiomeric excess in the crystal phase (c.e.e.) within 24 h on an 8.75 g scale, showcasing improved performance with insignificant process duration extension. Additionally, we explored the stochasticity of deracemization, observing the development from low initial crystal enantiomeric excesses (1–6% c.e.e0) at a 2.5 g scale. Kinetic analysis revealed that a 2% c.e.e0 effectively mitigates chiral flipping risks and induction time in our system. Our study underscores the potential for reduced initial c.e.e. to expedite deracemization and presents a straightforward method to optimize yield and purity, facilitating industrial application. Full article
(This article belongs to the Section Crystal Engineering)
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13 pages, 5522 KiB  
Article
Medical Education Escape Room Aligned with Flipped Classroom and Powered by Mobile Augmented Reality
by Panagiotis E. Antoniou, Fivos Papamalis, Eleni Dafli, Ioannis Poultourtzidis, Daniel Schwarz, Luke Woodham, Sarantis Dimitriadis, Konstantinos Tagaras, Nikolaos Kyriakidis, Panagiotis David, Maria Nikolaidou, Tamara Skříšovská, Terry Poulton and Panagiotis D. Bamidis
Electronics 2024, 13(12), 2367; https://doi.org/10.3390/electronics13122367 - 17 Jun 2024
Viewed by 491
Abstract
Medical education escape rooms are emerging as a viable technological resource for pedagogy-first, learner-centric educational activities. This work presents the evaluation results of the first flipped classroom implementation in medical education, thus utilizing a mobile-driven augmented reality (AR) escape room. A total of [...] Read more.
Medical education escape rooms are emerging as a viable technological resource for pedagogy-first, learner-centric educational activities. This work presents the evaluation results of the first flipped classroom implementation in medical education, thus utilizing a mobile-driven augmented reality (AR) escape room. A total of 21 first-year medical students attended a flipped classroom educational activity that aimed to acclimate the students with the workflows of basic life support. Knowledge acquisition and user perceptions were evaluated. Knowledge acquisition was evaluated with an ad hoc relevant instrument at three timepoints: (a) baseline at recruitment, (b) preclass after students had prepared for the episode, and (c) after class. Learner perceptions about the activity and the AR escape room were recorded at the activity’s end using a previously designed evaluation instrument. The results demonstrated sufficient knowledge acquisition only after completing the whole educational activity, while learners found the experience interesting, and the AR escape room challenging, thus reflecting an activity that was well formulated in structure and content. The challenges identified were the limited out of class collaboration capacity of the digital application and the highly gamified approach that at points counteracted the educational scope of the activity. Overall, these positive initial results demonstrate the potential of collaborative, escape based, activities for self-directed, learner-centric medical education. Full article
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18 pages, 951 KiB  
Article
A Ciphertext Reduction Scheme for Garbling an S-Box in an AES Circuit with Minimal Online Time
by Xu Yan, Bin Lian, Yunhao Yang, Xiaotie Wang, Jialin Cui, Xianghong Zhao, Fuqun Wang and Kefei Chen
Symmetry 2024, 16(6), 664; https://doi.org/10.3390/sym16060664 - 28 May 2024
Viewed by 487
Abstract
The secure computation of symmetric encryption schemes using Yao’s garbled circuits, such as AES, allows two parties, where one holds a plaintext block m and the other holds a key k, to compute Enc(k,m) without [...] Read more.
The secure computation of symmetric encryption schemes using Yao’s garbled circuits, such as AES, allows two parties, where one holds a plaintext block m and the other holds a key k, to compute Enc(k,m) without leaking m and k to one another. Due to its wide application prospects, secure AES computation has received much attention. However, the evaluation of AES circuits using Yao’s garbled circuits incurs substantial communication overhead. To further improve its efficiency, this paper, upon observing the special structures of AES circuits and the symmetries of an S-box, proposes a novel ciphertext reduction scheme for garbling an S-box in the last SubBytes step. Unlike the idea of traditional Yao’s garbled circuits, where the circuit generator uses the input wire labels to encrypt the corresponding output wire labels, our garbling scheme uses the input wire labels of an S-box to encrypt the corresponding “flip bit strings”. This approach leads to a significant performance improvement in our garbling scheme, which necessitates only 28 ciphertexts to garble an S-box and a single invocation of a cryptographic primitive for decryption compared to the best result in previous work that requires 8×28 ciphertexts to garble an S-box and multiple invocations of a cryptographic primitive for decryption. Crucially, the proposed scheme provides a new idea to improve the performance of Yao’s garbled circuits. We analyze the security of the proposed scheme in the semi-honest model and experimentally verify its efficiency. Full article
(This article belongs to the Special Issue New Advances in Symmetric Cryptography)
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15 pages, 6220 KiB  
Article
Assessing Tensile Strength and Electrical Conductivity of Friction Stir-Welded Joints of Copper and Aluminum Alloys
by Elizabeth Hoyos, María Camila Serna, Yesid Montoya and Jorge Hernán Córdoba
Metals 2024, 14(6), 631; https://doi.org/10.3390/met14060631 - 26 May 2024
Viewed by 614
Abstract
Dissimilar aluminum joints have widespread applications across various industries, including the electronics and automotive sectors, owing to their unique combination of advantages, including reduced density and enhanced mechanical properties. These characteristics make them an innovative solution for multi-material processing challenges presented in the [...] Read more.
Dissimilar aluminum joints have widespread applications across various industries, including the electronics and automotive sectors, owing to their unique combination of advantages, including reduced density and enhanced mechanical properties. These characteristics make them an innovative solution for multi-material processing challenges presented in the engineering industry. This article focuses on Friction Stir-Welded butt joints made using a weld–flip–weld approach between aluminum AA6061-T6 and pure copper C11000, exploring the effects of varying rotational speeds (1000, 1200, and 1400 RPM), offsets (0 and 1 mm) in the joint soundness, mechanical strength, and electrical conductivity. The welds were evaluated using non-destructive testing with phased-array ultrasound and tensile testing. Additionally, the electrical conductivity was measured to assess their response to electrical currents. The findings reveal a significant correlation between joint efficiency and electrical conductivity, with the highest values corresponding to a weld executed with a rotational speed of 1400 rpm, traverse speed of 40 mm/min, and 1 mm offset towards the aluminum, achieving the highest joint efficiency, reaching a joint efficiency of approximately 75% and 82.42% of the IACS for electrical conductivity. Full article
(This article belongs to the Special Issue Advances in Friction Stir Welding of Alloys and Metals)
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13 pages, 1370 KiB  
Article
Exploring Resistant Sources of Chickpea against Fusarium oxysporum f. sp. ciceris in Dryland Areas
by Hamid Hatami Maleki, Hamid Reza Pouralibaba, Roghayeh Ghiasi, Farshid Mahmodi, Naser Sabaghnia, Soheila Samadi, Hossein Zeinalzadeh-Tabrizi, Younes Rezaee Danesh, Beatrice Farda and Marika Pellegrini
Agriculture 2024, 14(6), 824; https://doi.org/10.3390/agriculture14060824 - 24 May 2024
Viewed by 668
Abstract
Fusarium wilt is a fungal disease that has a significant impact on chickpeas worldwide. This study examined the response of 58 chickpea genotypes to Fusarium wilt. The experiment was conducted over two growing seasons at the Sararoud and Maragheh research stations at the [...] Read more.
Fusarium wilt is a fungal disease that has a significant impact on chickpeas worldwide. This study examined the response of 58 chickpea genotypes to Fusarium wilt. The experiment was conducted over two growing seasons at the Sararoud and Maragheh research stations at the Drylands Agricultural Research Institute of Iran. Genotype resistance was screened through wilt incidence records and nonparametric stability statistic evaluation. The identified resistant genotypes were then evaluated in the greenhouse for their response to four isolates of Fusarium oxysporum f. sp. ciceris (races 1/BC, 2, 4, and 6). Out of 58 genotypes, 32 exhibited moderate resistance, while 24 showed strong resistance abilities. Under warmer conditions, disease severity was higher, with scores at the Sararoud location being higher than those at the Maragheh location. Of the total genotypes across all locations and years, 41.4% were resistant, 55.17% were moderately resistant, 1.72% were susceptible, and 1.72% were highly susceptible. The nonparametric stability measures S(1), S(2), and S(3) identified FLIP 05-42C and FLIP 05-43C as stable and resistant genotypes. The study found that Azad/Hashem K3 was stable based on the non-parametric stability measure S(6). Other resistant genotypes were identified using stability parameters NP(1), NP(3), and NP(4), while FLIP 05-104C was identified by NP(2). The genotypes selected by nonparametric stability parameters showed resistance against at least two Fusarium oxysporum f. sp. ciceris races. The screening method and nonparametric stability statistics used in this study were effective in identifying sources of resistance to Fusarium oxysporum f. sp. ciceris. Full article
(This article belongs to the Section Crop Protection, Diseases, Pests and Weeds)
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21 pages, 4123 KiB  
Article
Design and Modeling of a Terahertz Transceiver for Intra- and Inter-Chip Communications in Wireless Network-on-Chip Architectures
by Biswash Paudel, Xue Jun Li and Boon-Chong Seet
Sensors 2024, 24(10), 3220; https://doi.org/10.3390/s24103220 - 18 May 2024
Viewed by 650
Abstract
This paper addresses the increasing demand for computing power and the challenges associated with adding more core units to a computer processor. It explores the utilization of System-on-Chip (SoC) technology, which integrates Terahertz (THz) wave communication capabilities for intra- and inter-chip communication, using [...] Read more.
This paper addresses the increasing demand for computing power and the challenges associated with adding more core units to a computer processor. It explores the utilization of System-on-Chip (SoC) technology, which integrates Terahertz (THz) wave communication capabilities for intra- and inter-chip communication, using the concept of Wireless Network-on-Chips (WNoCs). Various types of network topologies are discussed, along with the disadvantages of wired networks. We explore the idea of applying wireless connections among cores and across the chip. Additionally, we describe the WNoC architecture, the flip-chip package, and the THz antenna. Electromagnetic fields are analyzed using a full-wave simulation software, Ansys High Frequency Structure Simulator (HFSS). The simulation is conducted with dipole and zigzag antennas communicating within the chip at resonant frequencies of 446 GHz and 462.5 GHz, with transmission coefficients of around −28 dB and −33 to −41 dB, respectively. Transmission coefficient characterization, path loss analysis, a study of electric field distribution, and a basic link budget for transmission are provided. Furthermore, the feasibility of calculated transmission power is validated in cases of high insertion loss, ensuring that the achieved energy expenditure is less than 1 pJ/bit. Finally, employing a similar setup, we study intra-chip communication using the same antennas. Simulation results indicate that the zigzag antenna exhibits a higher electric field magnitude compared with the dipole antenna across the simulated chip structure. We conclude that transmission occurs through reflection from the ground plane of a printed circuit board (PCB), as evidenced by the electric field distribution. Full article
(This article belongs to the Special Issue Integrated Sensing and Communication)
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13 pages, 602 KiB  
Article
Proposal for a Flipped Classroom Program with Massive Open Online Courses to Improve Access to Information and Information Literacy in Primary School Teachers
by Ana Lendínez Turón, José Manuel Ortiz Marcos, Oswaldo Lorenzo Quiles and Fiorela Anaí Fernández-Otoya
Societies 2024, 14(5), 68; https://doi.org/10.3390/soc14050068 - 15 May 2024
Viewed by 944
Abstract
The objective of this study was to propose a teacher training program based on the flipped classroom model with MOOCs to strengthen access to information and information literacy among primary education teachers in the Lambayeque region of Peru. The non-experimental design was assumed [...] Read more.
The objective of this study was to propose a teacher training program based on the flipped classroom model with MOOCs to strengthen access to information and information literacy among primary education teachers in the Lambayeque region of Peru. The non-experimental design was assumed with a quantitative approach and a propositional, descriptive type. A diagnosis was made using a questionnaire given to 917 primary school teachers. It was discovered that nearly all of the items in the questionnaire revealed a deficiency in the ability to navigate, search, and filter information, data, and digital content; the highest percentages were at the Basic level, with the exception of the item expressing information needs in an organized manner, which was at the Advanced C2 level. The lowest percentage was at the Advanced C1 level, and the majority of the lower percentages were at the Advanced level. In addition, there are competency deficiencies in the evaluation of information, data, and digital content of nearly all the items: the highest percentages were at the Basic level, with the exception of the item involving the processing of information, data, and digital content, where 26.4% were at the Intermediate B1 level and just 2.8% managed to be at the highest level, which is Advanced C2. Furthermore, when it came to storage and retrieval of information, data, and digital content competency, all the high percentages were at the Basic level, and all the low percentages were at the highest level, that is, Advanced. These findings helped us to understand that teachers have only a basic knowledge of information literacy and information competency. As a result, it is necessary to advocate for a teacher training program based on the flipped classroom model with MOOCs. This idea was supported by the opinions of five experts, who stated that its implementation would enable primary teachers of Regular Basic Education in the region of Lambayeque (Peru) to develop their access to information and information literacy competency area. Full article
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16 pages, 3595 KiB  
Article
Characterisation of PVL-Positive Staphylococcus argenteus from the United Arab Emirates
by Stefan Monecke, Sindy Burgold-Voigt, Sascha D. Braun, Celia Diezel, Elisabeth M. Liebler-Tenorio, Elke Müller, Rania Nassar, Martin Reinicke, Annett Reissig, Abiola Senok and Ralf Ehricht
Antibiotics 2024, 13(5), 401; https://doi.org/10.3390/antibiotics13050401 - 27 Apr 2024
Viewed by 1113
Abstract
Staphylococcus argenteus is a recently described staphylococcal species that is related to Staphylococcus aureus but lacks the staphyloxanthin operon. It is able to acquire both resistance markers such as the SCCmec elements and mobile genetic elements carrying virulence-associated genes from S. aureus [...] Read more.
Staphylococcus argenteus is a recently described staphylococcal species that is related to Staphylococcus aureus but lacks the staphyloxanthin operon. It is able to acquire both resistance markers such as the SCCmec elements and mobile genetic elements carrying virulence-associated genes from S. aureus. This includes those encoding the Panton–Valentine leukocidin (PVL), which is associated mainly with severe and/or recurrent staphylococcal skin and soft tissue infections. Here, we describe the genome sequences of two PVL-positive, mecA-negative S. argenteus sequence type (ST) 2250 isolates from the United Arab Emirates in detail. The isolates were found in a dental clinic in the United Arab Emirates (UAE). Both were sequenced using Oxford Nanopore Technology (ONT). This demonstrated the presence of temperate bacteriophages in the staphylococcal genomes, including a PVL prophage. It was essentially identical to the published sequence of phiSa2wa_st78 (GenBank NC_055048), a PVL phage from an Australian S. aureus clonal complex (CC) 88 isolate. Besides the PVL prophage, one isolate carried another prophage and the second isolate carried two additional prophages, whereby the region between these two prophages was inverted. This “flipped” region comprised about 1,083,000 bp, or more than a third of the strain’s genome, and it included the PVL prophage. Prophages were induced by Mitomycin C treatment and subjected to transmission electron microscopy (TEM). This yielded, in accordance to the sequencing results, one or, respectively, two distinct populations of icosahedral phages. It also showed prolate phages which presumptively might be identified as the PVL phage. This observation highlights the significance bacteriophages have as agents of horizontal gene transfer as well as the need for monitoring emerging staphylococcal strains, especially in cosmopolitan settings such as the UAE. Full article
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24 pages, 1753 KiB  
Review
McLuhan’s Tetrad as a Tool to Interpret the Impact of Online Studio Education on Design Studio Pedagogy
by Mehmet Sarper Takkeci and Arzu Erdem
Trends High. Educ. 2024, 3(2), 273-296; https://doi.org/10.3390/higheredu3020017 - 22 Apr 2024
Viewed by 1077
Abstract
The COVID-19 pandemic has led to a surge in online studio education, which has presented a significant challenge to traditional design studio teaching methods that rely on face-to-face interactions between instructors and students. It is contended that online studio education enhances the accessibility [...] Read more.
The COVID-19 pandemic has led to a surge in online studio education, which has presented a significant challenge to traditional design studio teaching methods that rely on face-to-face interactions between instructors and students. It is contended that online studio education enhances the accessibility of design studio pedagogy, making it possible for students to learn from anywhere in the world. However, it also challenges the development of tactile skills, which are crucial in design education. Additionally, online studio education can render certain aspects of traditional design studio pedagogy obsolete, while bringing back elements of design history and theory that may have been overlooked in traditional studio teaching. It can also be argued that online studio education has the potential to reverse the traditional power dynamics between instructors and students, resulting in more democratic and collaborative forms of learning that can empower students. As the literature on the effects of online studio education is growing, there is a need to understand how the shift from the material space and its affordances to an online environment affects the core components of an architectural design studio. To understand the effects of this new medium, this research employed Marshall McLuhan’s tetradic approach, a hermeneutic tool to perform a critical interpretation of any medium by examining four simultaneous effects: how it enhances a human sense, what it makes obsolete, what forgotten aspect it retrieves, and how it flips into its opposite at its extremes. A literature review was conducted to analyze the effects of online studios from a tetradic framework and identify the major discussions of the impact of online studio education. The methodology involves a two-part literature review. This study specifically focused on peer-reviewed, empirical research published after 2020, and the authors used search terms related to online architectural studios during the pandemic. The process identified 176 records of peer-reviewed empirical studies for further analysis and 20 papers were read and included in the review, defining repeating topics/themes and organized under four categories pertaining to the founding archetypes of an architectural design studio: (a) setting and communication, (b) actors, (c) outputs, and (d) dynamics. This process was followed by organizing the findings and interpreting them within the tetradic framework to develop a comprehensive understanding of the consequences of the online design studio. Overall, this research aims to provide a detailed and nuanced analysis of the impact of online studio education on design studio pedagogy, conceptualizing McLuhan’s tetrad as a basis for the analysis, and therefore aiming to enrich our understanding of the post-COVID-19 era of learning architecture by examining the dramatic change in the medium and its effects. Full article
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18 pages, 11227 KiB  
Article
A Method for Stabilizing the Vibration Amplitude of a Flip-Flow Vibrating Screen Using Piecewise Linear Springs
by Dongdong Lin, Xinwen Wang, Ningning Xu, Weiran Zuo and Zhian Liang
Minerals 2024, 14(4), 406; https://doi.org/10.3390/min14040406 - 16 Apr 2024
Viewed by 738
Abstract
The flip-flow vibrating screen (FFVS) is a novel multi-body screening equipment that utilizes vibrations to classify bulk materials in the field of screening machinery. The relative amplitude of FFVSs determines the tension and ejection intensity of elastic flip-flow screen panels, which is a [...] Read more.
The flip-flow vibrating screen (FFVS) is a novel multi-body screening equipment that utilizes vibrations to classify bulk materials in the field of screening machinery. The relative amplitude of FFVSs determines the tension and ejection intensity of elastic flip-flow screen panels, which is a critical operating parameter affecting the screening performance. However, FFVSs generally suffer from large variations of relative amplitude caused by the loading of materials and the changes in shear spring stiffness (the temperature changes of the shear springs lead to their stiffness changes), which significantly reduce the screening efficiency and lifespan of FFVSs. To address this problem, this paper proposes a nonlinear stiffness-based method for stabilizing the vibration amplitude of FFVSs using piecewise linear springs. By introducing these springs between the two frames, the sensitivity of the relative amplitude to shear spring stiffness is reduced, thereby achieving the stabilization of the relative amplitude of FFVSs. In this study, the variations of the vibration amplitude of the FFVS due to the loading of materials and the changes in shear spring stiffness were first demonstrated in a reasonable operating frequency range. Then the reasonable operating frequency range and dynamics of the resultant nonlinear flip-flow vibrating screen (NFFVS) with piecewise linear springs were investigated using the harmonic balance method (HBM) and the Runge–Kutta numerical method. The operating frequency region for the NFFVS lies between the critical frequency ωcs and the frequency ωlb corresponding to the saddle-node bifurcation point. Finally, a test rig was designed to validate the theoretical predictions. Theoretical and experimental results demonstrate that piecewise linear springs can effectively stabilize the relative amplitude of the FFVS. Full article
(This article belongs to the Section Mineral Processing and Extractive Metallurgy)
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19 pages, 4148 KiB  
Article
A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1
by Christina Sathyanathan Vijayaraghavan, Lakshmi Sundaram Raman, Shanmugapriya Surenderan, Harpreet Kaur, Mohanapriya Dandapani Chinambedu, Sadras Panchatcharam Thyagarajan and Mary Elizabeth Gnanambal Krishnan
Molecules 2024, 29(8), 1737; https://doi.org/10.3390/molecules29081737 - 11 Apr 2024
Viewed by 712
Abstract
The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is [...] Read more.
The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects. Full article
(This article belongs to the Section Natural Products Chemistry)
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11 pages, 1608 KiB  
Article
Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells
by Jeong Man Cho, Sojung Sun, Eunji Im, Hyunwon Yang and Tag Keun Yoo
Medicines 2024, 11(3), 7; https://doi.org/10.3390/medicines11030007 - 21 Feb 2024
Viewed by 1465
Abstract
Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on [...] Read more.
Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer. Full article
(This article belongs to the Section Cancer Biology and Anticancer Therapeutics)
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16 pages, 1148 KiB  
Article
University Students as Change Agents for Health and Sustainability: A Pilot Study on the Effects of a Teaching Kitchen-Based Planetary Health Diet Curriculum
by Nicola Rosenau, Uwe Neumann, Stacey Hamblett and Thomas Ellrott
Nutrients 2024, 16(4), 521; https://doi.org/10.3390/nu16040521 - 13 Feb 2024
Cited by 1 | Viewed by 2217
Abstract
Global dietary habits are one of the main drivers of climate change. At the same time, they contribute to 11 million premature deaths every year. This raises the question of how the urgently needed transformation of food systems can be realized. Regardless of [...] Read more.
Global dietary habits are one of the main drivers of climate change. At the same time, they contribute to 11 million premature deaths every year. This raises the question of how the urgently needed transformation of food systems can be realized. Regardless of their degree paths, all university students, in their role as potential future experts and leaders in their fields, can serve as important change agents in society. In this paper, we (a) introduce a university curriculum in a teaching kitchen setting that is based on the planetary health diet (PHD) of the EAT-Lancet Commission, (b) investigate its feasibility, and (c) analyze its effects on the planetary health diet literacy of a pilot cohort of university students enrolled in various degree programs. We developed seven flipped classroom teaching kitchen sessions based on social cognitive theory (SCT), each consisting of a one-hour seminar with student presentations on various nutrition- and sustainability-related key topics, followed by corresponding two-hour hands-on cooking classes. To assess feasibility, specific questions from the official teaching evaluation of the University of Göttingen were analyzed. Changes in self-assessed planetary health diet literacy were measured using a pre- and post-survey. During the pilot phase, 26 students successfully completed the course. A total of 25 participants responded to the teaching evaluation and expressed high satisfaction with the course, the learning outcomes, and the level of demand. A total of 26 participants completed the pre- and post-survey. At the post-intervention, the students rated their planetary health diet literacy as 21 to 98% higher than before their course participation. The findings of this pilot study indicate that the curriculum was well-received and feasible with the target group, and they demonstrate that the course participation increased the university students’ self-assessed ability to disseminate strategies for more sustainable and healthy diets. Through replication at other universities worldwide, the teaching kitchen-based planetary health diet curriculum might foster a social shift towards healthier and more climate-friendly food systems. Full article
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17 pages, 4517 KiB  
Article
Bortezomib in Combination with Physachenolide C Reduces the Tumorigenic Properties of KRASmut/P53mut Lung Cancer Cells by Inhibiting c-FLIP
by Thanigaivelan Kanagasabai, Zerick Dunbar, Salvador González Ochoa, Tonie Farris, Sivanesan Dhandayuthapani, E. M. Kithsiri Wijeratne, A. A. Leslie Gunatilaka and Anil Shanker
Cancers 2024, 16(3), 670; https://doi.org/10.3390/cancers16030670 - 4 Feb 2024
Viewed by 1372
Abstract
Background: Defects in apoptosis regulation are one of the classical features of cancer cells, often associated with more aggressiveness and failure to therapeutic options. We investigated the combinatorial antitumor effects of a natural product, physachenolide C (PCC) and bortezomib, in KRASmut/P53 [...] Read more.
Background: Defects in apoptosis regulation are one of the classical features of cancer cells, often associated with more aggressiveness and failure to therapeutic options. We investigated the combinatorial antitumor effects of a natural product, physachenolide C (PCC) and bortezomib, in KRASmut/P53mut lung cancer cells and xenograft mice models. Methods: The in vitro anticancer effects of the bortezomib and PCC combination were investigated using cell viability, migration, and invasion assays in 344SQ, H23, and H358 cell lines. Furthermore, the effects of combination treatment on the critical parameters of cellular metabolism, including extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation based on the oxygen consumption rate of cancer cells were assessed using Seahorse assay. Finally, the antitumor effect of the bortezomib (1 mg/kg) and PCC (10 mg/kg) combination was evaluated using xenograft mice models. Results: Our data showed that the bortezomib–PCC combination was more effective in reducing the viability of lung cancer cells in comparison with the individual treatments. Similarly, the combination treatment showed a significant inhibition of cell migration and invasion of cancer cells. Additionally, the key anti-apoptotic protein c-FLIP was significantly inhibited along with a substantial reduction in the key parameters of cellular metabolism in cancer cells. Notably, the bortezomib or PCC inhibited the tumor growth compared to the control group, the tumor growth inhibition was much more effective when bortezomib was combined with PCC in tumor xenograft mice models. Conclusion: These findings demonstrate that PCC sensitizes cancer cells to bortezomib, potentially improving the antitumor effects against KRASmut/P53mut lung cancer cells, with an enhanced efficacy of combination treatments without causing significant side effects. Full article
(This article belongs to the Section Molecular Cancer Biology)
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19 pages, 4810 KiB  
Article
The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells
by Katherine Yaacoub, Rémy Pedeux, Pierre Lafite, Ulrich Jarry, Samia Aci-Sèche, Pascal Bonnet, Richard Daniellou and Thierry Guillaudeux
Curr. Issues Mol. Biol. 2024, 46(1), 710-728; https://doi.org/10.3390/cimb46010046 - 12 Jan 2024
Cited by 1 | Viewed by 2556
Abstract
The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following death receptors’ (DRs) activation via the ligands of the TNF-R [...] Read more.
The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following death receptors’ (DRs) activation via the ligands of the TNF-R family. As a consequence, the extrinsic apoptotic signaling pathway involving DRs is inhibited. The inhibition of c-FLIP activity in tumor cells might enhance DR-mediated apoptosis and overcome immune and anticancer drug resistance. Based on an in silico approach, the aim of this work was to identify new small inhibitory molecules able to bind selectively to c-FLIP and block its anti-apoptotic activity. Using a homology 3D model of c-FLIP, an in silico screening of 1880 compounds from the NCI database (National Cancer Institute) was performed. Nine molecules were selected for in vitro assays, based on their binding affinity to c-FLIP and their high selectivity compared to caspase-8. These molecules selectively bind to the Death Effector Domain 2 (DED2) of c-FLIP. We have tested in vitro the inhibitory effect of these nine molecules using the human lung cancer cell line H1703, overexpressing c-FLIP. Our results showed that six of these newly identified compounds efficiently prevent FADD/c-FLIP interactions in a molecular pull-down assay, as well as in a DISC immunoprecipitation assay. The overexpression of c-FLIP in H1703 prevents TRAIL-mediated apoptosis; however, a combination of TRAIL with these selected molecules significantly restored TRAIL-induced cell death by rescuing caspase cleavage and activation. Altogether, our findings indicate that new inhibitory chemical molecules efficiently prevent c-FLIP recruitment into the DISC complex, thus restoring the caspase-8-dependent apoptotic cascade. These results pave the way to design new c-FLIP inhibitory molecules that may serve as anticancer agents in tumors overexpressing c-FLIP. Full article
(This article belongs to the Section Molecular Medicine)
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