bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Repeated Cisplatin and Monosodium Glutamate on Visceral Sensitivity in Rats
Authors: López-Tofiño Yolanda , López-Gómez Laura , Martín-Ruíz Marta , Uranga Jose Antonio , Nurgali Kulmira , Vera Gema , Abalo Raquel
Published: December 2024

Cisplatin, a chemotherapeutic drug, is known for causing gastrointestinal disorders and neuropathic pain, but its impact on visceral sensitivity is unclear. Monosodium glutamate (MSG) has been shown to improve gastrointestinal dysmotility and neuropathic pain induced by cisplatin in rats. This study aimed to determine if repeated cisplatin treatment alters visceral sensitivity and whether dietary MSG can prevent these changes. Male Wistar HAN rats were treated with saline or cisplatin (2 mg/kg/week, ip) for 5 weeks, and visceral sensitivity to intracolonic mechanical stimulation was recorded after the final cisplatin administration (week 5) and one-week post-treatment (week 6). In a second cohort, rats treated with cisplatin or saline also received MSG (4 g/L) in their drinking water, and visceral sensitivity was evaluated on week 6. Finally, the untouched distal colon was obtained from a third cohort of animals one week after treatment to assess immunocyte infiltration. Cisplatin significantly increased colonic mechanical sensitivity on week 6 but not on week 5. MSG did not prevent cisplatin-induced visceral hypersensitivity on week 6 and even exacerbated it. On week 6, compared with the control, cisplatin (with or without MSG) did not modify the colonic infiltration of eosinophils, macrophages, neutrophils, or mast cells. Although MSG seems to be useful in ameliorating some of the adverse effects of cisplatin, such as gastrointestinal motility disturbances or neuropathic pain, it does not alleviate visceral pain.
Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
Authors: Ossendorff Robert , Kurth Sarah , Wang Su , Jaenisch Max , Assaf Elio , Scheidt Sebastian , Welle Kristian , Burger Christof , Wirtz Dieter C. , Strauss Andreas C. , Schildberg Frank A.
Published: December 2024

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100–0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development.
Epigenetic Inhibitors Differentially Impact TGF-β1 Signaling Cascades in COPD Airway Smooth Muscle Cells
Authors: Reddy Karosham Diren , Xenaki Dikaia , Adcock Ian M. , Oliver Brian G. G. , Zakarya Razia
Published: December 2024

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression. However, a deeper understanding of the complex mechanisms associated with DNA methylation, histone post-translational changes and RNA methylation in the context of regulatory pathways remains to be elucidated. We here report on how DNA methylation and histone acetylation inhibition differentially affect CXCL8 signaling in primary human non-COPD and COPD airway cells. Methods: Airway smooth muscle (ASM) cells, a pivotal cell type in COPD, were isolated from the small airways of heavy smokers with and without COPD. Histone acetylation and DNA methylation were inhibited before the TGF-β1 stimulation of cells. Subsequently, CXCL8 production and the abundance and activation of pertinent transcription regulatory proteins (NF-κB, p38 MAPK and JNK) were analyzed. Results: TGF-β1-stimulated CXCL8 release from ASM cells from ‘healthy’ smoker subjects was significantly modulated by DNA methylation (56.32 pg/mL and 56.60 pg/mL) and acetylation inhibitors (27.50 pg/mL and 48.85 pg/mL) at 24 and 48 h, respectively. However, modulation via the inhibition of DNA methylation (34.06 pg/mL and 43.18 pg/mL) and acetylation (23.14 pg/mL and 27.18 pg/mL) was observed to a lesser extent in COPD ASM cells. These changes were associated with differences in the TGF-β1 activation of NF-κB and MAPK pathways at 10 and 20 min. Conclusions: Our findings offer insight into differential epigenetics in controlling COPD ASM cells and provide a foundation warranting future studies on epigenetic differences associated with COPD diagnosis. This would provide a scope for developing therapeutic interventions targeting signaling and epigenetic pathways to improve patient outcomes.
Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients
Authors: Schiele Phillip , Kolling Stefan , Rosnev Stanislav , Junkuhn Charlotte , Walter Anna Luzie , von Einem Jobst Christian , Stintzing Sebastian , Schöning Wenzel , Sauer Igor Maximilian , Modest Dominik Paul , Heinrich Kathrin , Weiss Lena , Heinemann Volker , Bullinger Lars , Frentsch Marco , Na Il-Kang
Published: December 2024

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions. Samples were collected from healthy donors and metastatic colorectal cancer (mCRC) patients from the FIRE-6-Avelumab phase II study. The machine learning model accurately predicted the FcγRIIIa-V158F polymorphism in 94% of samples. FF homozygous patients showed diminished cetuximab-mediated ADCC compared to VF or VV carriers. In mCRC patients, NK cell dysfunctions were evident as impaired ADCC, decreased CD16 downregulation, and reduced CD137/CD107a induction. Elevated PD1+ NK cell levels, reduced lysis of PDL1-expressing CRC cells and improved NK cell activation in combination with the PDL1-targeting avelumab indicate that the PD1-PDL1 axis contributes to impaired cetuximab-induced NK cell function. Together, these optimized assays effectively identify NK cell dysfunctions in mCRC patients and offer potential for broader application in evaluating NK cell functionality across cancers and therapeutic settings.
How Gender Influences the Motivation and Action Towards Climate Change: A Qualitative Study of Participants from a UK Construction Company
Authors: Ross Fenella , Middleton Campbell , Remes Olivia
Published: December 2024

Climate change will lead to widespread adverse global impacts on nature, people and economies. The importance of gender in tackling climate change is becoming increasingly evident, with the Paris Agreement highlighting this. According to the evidence base, women typically show higher levels of concern and action towards climate change within the general public, within politics and on company boards. However, few studies have investigated the influence of gender on climate concerns and action within the workforce. The construction industry is one of the biggest emitters of greenhouse gases; therefore, this is a key sector to focus on with respect to decarbonisation. Simultaneously, construction is dominated by men and has significant gender inequity issues. Given the importance of including women in climate change decisions, it is important to assess construction employees’ knowledge and awareness regarding this key issue. Quota and snowball sampling techniques were used to recruit UK-based participants (n = 30) from a large engineering/construction company to explore the perceived concern, importance and action towards climate change, and qualitative analysis using NVivo 14 software was employed to identify key themes. This qualitative work provides initial important insights for an industry with one of the largest carbon footprints in the world and that also reports significant gender inequities.
Mechanical Properties of Faecal Sludge and Its Influence on Moisture Retention
Authors: Rayavellore Suryakumar Arun Kumar , Parra-Angarita Sergio Luis , Léonard Angélique , Pocock Jonathan , Septien Santiago
Published: December 2024

The mechanical properties of faecal sludge (FS) influence its moisture retention characteristics to a greater extent than other properties. A comprehensive fundamental characterisation of the mechanical properties is scarcely discussed in the literature. This research focused on bulk and true densities, porosity, particle size distribution and zeta-potential, extracellular polymeric substances, rheology and dilatancy, microstructure analysis, and compactibility in the context of using the FS as a substitute for soil in land reclamation and bioremediation processes. FSs from different on-site sanitation systems were collected from around Durban, South Africa. The porosity of the FSs varied between 42% and 63%, with the zeta-potential being negative, below 10 mV. Over 95% of the particles were <1000 µm. With its presence in the inner part of the solid particles, tightly bound extra-cellular polymeric substances (TB-EPSs) influenced the stability of the sludge by tightly attaching to the cell walls, with the highest being in the septic tank with the greywater sample. More proteins than carbohydrates also confirmed characterised the anaerobic nature of the sludge. The results of the textural properties using a penetrometer showed that the initial slope of the positive part of the penetration curve was related to the stiffness of the sludge sample and similar to that of sewage sludge. The dynamic oscillatory measurements exhibited a firm gel-like behaviour with a linear viscoelastic behaviour of the sludges due to the change in EPSs because of anaerobicity. The high-TS samples exhibited the role of moisture as a lubricating agent on the motion of solid particles, leading to dilatancy with reduced moisture, where the yield stress was no longer associated with the viscous forces but with the frictional contacts of solid–solid particle interactions. The filtration–compression cell test showed good compactibility, but the presence of unbound moisture even at a high pressure of 300 kPa meant that not all unbound moisture was easily removable. The moisture retention behaviour of FS was influenced by its mechanical properties, and any interventional changes to these properties can result in the release of the bound moisture of FS.
Effects of Exergaming on Morphological Variables, Biochemical Parameters, and Blood Pressure in Children and Adolescents with Overweight/Obesity: A Systematic Review with Meta-Analysis of Randomized Controlled Trials
Authors: Hernandez-Martinez Jordan , Perez-Carcamo Joaquín , Melki Hassan , Cid-Calfucura Izham , Vasquez-Carrasco Edgar , Delgado-Floody Pedro , Romero Claudio , Herrera-Valenzuela Tomás , Branco Braulio Henrique Magnani , Valdés-Badilla Pablo
Published: December 2024

Objectives: This systematic review with meta-analysis aimed to evaluate the available body of published peer-reviewed studies on the effects of exergaming (EXG) compared to the control group (CG) on morphological variables, biochemical parameters, and blood pressure in children and adolescents with overweight/obesity. Methods: A systematic literature search was conducted until September 2024 using five databases: PubMed, Medline, CINAHL Complete, Scopus, and Web of Science. PRISMA, TESTEX, RoB 2, and GRADE tools assessed the methodological quality and certainty of evidence. Hedge’s g effect sizes (ES) for morphological, biochemical, and blood pressure variables were calculated for meta-analyses. Using a random effects model, potential sources of heterogeneity were selected, including subgroup analyses (age) and single training factor analysis (program duration, training frequency). The protocol was registered in PROSPERO (code: CRD42024626992). Results: Out of 72 records, 6 randomized controlled trials with 191 children and adolescents with overweight/obesity were included. Nine meta-analyses were performed, showing significant decreases in body mass index (p = 0.04), waist circumference (p = 0.03), and systolic blood pressure (p = 0.007). However, no significant improvements were observed in diastolic blood pressure, body fat percentage, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and glucose. Subgroup analyses showed significant decreases in total cholesterol (<15 years, ES = 0.56; p = 0.006), HDL-cholesterol (<15 years, ES = 0.51; p = 0.01), LDL-cholesterol (<15 years, ES = 0.63; p = 0.01), and triglycerides (<15 years, ES = 0.82; p = 0.000). In training duration, only significant decreases in total cholesterol (ES = 0.69; p = 0.02) were presented in favor of <12 weeks vs. ≥12 weeks. While in training frequency only significant decreases in triglycerides (ES = 0.70; p = 0.03) were reported in favor of ≥3 sessions per week vs. <3 sessions per week. Conclusions: EXG significantly decreases body mass index, waist circumference, and systolic blood pressure in children and adolescents with overweight/obesity.
Neurodevelopmental Disorders and Connective Tissue-Related Symptoms: An Exploratory Case-Control Study in Children
Authors: Zoccante Leonardo , Di Gennaro Gianfranco , Rigotti Erika , Ciceri Marco Luigi , Sbarbati Andrea , Zaffanello Marco
Published: December 2024

Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies.
Feeding Problems Assessment Tools in Children: A Scoping Review
Authors: Destriatania Suci , Februhartanty Judhiastuty , Nurwidya Fariz , Sekartini Rini
Published: December 2024

‘Feeding problems’ is a term used to describe problems that may present typically in children. Problems with feeding during infancy can result in significant negative consequences for a child’s nutrition, growth, and brain development. This scoping review aims to map current research, provide summary of the available feeding problem assessment tools for children, and review current implications and the gaps between tools, providing information that academics, practitioners, and parents may find useful. Three electronic databases (PubMed, Science Direct, and ProQuest) were searched using terms related to feeding problem assessment tools in children, which included, but were not limited to, “feeding difficult*”, “eating problem”, “eating difficult*”, “tool”, “child*”, and “pediatric”. The following limits were implemented on the search: English language, age limit (<18 years old) and publication period (last 10 years). Data management and analysis carried out manually through discussion with the team. Authors 1 and 2 screened titles and abstracts, then full texts were discussed with the full team to identify articles that met inclusion and exclusion criteria. Data were charted into a matrix table based on these categories: author, year, population, assessment tools, usage and aspects. Thematic analysis was carried out to summarize the characteristics of the studies. There were 47 papers included in the study and analysis, in which 23 assessment tools were found. Pedi-EAT was the most frequent assessment tool used in the studies, with nine papers covering this feeding problem assessment tool. MCH–FS came in second for its chosen tool quantifying children’s feeding problems, with a total of seven papers covering this tool, along with BPFAS with seven papers. In this review, 23 assessment tools were validated and tested for reliability. Pedi-EAT, MCH-FS and BPFAS were commonly used instruments. However, it is clear that no single instrument covers comprehensively all aspects of feeding problems in children. In addition, usage of the tools and wide age range indicate that further research is needed to fill the gaps.
Epidemiological and Clinical Characteristics of Pediatric Acute Drug Intoxications: A Retrospective Analysis
Authors: Singer Cristina Elena , Văruț Renata-Maria , Singer Maria , Cosoveanu Simona , Abdul Razzak Jaqueline , Popescu Madalina Elena , Gaman Simina , Petrescu Ileana Octavia , Popescu Cristina
Published: December 2024

Background/Objectives: Acute drug intoxications (ADIs) are a significant concern in pediatric healthcare, contributing to both accidental and intentional morbidity. This study aimed to analyze the demographic, clinical, and therapeutic characteristics of pediatric ADI cases to identify trends and inform preventive strategies. Methods: This retrospective study included 120 cases of pediatric ADI admitted to the Second Pediatric Clinic of Craiova County Emergency Clinical Hospital in 2022 and 2023. The inclusion criteria encompassed children aged 0–17 years with confirmed pharmaceutical intoxications. Cases involving mixed poisonings or non-pharmaceutical substances were excluded. Clinical severity was classified using the Poisoning Severity Score (PSS). Data on demographics, substances involved, clinical presentations, interventions, and outcomes were analyzed. Results: The majority of cases occurred in females (73.3%) and urban residents (77.5%). Accidental intoxications were prevalent in children aged 1–5 years (45%), while intentional ingestions were common in adolescents (47.5%). The most frequently implicated substances included antibiotics (46.7%), benzodiazepines (20.8%), and acetaminophen (15.8%). Severity was classified as mild (44.2%), moderate (26.6%), or severe (29.2%), while treatment primarily included supportive care, intravenous fluids (62.5%), and antidotes (35.8%). Severe cases required respiratory support in 29.2% of the instances. Hospitalization duration significantly decreased from 2022 (3.8 ± 1.9 days) to 2023 (2.3 ± 0.9 days) (p < 0.05), and no fatalities were recorded. Conclusions: Pediatric ADIs predominantly involve accidental ingestions in young children and intentional overdoses in adolescents. Targeted public health strategies, such as parental education, adolescent mental health support, and improved rural healthcare access, are essential to reduce incidence and severity. These findings underscore the need for focused prevention and optimized clinical management.
Wish-Granting Interventions Promote Positive Emotions in Both the Short and Long Term in Children with Critical Illnesses and Their Families
Authors: Roberts Hannah , Cook Jenny , Lee Apple , Loh Wei Kok , Teo Nigel , Yin Yoong Joanne Su , Gorter-Stam Marguerite
Published: December 2024

Background: Wish-granting interventions are recognized as positive experiences for children with critical illness and their families. While the positive effects have been shown in the immediate and short term, data on their long-term effects are lacking. Objectives: To evaluate the effects of wish-granting interventions on children and parents during and post intervention—both in the weeks after, and up to 5 years after—and to examine any differences between these two groups. Methods: A large-scale international survey was distributed to children (aged 13–17 years old in 2023) and their parents across 24 countries who received a wish-granting intervention in the preceding five years by Make-A-Wish Foundation International. Primary outcomes were positive emotions experienced by children and parents during and after the intervention (short term and long term). The secondary outcomes assessed were negative emotions in wish children, and to what extent children and parents felt the intervention created a sense of normalcy, benefitted other family members, created a happy memory, and gave relief from medical treatment, plus the perceived importance of wish-granting interventions. Results: The responses of 535 children and 1062 parents were analyzed. Both groups reported increases in positive emotions during the early intervention stages, peaking when the wish was granted and persisting in the short and long term. No significant differences were found between children and parents during wish-granting or after the intervention. Negative emotions were reported by a minority of children. Over 80% of children and parents felt the intervention created a happy memory and provided relief from their medical treatments. Nearly all children (96.8%) and parents (95.4%) viewed a wish-granting intervention as important for children with a critical illness. Conclusions: Wish-granting interventions can provide positive emotional benefits to both children and their families in both the short and long term.
Editorial for the Special Issue ‘Molecular Breeding and Genetics Research in Plants’
Authors: Tilahun Shimeles
Published: December 2024

Despite significant advancements in plant breeding research, the challenges posed by a growing global population, the impact of abiotic and biotic stresses, and the uncertainties of climate change necessitate continued focus and innovation in plant breeding and genetic studies [...]
Construction of Shoot Apical Meristem cDNA Yeast Library of Brassica napus L. and Screening of Proteins That Interact with the Inflorescence Regulatory Factors BnTFL1s
Authors: Zan Lingxiong , Liu Haidong , Zhao Xutao , Du Dezhi , Li Kaixiang
Published: December 2024

The determinate inflorescence trait of Brassica napus L. is associated with various desirable agricultural characteristics. BnTFL1s (BnaA10.TFL1 and BnaC09.TFL1), which encode the transcription factor TERMINAL FLOWER 1 (TFL1), have previously been identified as candidate genes controlling this trait through map-based cloning. However, the mechanism underlying the effects of the BnTFL1 proteins remains unclear. Further, proteins generally interact with each other to fulfill their biological functions. The objective of this study was to construct a cDNA library of the shoot apical meristem (SAM) of B. napus and screen for proteins that interact with BnTFL1s, to better understand its mechanism of action. The recombination efficiency of the yeast two-hybrid (Y2H) library that we constructed was 100%, with insertion fragment lengths ranging from 750 to 2000 bp and a capacity of approximately 1.44 × 107 CFUs (colony-forming units), sufficient for screening protein interactions. Additionally, the bait vector pGBKT7-BnTFL1s was transformed into yeast cells alongside positive and negative controls, demonstrating no toxicity to the yeast cells and no self-activation. This bait was used to screen the SAM cDNA library of B. napus, ultimately identifying two BnTFL1s-interacting proteins: 14-3-3-like protein GF14 omega GRF2. These interactions were verified through one-to-one interaction experiments. This study provides a foundation for further research on the biological functions of the BnTFL1s genes and their regulatory role in inflorescence formation in B. napus, while providing a reference for studying similar mechanisms in other plants.
The Electric Field Guided HaCaT Cell Migration Through the EGFR/p38 MAPK/Akt Pathway
Authors: Zhou Huajian , Zhang Shihao , Jin Xiaoli , A Chunxian , Gong Peng , Zhao Sanjun
Published: December 2024

Previous studies have shown that the endogenous electric field (EF) is an overriding cure in guiding cell migration toward the wound center to promote wound healing, but the mechanism underlying is unclear. In this study, we investigated the molecular mechanism of electric field-guided cell migration in human keratinocyte HaCaT cells. Our results showed that HaCaT cells migrate toward the anode under EFs. The phosphorylation levels of p38 MAPK and Akt were obviously elevated in the EF. Knocking down p38 MAPK obviously abolished directed migration of HaCaT cells under the EFs. Inhibiting p38 MAPK by SB203580 impaired the EF-guided cell migration. The electric field may guide HaCaT cell migration through the EGFR/p38 MAPK/Akt pathway.
Polydatin-Induced Shift of Redox Balance and Its Anti-Cancer Impact on Human Osteosarcoma Cells
Authors: Cimmino Alessio , Gioia Magda , Clementi Maria Elisabetta , Faraoni Isabella , Marini Stefano , Ciaccio Chiara
Published: December 2024

Cancer cells demonstrate remarkable resilience by adapting to oxidative stress and undergoing metabolic reprogramming, making oxidative stress a critical target for cancer therapy. This study explores, for the first time, the redox-dependent anticancer effects of Polydatin (PD), a glucoside derivative of resveratrol, on the human Osteosarcoma (OS) cells SAOS-2 and U2OS. Using cell-based biochemical assays, we found that cytotoxic doses of PD (100–200 µM) promote ROS production, deplete glutathione (GSH), and elevate levels of both total iron and intracellular malondialdehyde (MDA), which are key markers of ferroptosis. Notably, the ROS scavenger N-acetylcysteine (NAC) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially reverse PD’s cytotoxic effects. Interestingly, PD’s ability to hinder cell adhesion and migration appears independent of its pro-oxidant effect. Analysis of the oxidative stress regulators SIRT1 and Nrf2 at the gene and protein levels using real-time PCR and Western blot indicates an early oxidative response to PD treatment. PD remains effective under tumor-like conditions of hypoxia and serum starvation, and sensitizes OS cells to ROS-inducing chemotherapeutics like doxorubicin (DOX) and cisplatin (CIS). Importantly, PD exhibits minimal toxicity to non-tumorigenic cells (hFOB), suggesting a favorable therapeutic profile. Overall, our findings underscore that PD-induced redox imbalance plays a crucial role in its anti-OS effects, warranting further exploration into the molecular mechanisms behind its pro-oxidant activity.
Advances in RNA-Based Therapeutics: Challenges and Innovations in RNA Delivery Systems
Authors: Liu Yuxuan , Ou Yaohui , Hou Linlin
Published: December 2024

Nucleic acids, as carriers of genetic information, have found wide applications in both medical and research fields, including gene editing, disease diagnostics, and drug development. Among various types of nucleic acids, RNA offers greater versatility compared to DNA due to its single-stranded structure, ability to directly encode proteins, and high modifiability for targeted therapeutic and regulatory applications. Despite its promising potential in biomedicine, RNA-based medicine still faces several challenges. Notably, one of the most significant technical hurdles is achieving efficient and targeted RNA delivery while minimizing immune responses. Various strategies have been developed for RNA delivery, including viral vectors, virus-like particles (VLPs), lipid nanoparticles (LNPs), and extracellular vesicles (EVs). In this review, we explore the applications of these delivery methods, highlight their advantages and limitations, and discuss recent research advancements, providing insights for the future of RNA-based therapeutics.
A Quantitative Approach to Evaluating Multi-Event Resilience in Oil Pipeline Incidents
Authors: Asha Labiba N. , Yodo Nita , Huang Ying
Published: December 2024

This study introduces a quantitative approach to evaluating the resilience of oil pipeline systems against various natural and physical disruptions. Resilience is increasingly essential in critical infrastructure to ensure continuous operations and minimize disruption impacts. However, existing quantitative methods often need specific time-dependent data, making measuring resilience in pipeline infrastructure challenging. To address this gap, this paper proposed a comprehensive framework by integrating the existing incident database with key features of assessing failure probabilities based on historical events and developing multi-event resilience indicators based on system performance under various disruptions. The methodology employs event tree analysis to quantify the probabilities of multiple failure scenarios and their impact on pipeline operations and recovery efforts. The practical application of the proposed approach was demonstrated using real-world oil pipeline incident data from across the United States, covering the period from 2010 to 2022. The focus was on multiple event scenarios involving pipeline disruptions, followed by shutdowns, examining how these events collectively impact pipeline resilience. The results indicate that corrosion failure, equipment failure, and natural hazard damage significantly impact oil pipeline resilience. Corrosion and equipment failures affect resilience primarily due to their frequency, while natural hazard damage, despite its lower occurrence rate, is more unpredictable and often requires more frequent shutdowns. Understanding these failure causes and their impacts is essential for enhancing the resilience and sustainable operation of oil pipeline systems.
Agro-Climatic Zoning of the Territory of Northern Kazakhstan for Zoning of Agricultural Crops Under Conditions of Climate Change
Authors: Baisholanov Saken , Akshalov Kanat , Mukanov Yerbolat , Zhumabek Bakytbek , Karakulov Ergali
Published: December 2024

Assessments of the agro-climatic resources of Northern Kazakhstan are urgently needed in the face of climate change and increasing threats to food security in the world, and they can provide valuable information for specialists in the field of agriculture. To assess the agro-climatic conditions of Northern Kazakhstan, the following agro-climatic indices were used: heat availability, moisture availability, and aridity of the growing season for the period 1991–2023. The research results rendered it possible to build maps of the spatial distribution of agro-climatic indicators, and five agro-climatic zones, ranging from “moderately humid moderately warm” in the north to “very arid moderately hot” in the south of Northern Kazakhstan, were identified. Recommendations were developed with respect to the agro-climatic zoning of main crops, taking into account the climatic resources of Northern Kazakhstan. The data obtained will be used for the strategic planning of the agricultural crop industry in Northern Kazakhstan.
Assessing NOAA/GFDL Models Performance for South American Seasonal Climate: Insights from CMIP6 Historical Runs and Future Projections
Authors: Shimizu Marília Harumi , Anochi Juliana Aparecida , Santos Diego Jatobá
Published: December 2024

Climate prediction is of fundamental importance to various sectors of society and the economy, as it can predict the likelihood of droughts or excessive rainfall in vulnerable regions. Climate models are useful tools in producing reliable climate forecasts, which have become increasingly vital due to the rising impacts of climate change. As global temperatures rise, changes in precipitation patterns are expected, increasing the importance of reliable seasonal forecasts to support planning and adaptation efforts. In this study, we evaluated the performance of NOAA/GFDL models from CMIP6 simulations in representing the climate of South America under three configurations: atmosphere-only, coupled ocean-atmosphere, and Earth system. Our analysis revealed that all three configurations successfully captured key climatic features, such as the South Atlantic Convergence Zone (SACZ), the Bolivian High, and the Intertropical Convergence Zone (ITCZ). However, coupled models exhibited larger errors and lower correlation (below 0.6), particularly over the ocean and the South American Monsoon System, which indicates a poor representation of precipitation compared with atmospheric models. The coupled models also overestimated upward motion linked to the southern Hadley cell during austral summer and underestimated it during winter, whereas the atmosphere-only models more accurately simulated the Walker circulation, showing stronger vertical motion around the Amazon. In contrast, the coupled models simulated stronger upward motion over Northeast Brazil, which is inconsistent with reanalysis data. Moreover, we provided insights into how model biases may evolve under climate change scenarios. Future climate projections for the mid-century period (2030–2060) under the SSP2-4.5 and SSP5-8.5 scenarios indicate significant changes in the global energy balance, with an increase of up to 0.9 W/m2. Additionally, the projections reveal significant warming and drying in most of the continent, particularly during the austral spring, accompanied by increases in sensible heat flux and decreases in latent heat flux. These findings highlight the risk of severe and prolonged droughts in some regions and intensified rainfall in others. By identifying and quantifying the biases inherent in climate models, this study provides insights to enhance seasonal forecasts in South America, ultimately supporting strategic planning, impact assessments, and adaptation strategies in vulnerable regions.
The Impact of the EU’s CBAM on China’s Carbon Emission Policy
Authors: Geng Ruiyu , Cai Qianyi , Wang Hanbin
Published: December 2024

The European Union’s Carbon Border Adjustment Mechanism (CBAM) has not only accelerated the development of China’s energy policy, but it has also posed new obstacles. This paper aims to explore the influence of CBAM at various phases of its evolution on policy formulation for China’s six main high-emission industries. The policy analysis indicates that the Chinese government, in response to the demands of CBAM, has expanded its emission reduction programs. These now include sustainable energy endeavors, like hydrogen, alongside traditional high-emission industries. Moreover, the Chinese government has implemented 39 initiatives for energy conservation and emission reduction. These initiatives seek to restructure industrial frameworks via legislative modifications, enhance manufacturing methodologies, and establish stringent emission regulations. Nonetheless, there is insufficient adherence to policy implementation in China’s high-emission industries, failing to provide substantial reductions in emissions. In light of the demands from the CBAM carbon taxes and its own emission reduction objectives, the Chinese government has prioritized enhancing enforcement in the six main sectors.
Wear and Optical Properties of MoSi2 Nanoparticles Incorporated into Black PEO Coating on TC4 Alloy
Authors: Zhang Hao , Zhu Jiayi , Xia Jingpeng , Sun Shang , Han Jiaping
Published: December 2024

Wear resistance and optical properties are the key point for the application of titanium alloys as structural materials in the aerospace field. To enhance the wear resistance and optical properties of titanium alloys, a black plasma electrolytic oxidation (PEO) coating incorporating MoSi2 nanoparticles was fabricated on the TC4 alloy via the PEO process, with the MoSi2 nanoparticles being in situ doped into the coating. The doping of MoSi2 nano-particles can effectively reduce the pore size of the PEO layer. The nPEO coating exhibited lower surface roughness than that of the PEO layer. The surface hardness of the nPEO coating increased to 42.5 HRC, significantly enhancing the wear resistance of the PEO layer (40.7 HRC). Furthermore, the PEO coatings exhibited better optical property compared to TC alloy, and the incorporation of MoSi2 particles further improved the performance in most wavelength ranges. The infrared emissivity of the nPEO coating was 0.87, a dramatic increase from the 0.38 value of the TC4 alloy. This coating strategy effectively enhances the wear resistance and optical performance of TC4 alloy, which is critical for the surface design of titanium alloys used in aerospace applications.
Atomic Layer Deposition of Y2O3 Thin Films Using Y(MeCp)2(iPr-nPrAMD) Precursor and H2O, and Their Erosion Resistance in CF4-Based Plasma
Authors: Lee Seong , Kim Hyunchang , Kwon Sehun
Published: December 2024

Atomic layer deposition (ALD) of Y2O3 thin films was investigated using Y(MeCp)2(iPr-nPrAMD) precursor and H2O reactant. The self-limiting reaction mechanism of ALD-Y2O3 thin films was confirmed at a growth temperature of 260 °C. And, the saturated growth rate was confirmed to be ~0.11 nm/cycle. Also, it was demonstrated that a wide ALD temperature window from 150 °C to 290 °C maintains a consistent growth rate. ALD-Y2O3 thin films were found to have a typical cubic polycrystalline structure, independent of growth temperature, which can be attributed to their stoichiometric composition of Y2O3, negligible carbon impurity, and high film density, analogous to the Y2O3 bulk. Even at a low growth temperature of 150 °C, ALD-Y2O3 exhibited a markedly lower plasma etching rate (~0.77 nm/min) than that (~4.6 nm/min) of ALD-Al2O3 when using RIE at a plasma power of 400 W with a mixed gas of Ar/CF4/O2. Furthermore, the growth temperature of Y2O3 thin films had minimal impact on the etching rate.
Arabic Temporal Common Sense Understanding
Authors: Alqifari Reem , Al-Khalifa Hend , O’Keefe Simon
Published: December 2024

Natural language understanding (NLU) includes temporal text understanding, which can be complex and encompasses temporal common sense understanding. There are many challenges in comprehending common sense within a text. Currently, there is a limited number of datasets containing temporal common sense in English and there is an absence of such datasets specifically for the Arabic language. In this study, an Arabic dataset was constructed based on an available English dataset. This dataset is considered a valuable resource for the Arabic community. Consequently, different multilingual pre-trained language models (PLMs) were applied to both the English and new Arabic datasets. Based on this, the effectiveness of these models in Arabic and English is compared and discussed. After analyzing the errors, a new categorization of errors was proposed. Finally, the ability of the PLMs to understand the input text and predict temporal features was evaluated. Through this detailed categorization of errors and classification of temporal elements, this study establishes a comprehensive framework aimed at clarifying the specific challenges encountered by PLMs in temporal common sense understanding (TCU). This methodology underscores the urgent need for further research on PLMs’ capabilities for TCU tasks.
A Framework of the Meshless Method for Topology Optimization Using the Smooth-Edged Material Distribution for Optimizing Topology Method
Authors: Huang Jingbo , Long Kai , Chen Yutang , Geng Rongrong , Saeed Ayesha , Zhang Hui , Tao Tao
Published: December 2024

Density variables based on nodal or Gaussian points are naturally incorporated in meshless topology optimization approaches, pursuing distinct topological layouts with solid and void solutions. However, engineering applications have been hampered by the fact that the authentic structure boundary cannot be identified without manual intervention. To alleviate this issue, the Smooth-Edged Material Distribution for Optimizing Topology (SEMDOT) method is developed within the context of meshless approximation. In meshless analysis, the non-overlap cell variables instead of nodal or Gaussian-based variables are adopted to characterize the existence or absence of sub-regions. This work proposes a non-penalized SEMDOT where an interpolation-based heuristic sensitivity expression is utilized. The 2D and 3D compliance minimization problems serve to validate the efficiency and applicability of the proposed non-penalized SEMDOT approach based on the framework of the meshless method. The numerical results demonstrated that the proposed approach is capable of generating final designs with continuous and smooth edges or surfaces.
Main Heat Treatments Currently Applied on Laser Powder Bed-Fused Scalmalloy®: A Review
Authors: Cerri Emanuela , Curti Lorenzo , Ghio Emanuele
Published: December 2024

Scalmalloy® is an Al-Mg-Sc-Zr alloy designed for the additive manufacturing of components used in various industrial applications. It is primarily used in aerospace and automotive fields due to its low density and high strength. The present brief review aims to outline the state-of-the-art heat treatments currently applied on the as-built Scalmalloy®. The as-built alloy shows yield strength values of 256–278 MPa, ultimate tensile strength of 349–350 MPa, and elongation of 19.0–20.0% due to its bimodal microstructure, which is formed by fine and coarse grain zones. These microstructural features lead to an isotropic behaviour of the mechanical properties. Varying the process parameters, yield strength and ultimate tensile strength can reach values higher than 300 MPa and 400 MPa, respectively, maintaining an isotropic behaviour. After direct aging heat treatment (325 °C × 4 h), the yield and ultimate tensile strength values increase up to 456–469 MPa and 512–521 MPa, respectively, while the strain decreases to 12.0–13.0% due to phase precipitation in the α-Al matrix. Notably, the bimodal microstructure remains largely unchanged. The HIP treatment, carried out at 325 °C × 4 h with a pressure of 1000 bar, reduced the porosity (approximatively 0.18%), resulting in further improvements. The yield strength and the ultimate tensile strength rose to 482–493 MPa and 523–547 MPa, respectively.
Effect of Mn Doping on Microstructure and Corrosion Behavior of CoCuNiTi High-Entropy Alloy Coatings
Authors: Ma Mingxing , Wang Zhixin , Zhu Chengjun , Dong Ying , Liu Lixin , Zhao Liang , Cui Qingxue , Zhu Dachuan , Zhang Deliang
Published: December 2024

Mn-doped CoCuNiTi HEACs were prepared on 45 carbon steel substrate by laser cladding. CoCuNiTi and CoCuMnNiTi HEACs are dual-phase structures composed of FCC and BCC. The addition of Mn causes a decrease in the lattice constant and cell volume of the above two phases, as well as an increase in the density of the two phases and the FCC phase content. The microstructures of the two alloys are the typical dendritic structures. Ti and Co elements are enriched in the dendrite region; Cu element is enriched in the interdendrite region; the distribution of Mn is the most uniform in the dendrite and interdendrite regions. The addition of Mn element causes the microstructure to be significantly refined, and the width of the primary dendrite is reduced from 8.10 μm to 4.11 μm. CoCuNiTi alloy belongs to activation dissolution, and the Mn-containing alloy exhibits an obvious passivation zone. The addition of Mn element increases the capacitive reactance arc radius and the maximum phase angle of the alloy, indicating that the corrosion resistance of the Mn-containing alloy is significantly improved.
Preparation and Electrochemical Characterization of Y-Doped Li1.3Al0.3Ti1.7(PO4)3 Solid Electrolytes for Lithium-Metal Batteries
Authors: Yao Zhongran , Qi Fen , Sun Qiang , Ye Lin , Yang Xiaowei , Chao Guojie , Tang Pei , Zhu Kongjun
Published: December 2024

Lithium-conducting NASICON materials have emerged as a promising alternative to organic liquid electrolytes for high-energy-density Li-metal batteries, owing to their superior ionic conductivity and excellent air stability. However, their practical application is hindered by poor sintering characteristics and high grain boundary resistance. In this investigation, Li1.3Al0.3−xYxTi1.7(PO4)3 (LAYTP-x, x = 0.00, 0.01, 0.03, 0.05, and 0.07) were successfully synthesized via conventional solid-state reaction to explore the impact of Y3+ on both ionic conductivity and chemical stability. The structural, morphological, and transport properties of the samples were comprehensively characterized in order to identify the optimal doping concentration. All samples exhibited a NASICON structure with a uniform distribution of Y elements within the electrolyte. Due to its highest relative density (95.8%), the LAYTP-0.03 electrolyte demonstrated the highest total conductivity of 2.03 × 10−4 S cm−1 with a relatively low activation energy of 0.33 eV, making it suitable for solid-state batteries. When paired with the NCM811 cathode, the Li/LAYTP-0.03/NCM811 cell exhibited outstanding electrochemical performance: a high capacity of 155 mAh/g was achieved at 0.2C after 50 cycles with a Coulombic efficiency of approximately 100%, indicating highly reversible lithium plating/stripping facilitated by the LAYTP-0.03 electrolyte. These results suggest that the LAYTP-0.03 ceramic electrolyte could be a promising alternative for developing safe solid-state Li-metal batteries.