bluuebunny/crossref_metadata_2025 huggingface dataset:
Teachers in the Loop: Integrating Computational Thinking and Mathematics to Build Early Place Value Understanding
Authors: Dahshan Mai , Galanti Terrie
Published: February 2024

With increasing attention on the potential overlap between computational thinking (CT) and mathematical reasoning, STEM education researchers seek to understand how integrating CT and mathematics can deepen student learning across disciplines. Although there are various professional development programs that introduce teachers to CT concepts and strategies for curriculum integration, limited research exists on how teachers might apply this knowledge to create math + CT activities for use with their students. Additionally, the majority of research on CT integration through programming has focused on upper elementary grades, leaving the early grades (K-2) relatively unexplored. This qualitative exploratory study aims to examine how teachers in a graduate STEM education program collaborated with university STEM faculty to explore and critique a set of integrated math + CT block-based programming activities designed to build place value conceptual understanding. In-service elementary teachers enrolled in an online graduate CT course for educators (n = 13) explored these activities as learners and drew on their experiences as classroom teachers to offer feedback for program redesign. A sequence of deductive pattern coding and inductive holistic coding of course transcripts, collaborative problem-solving slides, and individual teacher reflections provided insights into how teachers were able to establish connections between their mathematical knowledge related to teaching place value and their emerging understanding of CT concepts, such as abstraction, algorithms, decomposition, and debugging. Implications for the design of professional development for elementary teachers on integrating CT and mathematics are offered.
Technology-Mediated Hindustani Dhrupad Music Education: An Ethnographic Contribution to the 4E Cognition Perspective
Authors: Paschalidou Stella
Published: February 2024

Embodiment lies at the core of music cognition, prompting recent pedagogical shifts towards a multi-sensory, whole-body approach. However, the education of oral music genres that rely exclusively on direct teacher–disciple transmission through live demonstration and imitation is now undergoing a transformation by rapidly adapting to technology-mediated platforms. This paper examines challenges in embodied facets of video-mediated synchronous distance Hindustani music pedagogy. For this, it takes an ethnomusicological stance and showcases a thematic analysis of interviews featuring Dhrupad music practitioners. The analysis is driven and organized by the 4E Cognition principles, which stress the intimate relationship between body, mind, and environment. Findings indicate that while this adaptation aims to make music content more widely accessible, it comes at the cost of reducing opportunities for multi-modal engagement and interaction among participants. Results reveal limitations in transmitting non-verbal, embodied, multi-sensory cues, along with visual and acoustic disruptions of a sense of shared spatial and physical context, that hinder effective interaction and a sense of immersion, elements that are deemed vital in music education. They prompt concerns about the suitability of conventional videoconferencing platforms and offer key insights for the development of alternative technologies that can better assist embodied demands of the pedagogical practices involved.
Independent Semantic and Syntactic Representations in L2 Mandarin Learners: Evidence from Structural Priming
Authors: Getty Douglas J. , Wei Xiang , Chen Lin
Published: February 2024

Structural representations in English have been shown to be quite abstract, with structural information being represented independently from semantic information. Mandarin has a relatively sparse marking of syntactic information, with no inflections for case, number, or tense. Given this syntactic sparsity, Huang et al. (2016) hypothesized that, distinct from English-language findings, Mandarin learners may have shared syntactic and semantic representations, such that semantic information can guide structure building. We examined this question in L2 Mandarin learners using a structural priming paradigm that required reading Mandarin primes. We found that L2 Mandarin learners exhibit within-language structural priming, and this effect is independent of semantic information. These findings have two implications: (1) this represents the first demonstration of within-language L2 Mandarin structural priming; (2) L2 learners can develop syntactic representations independent of semantic representations, even when the target L2 language lacks rich marking of syntactic information.
University Teaching as a Site for Professional Learning of Teacher Educators: The Role of Collaborative Inquiry and Reflection within a Professional Learning Community
Authors: Avgitidou Sofia , Karadimitriou Konstantinos , Ampartzaki Maria , Sidiropoulou Christina , Kampeza Maria
Published: February 2024

While initial teacher education (ITE) has been acknowledged as an important process for improving the quality of education by preparing future teachers, less attention has been paid to the support of the continuous professional learning of teacher educators (TEs). This study reports on the supporting processes and tools for a collaborative inquiry-based systematic reflection of five TEs and the effects of their use in constructing professional knowledge about ITE. The reflective written reports and reflective discussions of the TEs are thematically analysed to show the focus of inquiry, the links among inquiry, reflection, and action, as well as the contributing role of collaboration within a professional learning community (PLC). The results show that the TE inquiry was a continuous process of exploring the beliefs, understandings, and participation of pre-service teachers (PSTs) during teaching; the impact of the teaching context on TE actions and decisions; and the ways in which their collaboration enhanced professional learning. The inquiry results informed the reflections and practice design of TEs. Guiding questions, sustained interactions among the PLC members, and support from a facilitator created opportunities for the collaborative construction of the professional learning of TEs. This article provides TEs or/and facilitators of PLCs in teacher education with a methodology for supporting professional knowledge through collaborative inquiry and reflection.
Inclusive Special Needs Education and Happiness of Students with Physical Disabilities in Saudi Arabia: The Role of School Satisfaction and Self-Concept
Authors: Ragmoun Wided , Alfalih Abdulaziz Abdulmohsen
Published: February 2024

This research aims to discover how inclusive education practices can determine the happiness and school satisfaction of students with physical disabilities through the development of self-concept. To achieve the objective of this study, quantitative research was used by administering a questionnaire to 403 students with special needs in secondary and high school in Saudi Arabia. The collected data were analyzed according to structural equation modeling. Our findings support the considerable agreement on the importance of inclusive special needs education for the happiness of physically disabled students. A total mediating effect of self-concept between ISNE and school satisfaction is also confirmed, which shows the great importance of the psychological dimension in special education. These results can orient and assist school managers in defining an appropriate educational environment for students with special needs. They can provide specific directives for raising the happiness and the quality of life of such students, making them more productive and socially active. Following this research, a new school framework can be drawn to protect, assist, and change the self-concept of students with physical special needs to shift the perspective of disability from an obstacle to overcome to an opportunity to exploit.
Enhanced Succinic Acid Production and Electronic Utilization Efficiency by Actinobacillus succinogenes 130Z in an ORP-Controlled Microbial Electrolysis Cell System
Authors: Peng Jieyi , Zhao Shuo , Li Ying , Wang Zhen , Chen Li
Published: February 2024

Microbial electrochemical systems have shown great value as a means of enhancing the efficiency of fermentation reactions, but at present, there is no reliable means to balance the extracellular electron supply and corresponding intracellular demands in these systems. The current work describes the unique use of an oxidation–reduction-potential (ORP)-level-controlled microbial electrolysis cell (MEC) system to successfully balance the extracellular electron supply and succinic acid fermentation via A. succinogenes (130Z). The ORP-controlled MEC system with neutral red (NR) yielded a significant increase in succinic acid production (17.21%). The utilization of NR in this MEC system improved the ORP regulatory sensitivity. The optimal approach to the ORP level control was the use of a −400 mV high-voltage electric pulse-based strategy, which increased the yield of succinic acid by 13.08% compared to the control group, and reduced the energy consumption to 52.29% compared to the potentiostatic method. When compared to the −1 V constant potential MEC system, the high-voltage electric pulse-based ORP strategy for the MEC system control provided sufficient electrons to this system while using less electricity (11.96%) and producing 12.48% (74.43 g/L) more succinic acid during fed-batch fermentation. The electronic utilization efficiency of the ORP-controlled MEC system was 192.02%, which was 15.19 times that of the potentiostatic system. The electronic utilization efficiency is significantly increased in the ORP-controlled MEC system. Succinic acid production is ensured by a high-voltage electric pulse-based method, while the influence on cell growth and power consumption are minimized. Fed-batch fermentation with the high-voltage electric pulse-based ORP strategy for MEC system control is noted to be ideal to achieve a further increase in succinic acid concentration and electronic utilization efficiency.
Optimization of Fermentation Conditions for 2,3,5-Trimethylpyrazine Produced by Bacillus amyloliquefaciens from Daqu
Authors: Liu Xun , Yang Weijie , Gu Hongyi , Bughio Ayaz Ali , Liu Jun
Published: February 2024

2,3,5-trimethylpyrazine (TMP), as a volatile heterocyclic nitrogen compound, has a wide range of applications. To explore an efficient and environmentally friendly way to produce TMP, Bacillus strains were isolated from Daqu using traditional separation and purification methods. The fermentation products were detected by gas chromatography–mass spectrometry (GC-MS), and the species relationship of strains was analyzed by morphological and phylogenetic tree construction. Single factors were selected to optimize the fermentation process of TMP production, and a Box–Behnken design was used for response surface testing. The LC-6 strain isolated from Daqu was Bacillus amyloliquefaciens, and its fermentation products contained TMP, with a relatively high value of 0.071 ± 0.011 mg/g, indicating that the LC-6 strain was a potentially valuable TMP-producing bacterium. The results of single-factor testing showed that temperature, bottle capacity, and water addition significantly affected TMP production. Box–Behnken design and response surface analysis revealed that the order of influence on TMP yield was as follows: water addition > temperature > bottle capacity. Response surface optimization results showed that the optimal parameters for wheat medium fermentation were temperature 37 °C, bottle capacity 100 g/250 mL, and water addition 39 mL. Under these fermentation conditions, the average production of TMP was 0.446 ± 0.052 mg/g, which was 0.375 mg/g higher than that obtained before optimization. Compared with the previous period, the production of TMP indeed increased, providing a basis for further research on the solid-state fermentation process of TMP synthesis.
Repairing of One-Way Solid Slab Exposed to Thermal Shock Using CFRP: Experimental and Analytical Study
Authors: Shhabat Mousa , Ashteyat Ahmed , Abdel-Jaber Mu’tasim
Published: February 2024

This research was conducted to investigate, experimentally, theoretically, and numerically, the use of CFRP materials for repairing a reinforced concrete one-way solid slab exposed to thermal shock. Nine slabs, measuring 1800 mm in length, 500 mm in width, and 100 mm in depth, were cast. Seven of these slabs underwent thermal shock at a temperature of 600 °C, rapidly cooled by immersion in water for 15 min. Three primary parameters were examined: the type of CFRP (rope, strip, and sheet), spacing (100 and 200 mm), and the number of sheet layers (one and two). The experimental results revealed a significant decrease of approximately 45.4% in the compressive strength of the concrete after exposure to thermal shock. The thermally shocked RC slab showed a reduction in ultimate capacity by 15.4% and 38.5% in stiffness compared to the control slab. The results underscored the efficacy of CFRP materials, with all repair configurations exhibiting a substantial increase in maximum load capacity and stiffness. Capacity enhancement ranged from 23.7% to 53.4%, while stiffness improvement ranged from 27.6% to 57.1%. Notably, all repair configurations effectively minimized the maximum deflection. This reduction in deflection ranged from 5.2% to 26% compared to the control slab. Numerical results demonstrated strong concurrence with experimental results for both capacity and deflection. The enhancement in capacity ranged from 0.7% to 10.4%, while deflection decreased within a range from 0.95% to 14.16% compared to experimental results.
Magnetically Suspended Control Sensitive Gyroscope Rotor High-Precision Deflection Decoupling Method using Quantum Neural Network and Fractional-Order Terminal Sliding Mode Control
Authors: Ren Yuan , Li Lei , Wang Weijie , Wang Lifen , Pang Weikun
Published: February 2024

To achieve high-precision deflection control of a Magnetically Suspended Control and Sensitive Gyroscope rotor under high dynamic conditions, a deflection decoupling method using Quantum Radial Basis Function Neural Network and fractional-order terminal sliding mode control is proposed. The convergence speed and time complexity of the neural network controller limit the control accuracy and stability of rotor deflection under high-bandwidth conditions. To solve the problem, a quantum-computing-based structure optimization method for the Radial Basis Function Neural Network is proposed for the first time, where the input and the center of hidden layer basis function of the neural network are quantum-coded, and quantum rotation gates are designed to replace the Gaussian function. The parallel characteristic of quantum computing is utilized to reduce the time complexity and improve the convergence speed of the neural network. On top of that, in order to further address the issue of input jitter, a fractional-order terminal sliding mode controller based on the Quantum Radial Basis Function Neural Network is designed, the fractional-order differential sliding mode surface and the fractional-order convergence law are proposed to reduce the input jitter and achieve finite-time convergence of the controller, and the Quantum Radial Basis Function Neural Network is used to approximate the residual coupling and external disturbances of the system, resulting in improving the rotor deflection control accuracy. The semi-physical simulation experiments demonstrate the effectiveness and superiority of the proposed method.
Bacterial Nanocellulose Hydrogel for the Green Cleaning of Copper Stains from Marble
Authors: Sonaglia Erica , Schifano Emily , Sharbaf Mohammad , Uccelletti Daniela , Felici Anna Candida , Santarelli Maria Laura
Published: February 2024

Cultural heritage stone materials frequently experience significant discoloration induced by copper corrosion products, especially calcareous stones associated with bronze or copper statues and architectural elements. This alteration originates from the corrosion of unprotected copper, resulting in the formation of various Cu minerals and the migration of soluble ions to adjacent stone materials. Traditional cleaning methods involve mechanical, chemical, and laser techniques, which are generally time-consuming, costly, not ecological, or can possibly damage original materials. The loading of highly effective chelating agents, such as ethylenediaminetetraacetic acid (EDTA), into hydrogels has recently been exploited. However, the preference for synthetic hydrogels has been prominent until now, although they lack renewability and biodegradability and require high costs. This study explores for the first time the potential to clean copper corrosion with bacterial nanocellulose (BC) loaded with EDTA as a biologically based, sustainable, and biodegradable hydrogel. The BC hydrogel was characterised by field emission–scanning electron microscopy (FE–SEM), X-ray diffraction analysis (XRD), attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR), simultaneous thermal analysis (TG-DSC), and tensile testing. It revealed a nano-fibrous structure with high crystallinity and purity and mechanical properties suitable for cultural heritage applications. The EDTA-loaded hydrogel effectively removed copper stains from marble after 120 min of application. Micro-Raman and colorimetric analyses assessed the cleaning efficacy. The study introduces bacterial nanocellulose as a green and effective alternative for heritage conservation, aligning with sustainable methodologies in stone conservation.
Screening of Apple Cultivars for Scab Resistance in Kazakhstan
Authors: Madenova Aigul , Aitymbet Zhankeldy , Bolat Munira , Kaldybayeva Dinara , Galymbek Kanat , Kuan Angsagan , Kabylbekova Balnur , Irkitbay Azhargul , Yeszhanov Tynyshbek , Bakirov Serik , Sapakhova Zagipa
Published: February 2024

Scab, caused by Venturia inaequalis, is the most destructive fungal disease of apple worldwide. Apple scab incidence was studied in apple orchards in the south and southeast of Kazakhstan, including the Almaty, Zhambyl, and Turkestan regions, during 2022 and 2023. Disease incidence was higher in the Zhambyl region than in the Turkestan and Almaty regions in both years. The field evaluation suggested that 19 genotypes showed resistance to apple scab. Molecular screening was carried out using eight gene-specific molecular markers (AM19, CH05e03, OPL19, Hi07f02, AL07, K08, HB09, and CH02f06). The results of the molecular screening revealed that in 38 of the 45 studied cultivars, which included 11 Kazakh cultivars and 34 foreign cultivars, the Rvi (Rvi2, Rvi4, Rvi5, Rvi6, Rvi8, Rvi9, Rvi11, Rvi14, and Rvi15) resistance genes were amplified. Resistance genes such as Rvi2, Rvi4, Rvi6, and Rvi9 are still useful for breeding, but their use is recommended only in extended pyramids of multiple resistance genes. Several cultivars will be strong candidates for further breeding programs against apple scab and for the pyramiding of scab resistance genes in new cultivars.
Improvement of Drought Resistance of Osteospermum ecklonis Plants as a Physiological and Biochemical Response to Low Doses of UV-C Irradiation
Authors: Darras Anastasios I. , Kostriva Anna , Dimiza Kallirroi , Apostolou Maria , Malamas Ioannis , Kargakou Vasiliki , Kartsonas Epaminondas
Published: February 2024

Osteospermum ecklonis DC. NORL. is native to South Africa and is fully adapted to the Mediterranean climate. The aim of the study was to elucidate morphological and developmental changes in O. ecklonis plants associated with drought resistance in response to low doses of UV-C. Growth responses under three levels of drought stress (NW: normal watering, MD: moderate drought stress and SD: severe drought) were recorded. The results showed that 1 kJ m−2 UV-C significantly (p < 0.05) increased resistance to water stress without affecting growth and development or damaging photosystem II. Fresh weights of the upper parts and the root system of the irradiated plants were maintained at similar levels to those of the non-irradiated control plants. Fv/Fm values in the irradiated plants ranged from 0.73 to 0.82 depending on the stress level, while in the non-irradiated plants, the values ranged from 0.69 to 0.83. Differences between UV-C irradiated and non-irradiated plants were recorded in electrolyte leakage (EL), in malondialdehyde (MDA) and in relative water content (RWC) at all drought levels. The EL percentage of the non-irradiated plants at SD was 19.7%, while in the irradiated plants, it was 17.8%. RWC rates in the irradiated plants ranged between 60.6 and 76.4%, while in the non-irradiated plants, they ranged from 54.2 to 63.6%. Superoxide dismutase (SOD) and catalase (CAT) activities increased with UV-C irradiation, suggesting that antioxidant responses were induced and protected cell membranes from lipid peroxidation and damage. The results of the present study showed that UV-C irradiation at 1 kJ m−2 alleviated the drought symptoms of O. ecklonis by reducing oxidative stress and membrane lipid peroxidation.
Genome-Wide Identification and Expression Analysis of SWEET Gene Family in Strawberry
Authors: Tian Riru , Xu Jiayi , Xu Zichun , Li Jianuo , Li He
Published: February 2024

The Sugars Will Eventually be Exported Transporter (SWEET) is a class of bidirectional sugar transporter that is involved in critical physiological processes such as plant growth and development, and its response to biotic and abiotic stresses. Currently, there are few reports on the SWEET gene family in strawberry. In this study, we mined the SWEET gene family members in Fragaria × ananassa ‘Camarosa’ and carefully analyzed their molecular features and expression patterns. The results showed that 77 FanSWEET genes existed in the F. × ananassa ‘Camarosa’ genome, and the phylogenetic analysis classified them into four sub-groups. Analysis of gene structure, conserved structural domains, and conserved motifs showed that FanSWEETs were highly conserved during the evolutionary process. Expression profiling of the 11 FanSWEET genes revealed that three members were highly expressed in strawberry fruits, which were presumed to be involved in sugar transport during strawberry fruit ripening. In addition, based on the exogenous sugar-spraying treatment and quantitative real-time PCR analysis, we found that different members responded to different sugar treatments in different response patterns, and their functions in sugar transport need to be further explored. The present study provides a reference for further analysis of the functions of the SWEET gene in strawberry.
Phyllanthus Lignans: A Review of Biological Activity and Elicitation
Authors: Nawfetrias Winda , Devy Lukita , Esyanti Rizkita Rachmi , Faizal Ahmad
Published: February 2024

The Phyllanthus genus exhibits a broad distribution spanning across the majority of tropical and subtropical regions. Due to their ability to synthesize medicinal bioactive compounds such as lignans, they have been utilized historically in traditional medicine to treat a wide range of ailments. This review discusses the current knowledge on the potency of lignans for medicinal purposes, the benefit of lignans for plants, various lignans produced by Phyllanthus, and how lignan synthesis could be increased through biotic and abiotic elicitation. Finally, we present a set of connected hypotheses to explain how signaling crosstalk between endophytic microbes and drought stress responses regulates lignan production. Although the mechanisms of lignan synthesis in Phyllanthus are not fully explored, this review strongly supports the view that endophytic fungi and drought stress can increase lignan production in plants belonging to the genus Phyllanthus. The medicinal plant–endophyte–drought stress relationship helps to improve the lignan yield of Phyllanthus, which is crucial for human health and can be optimized under in vitro and in vivo conditions.
The Association between Functional Dyspepsia and Metabolic Syndrome—The State of the Art
Authors: Volarić Mile , Šojat Dunja , Majnarić Ljiljana Trtica , Vučić Domagoj
Published: February 2024

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain–gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.
The Relationship between Bachelor’s-Level Nursing Roles and Job Satisfaction in Nursing Homes: A Descriptive Study
Authors: Mansier-Kelderman Marijke , Lovink Marleen , Persoon Anke
Published: February 2024

The greatest shortages in the nursing discipline are expected in nursing homes. Although job satisfaction is an important factor in the retention of Bachelor’s-level nurses (BNs), little is known about the relationship between the BN roles that are performed on a daily basis and job satisfaction. A cross-sectional, descriptive, questionnaire study was conducted which was based on a convenience sample. The extent of performing seven BN roles was assessed by a self-developed questionnaire. Satisfaction was investigated at three levels: satisfaction with the BN role performance, satisfaction with the work packet (the combination of all roles performed) and satisfaction with job function (all things considered). Respondents (N = 78) were satisfied with the performance of all BN roles (range 3.71–4.42), generally satisfied with the work packet (M = 3.96; SD = 0.96) and neutral about the job function (M = 3.15; SD = 1.12). Not one single BN role correlated with job satisfaction, and the work packet (as a combination of all roles) was significantly related to job satisfaction (r = 0.551; p = 0.000). Four BN roles correlated significantly with satisfaction with the work packet, of which one was meaningful, the role of reflective Evidence-Based Practice professional (r = 0.476; p = 0.000), and three roles related less strongly: the roles of Organiser (r = 0.364; p = 0.001), Communicator (r = 0.224; p = 0.049), and Professional and Quality Enhancer (r = 0.261; p = 0.021). It is important for nurses to create interesting packets of BN roles for themselves. For nurses and care managers, it is essential to create interesting BN descriptions, with highly recognisable BN roles in the work packet, and to stimulate a work environment in order to enhance job satisfaction.
Synthetic Central Bank Digital Currencies and Systemic Liquidity Risks
Authors: Marthinsen John E. , Gordon Steven R.
Published: February 2024

The failure of major banks in 2023, such as Silicon Valley Bank (SVB), Signature Bank, First Republic Bank, and Credit Suisse, points to the continuing need for financial institutions to price liquidity risk properly and for financial systems to find alternative sources of liquidity in times of dire need. Central bank digital currencies (CBDCs), fiat-backed stablecoins (fsCOINs), and synthetic central bank digital currencies (sCBDCs) could offer improvements, but each comes with its own set of problems and conditions. Prior research reaches conflicting conclusions about the effect that each of these three financial assets has on systemic bank liquidity and fails to adequately address their net benefits relative to each other. This paper addresses these issues, including those connected to financial disintermediation, bank runs, outsourcing central bank activities, financial interoperability, cash equivalents, maturity transformation, required reserves, and changes in nations’ monetary bases. After addressing the strengths and weaknesses of fsCOINs and CBDCs, we conclude that sCBDCs provide the most significant net liquidity benefits when risks and returns are considered.
Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets
Authors: Silvestro Serena , Raffaele Ivana , Quartarone Angelo , Mazzon Emanuela
Published: February 2024

A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life and functionality. They cause two types of damage to the brain: primary and secondary. Secondary damage is particularly critical as it involves complex processes unfolding after the initial injury. These processes can lead to cell damage and death in the brain. Understanding how these processes damage the brain is crucial for finding new treatments. This review examines a wide range of literature from 2021 to 2023, focusing on biomarkers and molecular mechanisms in TBIs to pinpoint therapeutic advancements. Baseline levels of biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) in TBI, have demonstrated prognostic value for cognitive outcomes, laying the groundwork for personalized treatment strategies. In terms of pharmacological progress, the most promising approaches currently target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce a TBI’s impact and aid in neurological rehabilitation. Future research is poised to refine these therapeutic approaches, potentially revolutionizing TBI treatment.
Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers—A Systematic Review
Authors: Ciocan Răzvan , Ciocan Andra , Mihăileanu Florin , Ursu Cristina-Paula , Ursu Ștefan , Bodea Cătălin , Cordoș Ariana-Anamaria , Chiș Bogdan , Al Hajjar Nadim , Dîrzu Noemi , Dîrzu Dan-Sebastian
Published: February 2024

Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013–2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient’s response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs.
ELK1/MTOR/S6K1 Pathway Contributes to Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer
Authors: Zhao Lei , Wang Yifang , Sun Xin , Zhang Xiujuan , Simone Nicole , He Jun
Published: February 2024

The development of acquired resistance to small molecule tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) signaling has hindered their efficacy in treating non-small cell lung cancer (NSCLC) patients. Our previous study showed that constitutive activation of the 70 kDa ribosomal protein S6 kinase 1 (S6K1) contributes to the acquired resistance to EGFR-TKIs in NSCLC cell lines and xenograft tumors in nude mice. However, the regulatory mechanisms underlying S6K1 constitutive activation in TKI-resistant cancer cells have not yet been explored. In this study, we recapitulated this finding by taking advantage of a gefitinib-resistant patient-derived xenograft (PDX) model established through a number of passages in mice treated with increasing doses of gefitinib. The dissociated primary cells from the resistant PDX tumors (PDX-R) displayed higher levels of phosphor-S6K1 expression and were resistant to gefitinib compared to cells from passage-matched parental PDX tumors (PDX-P). Both genetic and pharmacological inhibition of S6K1 increased sensitivity to gefitinib in PDX-R cells. In addition, both total and phosphorylated mechanistic target of rapamycin kinase (MTOR) levels were upregulated in PDX-R and gefitinib-resistant PC9G cells. Knockdown of MTOR by siRNA decreased the expression levels of total and phosphor-S6K1 and increased sensitivity to gefitinib in PDX-R and PC9G cells. Moreover, a transcription factor ELK1, which has multiple predicted binding sites on the MTOR promoter, was also upregulated in PDX-R and PC9G cells, while the knockdown of ELK1 led to decreased expression of MTOR and S6K1. The chromatin immunoprecipitation (ChIP)-PCR assay showed the direct binding between ELK1 and the MTOR promoter, and the luciferase reporter assay further indicated that ELK1 could upregulate MTOR expression through tuning up its transcription. Silencing ELK1 via siRNA transfection improved the efficacy of gefitinib in PDX-R and PC9G cells. These results support the notion that activation of ELK1/MTOR/S6K1 signaling contributes to acquired resistance to gefitinib in NSCLC. The findings in this study shed new light on the mechanism for acquired EGFR-TKI resistance and provide potential novel strategies by targeting the ELK1/MTOR/S6K1 pathway.
Enhancing Essential Oil Extraction from Lavandin Grosso Flowers via Plasma Treatment
Authors: Molina Ricardo , López-Santos Carmen , Balestrasse Karina , Gómez-Ramírez Ana , Sauló Jordi
Published: February 2024

This study explores the impact of plasma treatment on Lavandin Grosso flowers and its influence on the extraction of essential oils (EOs) via hydrodistillation. Short plasma treatment times enhance the yield of EO extraction from 3.19% in untreated samples to 3.44%, corresponding to 1 min of plasma treatment, while longer treatment times (10 min) show diminishing returns to 3.07% of yield extraction. Chemical characterization (GC/MS and ATR-FTIR) indicates that plasma treatments do not significantly alter the chemical composition of the extracted EOs, preserving their aromatic qualities. Investigations into plasma–surface interactions reveal changes at the nanometer level, with XPS confirming alterations in the surface chemistry of Lavandin Grosso flowers by reducing surface carbon and increasing oxygen content, ultimately resulting in an increased presence of hydrophilic groups. The presence of hydrophilic groups enhances the interaction between the surface membrane of the glandular trichomes on Lavandin Grosso flowers and water vapor, consequently increasing the extraction of EOs. Furthermore, microscopic SEM examinations demonstrate that plasma treatments do not affect the morphology of glandular trichomes, emphasizing that surface modifications primarily occur at the nanoscale. This study underscores the potential of plasma technology as a tool to enhance EO yields from botanical sources while maintaining their chemical integrity.
ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells
Authors: Chen Yaoxin , Han Zhenyu , Zhang Sian , Liu Honglin , Wang Ke , Liu Jieyu , Liu Feichang , Yu Shiyun , Sai Na , Mai Haiyan , Zhou Xinying , Zhou Chaoying , Wen Qian , Ma Li
Published: February 2024

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.
MicroRNAs as Plasma Biomarkers of Hepatocellular Carcinoma in Patients with Liver Cirrhosis—A Cross-Sectional Study
Authors: Zenlander Robin , Salter Hugh , Gilg Stefan , Eggertsen Gösta , Stål Per
Published: February 2024

Ultrasound screening for hepatocellular carcinoma (HCC) in patients with liver cirrhosis has a poor sensitivity for small tumors. Circulating microRNAs (miRNAs) have been explored as HCC biomarkers, but results are diverging. Here, we evaluate if miRNAs up-regulated in HCC tissue can be detected in plasma and used as screening biomarkers for HCC. In this cross-sectional study, plasma, HCC tissue and surrounding non-tumorous liver tissue were collected from liver resections. Tissue miRNAs were identified and quantitated by RNA-sequencing analysis, and the fold-changes between HCC and surrounding liver tissue were calculated. The miRNAs up-regulated in HCCs were then re-analyzed in plasma from the same patients, and the miRNAs with the highest plasma levels were subsequently measured in plasma from an independent cohort of patients with cirrhosis or HCC. In tissues from 84 resected patients, RNA-sequencing detected 197 differentially expressed miRNAs, 40 of which had a raw count above 200 and were analyzed in plasma from the same cohort. Thirty-one miRNAs were selected for further analysis in 200 patients with HCC or cirrhosis. Of these, eleven miRNAs were significantly increased in HCC as compared to cirrhosis patients. Only miR-93-5p and miR-151a-3p were significantly associated with HCC, with an AUC of 0.662. In comparison, alpha-fetoprotein and des-gamma-carboxy prothrombin yielded an AUC of 0.816, which increased to 0.832 if miR-93-5p and miR-151a-3p were added. When including sex and age, the addition of miR-93-5p and miR-151a-3p did not further improve the AUC (from 0.910 to 0.911). In conclusion, micro-RNAs up-regulated in HCCs are detectable in plasma but have a poor performance as screening biomarkers of HCC.
Dielectric Barrier Discharge Plasma-Assisted Preparation of Chitosan-Based Hydrogels
Authors: Liang Runing , Zhang Dan , Guo Junwei , Bian Shaohuang , Yang Cheng , A Lusi , Zhang Weiwei , Huang Feng
Published: February 2024

Chitosan is widely used in the production of various hydrogels due to its non-biological toxicity, good biocompatibility, and strong biodegradability. However, chitosan-based hydrogels have not been widely used in tissue engineering due to their poor mechanical strength, poor stability and high biotoxicity of cross-linking agents. As a green technology, low temperature plasma is rich in active groups that can be involved in various chemical reactions, such as replacing the components on the chitosan chain, contributing to the cross-linking of chitosan. In this study, a plasma-assisted preparation method of chitosan-based hydrogels was developed and the properties, including mechanics, water absorption, and degradation (or stability), were characterized and analyzed. It is proved that plasma treatment plays a significant role in improving the mechanical strength and stability of hydrogels.
Multiple Lines of Evidence Support 199 SARS-CoV-2 Positively Selected Amino Acid Sites
Authors: Ferreira Pedro , Soares Ricardo , López-Fernández Hugo , Vazquez Noé , Reboiro-Jato Miguel , Vieira Cristina P. , Vieira Jorge
Published: February 2024

SARS-CoV-2 amino acid variants that contribute to an increased transmissibility or to host immune system escape are likely to increase in frequency due to positive selection and may be identified using different methods, such as codeML, FEL, FUBAR, and MEME. Nevertheless, when using different methods, the results do not always agree. The sampling scheme used in different studies may partially explain the differences that are found, but there is also the possibility that some of the identified positively selected amino acid sites are false positives. This is especially important in the context of very large-scale projects where hundreds of analyses have been performed for the same protein-coding gene. To account for these issues, in this work, we have identified positively selected amino acid sites in SARS-CoV-2 and 15 other coronavirus species, using both codeML and FUBAR, and compared the location of such sites in the different species. Moreover, we also compared our results to those that are available in the COV2Var database and the frequency of the 10 most frequent variants and predicted protein location to identify those sites that are supported by multiple lines of evidence. Amino acid changes observed at these sites should always be of concern. The information reported for SARS-CoV-2 can also be used to identify variants of concern in other coronaviruses.
Correlation of Experimental and Calculated Inhibition Constants of Protease Inhibitor Complexes
Authors: Goettig Peter , Chen Xingchen , Harris Jonathan M.
Published: February 2024

Predicting the potency of inhibitors is key to in silico screening of promising synthetic or natural compounds. Here we describe a predictive workflow that provides calculated inhibitory values, which concord well with empirical data. Calculations of the free interaction energy ΔG with the YASARA plugin FoldX were used to derive inhibition constants Ki from PDB coordinates of protease–inhibitor complexes. At the same time, corresponding KD values were obtained from the PRODIGY server. These results correlated well with the experimental values, particularly for serine proteases. In addition, analyses were performed for inhibitory complexes of cysteine and aspartic proteases, as well as of metalloproteases, whereby the PRODIGY data appeared to be more consistent. Based on our analyses, we calculated theoretical Ki values for trypsin with sunflower trypsin inhibitor (SFTI-1) variants, which yielded the more rigid Pro14 variant, with probably higher potency than the wild-type inhibitor. Moreover, a hirudin variant with an Arg1 and Trp3 is a promising basis for novel thrombin inhibitors with high potency. Further examples from antibody interaction and a cancer-related effector-receptor system demonstrate that our approach is applicable to protein interaction studies beyond the protease field.
TIGAR Deficiency Blunts Angiotensin-II-Induced Cardiac Hypertrophy in Mice
Authors: He Xiaochen , Williams Quinesha A. , Cantrell Aubrey C. , Besanson Jessie , Zeng Heng , Chen Jian-Xiong
Published: February 2024

Hypertension is the key contributor to pathological cardiac hypertrophy. Growing evidence indicates that glucose metabolism plays an essential role in cardiac hypertrophy. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glucose metabolism in pressure overload-induced cardiac remodeling. In the present study, we investigated the role of TIGAR in cardiac remodeling during Angiotensin II (Ang-II)-induced hypertension. Wild-type (WT) and TIGAR knockout (KO) mice were infused with Angiotensin-II (Ang-II, 1 µg/kg/min) via mini-pump for four weeks. The blood pressure was similar between the WT and TIGAR KO mice. The Ang-II infusion resulted in a similar reduction of systolic function in both groups, as evidenced by the comparable decrease in LV ejection fraction and fractional shortening. The Ang-II infusion also increased the isovolumic relaxation time and myocardial performance index to the same extent in WT and TIGAR KO mice, suggesting the development of similar diastolic dysfunction. However, the knockout of TIGAR significantly attenuated hypertension-induced cardiac hypertrophy. This was associated with higher levels of fructose 2,6-bisphosphate, PFK-1, and Glut-4 in the TIGAR KO mice. Our present study suggests that TIGAR is involved in the control of glucose metabolism and glucose transporters by Ang-II and that knockout of TIGAR attenuates the development of maladaptive cardiac hypertrophy.
Selection and Validation of Reference Genes for Gene Expression in Bactericera gobica Loginova under Different Insecticide Stresses
Authors: Wei Hongshuang , Zhang Jingyi , Yang Mengke , Li Yao , Guo Kun , Qiao Haili , Xu Rong , Liu Sai , Xu Changqing
Published: February 2024

Insecticide resistance has long been a problem in crop pest control. Bactericera gobica is a major pest on the well-known medicinal plants Lycium barbarum L. Investigating insecticide resistance mechanisms of B. gobica will help to identify pesticide reduction strategies to control the pest. Gene expression normalization by RT-qPCR requires the selection and validation of appropriate reference genes (RGs). Here, 15 candidate RGs were selected from transcriptome data of B. gobica. Their expression stability was evaluated with five algorithms (Delta Ct, GeNorm, Normfinder, BestKeeper and RefFinder) for sample types differing in response to five insecticide stresses and in four other experimental conditions. Our results indicated that the RGs RPL10 + RPS15 for Imidacloprid and Abamectin; RPL10 + AK for Thiamethoxam; RPL32 + RPL10 for λ-cyhalothrin; RPL10 + RPL8 for Matrine; and EF2 + RPL32 under different insecticide stresses were the most suitable RGs for RT-qPCR normalization. EF1α + RPL8, EF1α + β-actin, β-actin + EF2 and β-actin + RPS15 were the optimal combination of RGs under odor stimulation, temperature, developmental stages and both sexes, respectively. Overall, EF2 and RPL8 were the two most stable RGs in all conditions, while α-TUB and RPL32 were the least stable RGs. The corresponding suitable RGs and one unstable RG were used to normalize a target cytochrome P450 CYP6a1 gene between adult and nymph stages and under imidacloprid stress. The results of CYP6a1 expression were consistent with transcriptome data. This study is the first research on the most stable RG selection in B. gobica nymphs exposed to different insecticides, which will contribute to further research on insecticide resistance mechanisms in B. gobica.