bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial–Mesenchymal Transition in Non-Small Cell Lung Cancer Management: Opportunities and Challenges
Authors: Ye Yunyao , Yu Shanxun , Guo Ting , Zhang Sihui , Shen Xiaozhou , Han Gaohua
Published: November 2024

Lung cancer, the leading cause of death worldwide, is associated with the highest morbidity. Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancer cases. Advances in the domain of cancer treatment have improved the prognosis and quality of life of patients with metastatic NSCLC. Nevertheless, tumor progression or metastasis owing to treatment failure caused by primary or secondary drug resistance remains the cause of death in the majority of cases. Epithelial–mesenchymal transition (EMT), a vital biological process wherein epithelial cancer cells lose their inherent adhesion and transform into more invasive mesenchymal-like cells, acts as a powerful engine driving tumor metastasis. EMT can also induce immunosuppression in the tumor environment, thereby promoting cancer development and poor prognosis among patients with NSCLC. This review aims to elucidate the effect of EMT on metastasis and the tumor immune microenvironment. Furthermore, it explores the possible roles of EMT inhibition in improving the treatment efficacy of NSCLC. Targeting EMT may be an ideal mechanism to inhibit tumor growth and progression at multiple steps.
Microsatellite Instability in Urine: Breakthrough Method for Bladder Cancer Identification
Authors: Rico-Méndez Manuel Alejandro , Ayala-Madrigal María de la Luz , González-Mercado Anahí , Gutiérrez-Angulo Melva , Ramírez de Arellano Sánchez Jorge Adrián , Beltrán-Ontiveros Saul Armando , Contreras-Haro Betsabe , Gutiérrez-Hurtado Itzae Adonai , Moreno-Ortiz José Miguel
Published: November 2024

Bladder cancer (BC) is the most common neoplasm of the urinary system and ranks tenth in global cancer incidence. Due to its high recurrence rate and the need for continuous monitoring, it is the cancer with the highest cost per patient. Cystoscopy is the traditional method for its detection and surveillance; however, this is an invasive technique, while non-invasive methods, such as cytology, have a limited sensitivity. For this reason, new non-invasive strategies have emerged, analyzing useful markers for BC detection from urine samples. The identification of tumor markers is essential for early cancer detection and treatment. Urine analysis offers a non-invasive method to identify these markers. Microsatellite instability (MSI) has been proposed as a promising marker for tumor cell detection and guided targeted therapies. Therefore, this review aims to explore the evidence supporting the identification of MSI in exfoliated bladder tumor cells (EBTCs) in the urine, emphasizing its potential as a non-invasive and clinically effective alternative for tumor identification. Furthermore, establishing clinical guidelines is crucial for standardizing its application in oncological screening and validating its clinical utility.
A Comparison of Internal, Marginal, and Incisal Gaps in Zirconia Laminates Fabricated Using Subtractive Manufacturing and 3D Printing Methods
Authors: Noh Mijun , Kim Jaehong
Published: November 2024

DLP printing is a new method for producing zirconia laminates that ensure clinically acceptable gaps in the internal, marginal, and incisal regions. A typical model of a central maxillary incisor was prepped by a dentist and scanned. The laminate was designed using CAD software version 2023. The laminates were fabricated using a milling machine (LSM group) and a DLP printer (LAM group) (N = 20). The gap was evaluated using the silicone replica method at designated measurement points. Statistical analyses were performed. The Shapiro–Wilk and Kolmogorov–Smirnov tests indicated a non-normal distribution, and the Mann–Whitney test was used. The LSM group had wider gaps than the LAM group except at point E (59.5 µm). The LAM group had wider gaps than the LSM group, except at points H (51.70 µm). No significant differences were observed between the LSM and LAM groups at any of the labiolingual measurement points. In the mesiodistal plane, a significant difference was observed between the two groups at point G, which was adjacent to the mesial side (p < 0.05). The results of this study indicate that DLP printing offers an innovative approach for producing zirconia laminates, as the incisal, internal, and marginal gaps are within clinically acceptable ranges compared with the AM method.
The Relation Among Reactive Stepping and Fall-Related Psychological Factors in Multiple Sclerosis
Authors: Takla Taylor N. , Monaghan Patrick G. , Peterson Daniel S. , Fritz Nora E.
Published: November 2024

Purpose: Persons with multiple sclerosis (MS) experience changes in balance, such as poor and reactive stepping, as well as altered fall-related psychological factors, such as increased concern about falling and feared consequences about falling. Such concerns and fear may relate to and influence mobility. However, these relations are poorly understood in people with MS. This study aimed to investigate the relation between reactive stepping performance and fall-related psychological factors, as well as to assess how these relations differ between individuals who have and have not fallen. Methods: In a single session, participants completed measures regarding fall-related psychological factors (balance confidence, concern about falling, and feared consequences of falling) and completed reactive stepping tasks. Following the visit, participants completed weekly surveys for 3 months to report their falls. Spearman rho correlations were computed to examine associations between participants’ reactive stepping performance and their fall-related concerns, confidence, and consequences, with a stratified analysis to compare these associations between fallers and non-fallers. Results: 44 individuals with MS participated in our study, with 27 individuals experiencing 0 falls (non-fallers) and 17 individuals experiencing at least 1 fall (fallers) in the 3-month follow-up period. Better reactive stepping performance was correlated with fewer concerns, greater confidence, and lower feared consequences related to falling. The stratified analysis revealed a greater number of significant associations for non-fallers than fallers, although the small sample of fallers reduced our ability to detect a relationship in this group. Conclusions: Reactive stepping was associated with fall-related psychological factors. Interventions targeting reactive stepping may be beneficial in enhancing fall-related psychological well-being in the MS community.
Effects of Speed-Based Interventions to Reduce Bradykinesia in Individuals with Parkinson’s Disease: A Systematic Review Protocol
Authors: Benfica Poliana , Scianni Aline , Magalhães Jordana , Brito Sherindan , Martins Júlia , Faria Christina
Published: November 2024

Background/Objectives: Bradykinesia is considered one of the most disabling motor symptoms in individuals with Parkinson’s disease (PD). Speed-based interventions are promising for reducing bradykinesia in this population. This systematic review aims to describe speed-based interventions that have been employed for reducing bradykinesia in individuals with PD and verify their effects. Methods: This systematic review protocol was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Electronic searches were performed in MEDLINE, EMBASE, PEDro, LILACS and SciELO databases and gray literature sources. Experimental studies that investigated the effects of speed-based interventions on bradykinesia in individuals with PD will be considered. Two independent reviewers will screen the studies, extract data and assess risk of bias using Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and ROBINS-I (“Risk Of Bias In Non-randomised Studies—of Interventions”). Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assed the quality of evidence. Conclusions: This systematic review will offer information regarding which types of speed-based interventions have been investigated for reducing bradykinesia in individuals with PD. This information may be important for clinical decision making and will help identify gaps in the literature that may be useful for the definition of future research objectives and the planning of new trials. Ethical permission is not required for this study. Systematic review registration: this systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42024543673).
Association of Job Satisfaction, Intention to Stay, Organizational Commitment, and General Self-Efficacy Among Clinical Nurses in Riyadh, Saudi Arabia
Authors: Alshaibani Naif M. , Aboshaiqah Ahmad E. , Alanazi Naif H.
Published: November 2024

Nurse turnover presents a significant challenge for healthcare organizations worldwide, impacting patient care quality and organizational stability. Understanding the determinants of nurse turnover, particularly job satisfaction, intention to stay, organizational commitment, and general self-efficacy, is crucial for developing effective retention strategies. This study aimed to explore the relationships among job satisfaction, intention to stay, organizational commitment, general self-efficacy, and demographic variables. A cross-sectional, correlational research design was employed, with data collected through validated questionnaires distributed to a total convenience sample of 227 clinical nurses in Riyadh, Saudi Arabia between July 2023 and August 2023. Validated measurement tools, including the Job Satisfaction Index, the Intent to Stay Scale, the Organizational Commitment Scale, and the General Self-Efficacy Scale, were utilized. Descriptive statistics were employed to summarize demographic information, and a correlation analysis was conducted to explore the relationships between the study variables. The findings revealed moderate levels of job satisfaction, intention to stay, organizational commitment, and general self-efficacy among the clinical nurses, with significant positive correlations observed among these variables as well as the nurses’ sociodemographic characteristics. Notably, clinical nurses constituted a significant portion of the sample, suggesting the need for targeted interventions tailored to this demographic group as well as non-Saudi nurses (expatriate nurses), particularly in enhancing their organizational commitment and self-efficacy. The study found significant and positive associations between the four study variables and the nurses’ demographic characteristics. Tailored interventions addressing job satisfaction, intent to stay, organizational commitment, self-efficacy, and demographic variables are essential for mitigating nurse turnover. By fostering a supportive work environment and implementing targeted retention strategies informed by demographic insights and determinants of turnover, healthcare organizations can enhance nurse retention rates and ensure a stable and fulfilled nursing workforce.
Behavior Change Techniques in Physical Activity Interventions Targeting Overweight and Obese Children and Adolescents: A Systematic Review
Authors: Peng Sanying , Khairani Ahmad Zamri , Yuan Fang , Uba Abubakar Rabiu , Yang Xiaoming
Published: November 2024

Substantial evidence globally confirms the benefits of physical activity (PA) interventions for the physical and mental health of overweight and obese children and adolescents. However, current research has yet to determine which behavior change techniques (BCTs) are most effective in PA interventions for this population. This systematic review aims to evaluate the application of BCTs in PA interventions for overweight and obese children and adolescents and to identify the most effective BCTs using the promise ratio. Five electronic databases (PubMed, Embase, Cochrane Central, Web of Science, and PsycINFO) were searched up to 31 May 2024, to identify intervention studies meeting the eligibility criteria for promoting PA in the target population. Thirteen studies were included (nine randomized controlled trials and four quasi-experimental studies). The quality of the included studies was assessed using a revised version of the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomized Studies tool. Among the 24 BCTs implemented, the most frequently applied were goal setting (behavior), instruction on how to perform the behavior, feedback on behavior, and self-monitoring of behavior. Action planning, social support, and material incentives showed the most significant potential to promote PA. These findings provide valuable insights for designing future PA interventions for this group, with the potential to improve health outcomes and enhance PA participation among obese children and adolescents.
Static Mechanical Properties of Aeolian Sand Improved with Silt Subjected to Varying Temperature and Pressure
Authors: Cui Bojun , Xu Jian , Shao Xianxian , Xu Dechao , Zhang Bingqi
Published: November 2024

Delineating the mechanical characteristics of aeolian sand improved with silt under temperature action is of great significance for the construction and long-term operation of engineering materials in seasonal frozen areas. Against the backdrop of aeolian sand resource utilization in the western region, local obtainable wind turbine sand and silt were used as raw materials, and a series of triaxial compression tests were conducted on aeolian sand improved with silt through temperature-controlled triaxial testers. The experimental parameters were as follows: silt content of 0%, 5%, 10%, 15%, and 20%; confining pressures of 100 kPa, 200 kPa, and 300 kPa; and temperatures of room temperature, 0 °C, −5 °C, −10 °C, and −15 °C. The results of the experiment demonstrated that the interaction between silt dosage, confining pressure, and temperature effects significantly influenced the triaxial compression strength of aeolian sand improved with silt. As the dosage of silt increased from 0% to 15%, the peak strength of the samples rose by 7.72% to 18.03%. This maximum increase occurred at a silt dosage of 15%. With the increase in confining pressures, the stress–strain relationship curve for the sample exhibits strain softening characteristics. Under varying temperatures, the samples exhibited a consistent pattern of initial shrinkage followed by subsequent expansion. As temperatures decrease, cohesive forces exhibit a wavelike pattern in their variation, with an essentially constant internal friction angle. The research results can provide theoretical support for the selection of building materials in the northwest region, address the issue of regional material shortages, and improve the application of aeolian sand in seasonally frozen areas.
Low-Temperature Cracking and Improvement Methods for Asphalt Pavement in Cold Regions: A Review
Authors: Ma Rui , Li Yiming , Cheng Peifeng , Chen Xiule , Cheng Aoting
Published: November 2024

The advantages of asphalt pavement in terms of driving comfort, construction efficiency, and ease of maintenance have established it as the predominant choice for high-grade pavements at present. However, being highly sensitive to temperature and stress, asphalt performance is significantly influenced by external environmental conditions and loading, making it susceptible to various distress phenomena. Particularly in high-latitude regions, asphalt pavement cracking severely limits asphalt pavement’s functional performance and service lifespan under cold climatic conditions. To enhance the low-temperature cracking resistance of asphalt pavement in cold regions, tools such as VOS viewer 1.6.20 and Connected Papers were utilized to systematically organize, analyze, and summarize relevant research from the past 40 years. The results reveal that temperature shrinkage cracks and thermal fatigue cracks represent the primary forms of asphalt pavement distress in these regions. Cracking in asphalt pavement in cold regions is primarily influenced by structural design, pavement materials, construction technology, and climatic conditions. Among these factors, surface layer stiffness, base layer type, and the rate of temperature decrease exert the most significant impact on cracking resistance, collectively accounting for approximately 45.4% of all cracking-related factors. The low-temperature performance of asphalt pavement can be effectively improved through several strategies, including adopting full-thickness asphalt pavement with a skeleton-dense structure or reduced average particle size, incorporating functional layers, appropriately increasing the thickness of the upper layer and the compaction temperature of the lower layer, utilizing continuous surface layer construction techniques, and applying advanced materials. High-performance modifiers such as SBR and SBS, nanomaterials with good low-temperature performance, and warm mixing processes designed for cold regions have proven particularly effective. Among various improvement methods, asphalt modification has demonstrated superior effectiveness in enhancing the deformation capacity of asphalt and its mixtures, significantly boosting the low-temperature performance of asphalt pavements. Asphalt modification accounts for approximately 50% of the improvement methods evaluated in this study, with an average improvement in low-temperature performance reaching up to 143%. This paper provides valuable insights into the underlying causes of cracking distress in asphalt pavements in cold regions and offers essential guidance for improving the service quality of such pavements in these challenging environments.
Transverse-Direction Post-Seismic Running Safety of Longitudinally Connected Ballastless Track–Continuous Girder Bridge Systems Considering Earthquake Damage State
Authors: Feng Yulin , Xu Shenglin , Wu Bitao , Zhou Wangbao , Liu Xiang , Wu Liangqin , Rao Junhuan , Xiang Ping , Guo Zhongzhao
Published: November 2024

The transverse-direction post-seismic running safety of a longitudinally connected ballastless track-continuous girder bridge (LCBTCGB) system considering earthquake damage state (EDS) was studied. In this study, a simulation model of an LCBTCGB was established, and the post-earthquake damage law of the LCBTCGB was analyzed by selecting the ground motion that had the greatest influence from within the existing studies. The EDS of key interlayer components and the residual deformation law of each layer structure of the LCBTCGB system were defined. Subsequently, the residual deformations and EDS from the simulation model were imported into a coupled dynamic model of the train, track, and bridge. Evaluation of running safety evaluation after an earthquake was carried out with and without considering EDS, and a running safety guidance diagram for after an earthquake is provided. The results revealed that under conditions of rare earthquakes, without considering EDS, the running safety judgment after the earthquake were underestimated, and the risk increased by 13.6%. Following the designed earthquake, the running safety risk after the earthquake increased by 18.7% if EDS was not considered. The risk of the running safety index exceeding the limit did not increase linearly with earthquake intensity with and without considering EDS. When the EDS was considered, derailment coefficients and wheel axle lateral forces exceeded the safety limit value at an earthquake intensity of 0.2 g, whereas these limit values were only exceeded at an earthquake intensity of 0.3 g when EDS is ignored. When the earthquake intensity reached 0.5 g, the influence on the derailment coefficient was greater but the difference in the wheel axle lateral forces was not significant with or without considering EDS. It is suggested that EDS should be considered when post-seismic running safety of LCBTCGBs are analyzed; otherwise, it will lead to misjudgment of running safety after an earthquake.
Eco-Friendly Improvement of Comprehensive Engineering Properties of Collapsible Loess Using Guar Gum Biopolymer
Authors: Zheng Yuesong , Li Tianhao , Qi Daokun , Xi Xiaojuan , Peng Fengzu , Ding Shijun , Nie Zhibao , Hu Xin , Zhao Gaowen , Xiao Bo , Tang Yake , Wang Wenhui
Published: November 2024

Collapsible loess is characterized by its unique soil-forming environment, mineral composition, and microstructure, resulting in poor engineering properties such as high water sensitivity, high collapsibility, high compressibility, and low strength. To improve the poor engineering properties of collapsible loess, we selected a suitable eco-friendly material—guar gum (GG)—for its improvement and reinforcement, and investigated the improvement effect of different GG dosages (0.5~1.5%) and curing ages (0~28 days) on collapsible loess. The mechanical properties of soil samples were determined by direct shear tests, unconfined compressive strength tests, and splitting tests. The water stability of soil samples was evaluated by both cube and sphere crumb tests. SEM and EDS analyses were also conducted to determine the microstructural and mineral changes in soil. The results indicate that the incorporation of GG is beneficial to inhibit the collapsibility of the soil and improves the water stability and strength of the soil. The collapsibility coefficient of loess is reduced to below 0.015 when 0.75% and above of GG is admixed, which is considered a complete loss of its collapsibility. When the GG dosage increases from 0% to 1.25%, the compressive strength and tensile strength of the soil samples increase by 43.5% and 34.9%, respectively. However, by further increasing the GG dosage to 1.5%, the compressive strength and tensile strength decrease by 3.8% and 6% compared to those with 1.25% GG. This indicates that the strength of the specimens shows an increasing trend and then a decreasing trend with the increase in GG dosage, and 1.25% GG was found to be the best modified dosage. Microstructural and mineral analyses indicate that the addition of GG does not change the mineral composition of loess, but, rather, it significantly promotes the agglomeration and bonding of soil particles through cross-linking with Ca2+ ions in the soil to form a biopolymer network, thus achieving a reliable reinforcement effect. Compared with the existing traditional stabilizers, GG is a sustainable and eco-friendly modified material with a higher low-carbon value. Therefore, it is very necessary to mix GG into collapsible loess to eliminate some of the poor engineering properties of loess to meet engineering needs. This study can provide test support for the application and promotion of GG-modified loess in water agriculture and road engineering.
Influence of the Soil Squeezing Effect on the Peripile Soil of Pre-Tensioned H-Type Prestressed Concrete Revetment Pile Construction Based on Field Tests
Authors: Wu Yuedong , Xiao Yu , Liu Jian
Published: November 2024

Pre-tensioned H-type prestressed concrete revetment piles are a newly developed product dedicated to the protection of river, lake, and sea bank embankments, and their cross-section is H-shaped. In this study, a field test of H-type pile soil’s squeezing effect is carried out based on the second phase project of the HujiaShen Line. Pore water pressure, soil displacement, and other parameters of the H-type pile-driving process are monitored in real time. The test results show the following: (1) The influence range of the excess pore water pressure caused by the soil squeezing effect in the horizontal direction is about 14–15D, and in the vertical direction, the pore water pressure within a depth range of about 7D below the pile bottom increases rapidly. Its dissipation rate is fast at first and then slows down, and it completely dissipates 20 days after piling. (2) The excess pore water pressure caused by the soil squeezing effect does not decrease linearly in the radial direction. The soil around the construction pile can be divided into four areas: A, B, C, and D. Among them, A and B belong to the plastic zone, and C and D belong to the elastic zone. (3) The horizontal displacement of the soil occurs within the depth range of 5D from the surface of the pile to the bottom of the pile at the piling location, and the radial influence range is about 8–12D. From a vertical perspective, the main horizontal displacement of the soil occurs in the long section of the pile driven into the soil, showing a “U”-shaped distribution. (4) The dividing point between the vertical displacement uplift and the settlement of the soil appears within the range of 2–3 m from the construction pile, that is, between 5 and 7D. Settlement occurs after the piling is completed, and the settlement rate is fast at first and then slows down. The final settlement of the soil is stable on the 20th day. This research and experiment provide a design reference for the engineering application of pre-tensioned H-type prestressed concrete bank protection piles.
Survival Outcomes for Men over 80 Years Undergoing Transrectal Ultrasound-Guided Prostate Biopsy: A Prospective Analysis
Authors: Alghamdi Dareen , Kernohan Neil , Li Chunhui , Nabi Ghulam
Published: November 2024

Introduction: Prostate cancer is the second most prevalent cancer among elderly males in Western countries. TRUS biopsy remains a standard diagnosing approach for prostate cancer but poses notable risks, particularly in older men, including complications such as sepsis, acute retention, and rectal bleeding, which can lead to substantial morbidity and mortality. This study aimed to evaluate cancer-specific survival outcomes in men aged over 80 years and whether there is any cancer-specific survival advantage for TRUS biopsy procedure. Methods: Between January 2005 and December 2015, we studied outcomes of 200 patients (median age, 82 years) with elevated prostate-specific antigen (PSA) levels (>4.0 ng/mL) and/or abnormal digital rectal examination (DRE) who underwent TRUS biopsy. Each participant was followed up until death using an electronic system and a unique identifier in a defined geographical area. Cancer-specific and overall survival analyses were carried out utilising SPSS, while R Project was employed to construct and evaluate two nomograms survival duration and predict the risk of death post-biopsy. All statistical tests were two-tailed, with significance set at p < 0.05. Results: Amongst the participants, only 24 patients were alive at the end of follow-up (median age, 91 years). The PSA levels ranged from 4.88 to 102.7 ng/mL. Log-rank and Breslow tests indicated that higher PSA levels, the development of metastases, and ISUP grade group 8–10 were associated with shorter survival times. Age, co-morbid conditions, and tumour type were incorporated into the nomogram due to their clinical significance. Patients aged <81 years had lower mortality risk, while those aged >88 years faced higher mortality risks. Complications from the biopsy increased mortality risks in both cancerous and benign cases, and metastasis significantly heightened the likelihood of death. However, co-morbid conditions did not influence survival probability. Conclusions: Our findings underscore that older age (specifically 80 years and above), high Gleason score, metastasis, and elevated PSA levels are predictive of poorer survival outcomes in elderly men following TRUS biopsy.
Navigating the Complexity of Resistance in Lung Cancer Therapy: Mechanisms, Organoid Models, and Strategies for Overcoming Treatment Failure
Authors: Kang Da Hyun , Lee Jisoo , Im Subin , Chung Chaeuk
Published: November 2024

Background: The persistence of chemotherapy-resistant and dormant cancer cells remains a critical challenge in the treatment of lung cancer. Objectives: This review focuses on non-small cell lung cancer and small cell lung cancer, examining the complex mechanisms that drive treatment resistance. Methods: This review analyzed current studies on chemotherapy resistance in NSCLC and SCLC, focusing on tumor microenvironment, genetic mutations, cancer cell heterogeneity, and emerging therapies. Results: Conventional chemotherapy and targeted therapies, such as tyrosine kinase inhibitors, often fail due to factors including the tumor microenvironment, genetic mutations, and cancer cell heterogeneity. Dormant cancer cells, which can remain undetected in a quiescent state for extended periods, pose a significant risk of recurrence upon reactivation. These cells, along with intrinsic resistance mechanisms, greatly complicate treatment efforts. Understanding these pathways is crucial for the development of more effective therapies. Emerging strategies, including combination therapies that target multiple pathways, are under investigation to improve treatment outcomes. Innovative approaches, such as antibody–drug conjugates and targeted protein degradation, offer promising solutions by directly delivering cytotoxic agents to cancer cells or degrading proteins that are essential for cancer survival. The lung cancer organoid model shows substantial promise to advance both research and clinical applications in this field, enhancing the ability to study resistance mechanisms and develop personalized treatments. The integration of current research underscores the need for continuous innovation in treatment modalities. Conclusions: Personalized strategies that combine novel therapies with an in-depth understanding of tumor biology are essential to overcome the challenges posed by treatment-resistant and dormant cancer cells in lung cancer. A multifaceted approach has the potential to significantly improve patient outcomes.
Carbon-Based Catalysts from H3PO4 Activation of Olive Stones for Sustainable Solketal and γ-Valerolactone Production
Authors: Torres-Liñán Javier , García-Rollán Miguel , Ruiz-Rosas Ramiro , Rosas Juana María , Rodríguez-Mirasol José , Cordero Tomás
Published: November 2024

The use of activated carbon-based catalysts for the production of solketal and γ-valerolactone (GVL), two products of interest for biorefinery processes, was investigated. Activated carbons (ACs) were prepared by chemical activation of olive stones, an agricultural byproduct, using H3PO4 to olive stone mass impregnation ratios (IRs) of 1:1 and 3:1, and under nitrogen or air atmosphere. The ACs showed SBET values of 1130–1515 m2/g, owing to the presence of micropores (0.45–0.60 cm3/g). The use of an IR of 3:1 delivered a wider pore size distribution, with mesopore volume increasing up to 1.36 cm3/g. XPS confirmed the presence of phosphorus groups with surface concentrations of 2.2–3.2 wt% strongly bonded the AC surface through C-O-P bonds. The ACs were tested as acid catalysts for the acetalization of glycerol in a stirred batch reactor at temperatures of 30–50 °C, glycerol concentrations of 1.5 to 3.4 mol/L, and 1–3 wt% catalytic loading. The catalytic activity was clearly correlated with the quantity of C-O-P acid groups determined by TPD, which increased when ACs were prepared under air atmosphere. The AC prepared with IR 3:1 under air achieved full selectivity to solketal, with activation energy of 49 kJ/mol and conversion of up to 70%, matching the equilibrium conversion value under the optimum reaction conditions. A bifunctional catalyst was prepared over this AC by deposition of 5 wt% zirconium and tested in stirred batch reactor for the hydrogenation of levulinic acid (LA) using isopropyl alcohol (IPA) as solvent and H2 donor, with LA:IPA ratios from 1:1 to 1:7 and temperatures between 160–200 °C. The catalyst reached full LA conversion and a GVL yield higher than 80% after only 12 h at 200 °C. A test conducted in the presence of water revealed that it was an inhibitor of the reaction. The identification of isopropyl levulinate as an intermediate suggests that the most likely reaction pathway was dehydration, followed by hydrogenation and cyclization, to obtain GVL. Kinetic modelling of the results showed a value of 42 kJ/mol for the hydrogenation step. The reusability of the catalyst was tested for five consecutive reaction cycles, maintaining most of the activity and selectivity towards GVL.
JRM-28, a Novel HDAC2 Inhibitor, Upregulates Plasticity-Associated Proteins in Hippocampal Neurons and Enhances Morphological Plasticity via Activation of CREB: Implications for Alzheimer’s Disease
Authors: Rahman A. F. M. Towheedur , Bulbule Sarojini , Belayet Jawad Bin , Benko Anna , Gottschalk Carl Gunnar , Frick David N. , Arnold Leggy A. , Hossain M. Mahmun , Roy Avik
Published: November 2024

Enhancement of neuronal plasticity by small-molecule therapeutics protects cognitive skills and also ameliorates progressive neurodegenerative pathologies like Alzheimer’s disease (AD) and dementia. One such compound, a novel histone deacetylase 2 (HDAC2) inhibitor named JRM-28, was shown here to enhance dendritic strength, augment spine density, and upregulate post-synaptic neurotransmission in hippocampal neurons. The molecular basis for this effect correlates with JRM-28-induced upregulation of the transcription of cAMP response element-binding protein(CREB), induction of its transcriptional activity, and subsequent stimulation of expressions of CREB-dependent plasticity-associated genes, such as those encoding N-methyl-D-aspartate (NMDA) receptor subunit NR2A and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1. Specifically, JRM-28 stimulated the NMDA- and AMPA-receptor-sensitive ionotropic calcium influx in hippocampal neurons. Interestingly, JRM-28 did not induce NMDA- and AMPA-sensitive calcium influx in hippocampal neurons once the expression of CREB was knocked down by creb siRNA, suggesting the critical role of CREB in JRM-28-mediated upregulation of synaptic plasticity. Finally, JRM-28 upregulated CREB mRNA, CREB-dependent plasticity-associated markers, and ionotropic calcium influx in iPSC-derived AD human neurons, indicating its therapeutic implications in the amelioration of AD pathologies.
Sprouty2 Regulates Endocytosis and Degradation of Fibroblast Growth Factor Receptor 1 in Glioblastoma Cells
Authors: Hausott Barbara , Pircher Lena , Kind Michaela , Park Jong-Whi , Claus Peter , Obexer Petra , Klimaschewski Lars
Published: November 2024

The Sprouty (SPRY) proteins are evolutionary conserved modulators of receptor tyrosine kinase (RTK) signaling. SPRY2 inhibits fibroblast growth factor (FGF) signaling, whereas it enhances epidermal growth factor (EGF) signaling through inhibition of EGF receptor (EGFR) endocytosis, ubiquitination, and degradation. In this study, we analyzed the effects of SPRY2 on endocytosis and degradation of FGF receptor 1 (FGFR1) using two human glioblastoma (GBM) cell lines with different endogenous SPRY2 levels. SPRY2 overexpression (SPRY2-OE) inhibited clathrin- and caveolae-mediated endocytosis of FGFR1, reduced the number of caveolin-1 vesicles and the uptake of transferrin. Furthermore, FGFR1 protein was decreased by SPRY2-OE, whereas EGFR protein was increased. SPRY2-OE enhanced FGFR1 degradation by increased c-casitas b-lineage lymphoma (c-CBL)-mediated ubiquitination, but it diminished binding of phospholipase Cγ1 (PLCγ1) to FGFR1. Consequently, SPRY2-OE inhibited FGF2-induced activation of PLCγ1, whereas it enhanced EGF-induced PLCγ1 activation. Despite the reduction of FGFR1 protein and the inhibition of FGF signaling, SPRY2-OE increased cell viability, and knockdown of SPRY2 enhanced the sensitivity to cisplatin. These results demonstrate that the inhibitory effect of SPRY2-OE on FGF signaling is at least in part due to the reduction in FGFR1 levels and the decreased binding of PLCγ1 to the receptor.
Neurodevelopment of Autism: Critical Periods, Stress and Nutrition
Authors: Ayoub George
Published: November 2024

Autism spectrum disorder (ASD) is a neurodevelopmental disability that presents significant challenges in communication and behavior. ASD prevalence exceeds 2% among eight-year-old children and is at similar levels globally. We propose that critical periods during fetal development and early postnatal years establish the conditions for either neurotypical development or the emergence of autism through mechanisms that influence immune function or delay neuronal development. One critical period is characterized by the requirement for folate, a crucial methyl donor needed for DNA regulation. Insufficient folate availability has been linked to the risk of developing ASD. Another critical period may be affected by oxidative stress or inflammation of the fetal brain, potentially due to inadequate microglial immunity, which can lead to CNS inflammatory changes that disrupt typical neurodevelopment. We suggest that early supplementation with reduced folate and taurine during both the fetal and postnatal stages may be effective in mitigating the severity of ASD symptoms by promoting neurotypical development through these critical neurodevelopmental periods.
Unveiling Smyd-2’s Role in Cytoplasmic Nrf-2 Sequestration and Ferroptosis Induction in Hippocampal Neurons After Cerebral Ischemia/Reperfusion
Authors: Liu Daohang , Zhu Yizhun
Published: November 2024

SET and MYND Domain-Containing 2 (Smyd-2), a specific protein lysine methyltransferase (PKMT), influences both histones and non-histones. Its role in cerebral ischemia/reperfusion (CIR), particularly in ferroptosis—a regulated form of cell death driven by lipid peroxidation—remains poorly understood. This study identifies the expression of Smyd-2 in the brain and investigates its relationship with neuronal programmed cell death (PCD). We specifically investigated how Smyd-2 regulates ferroptosis in CIR through its interaction with the Nuclear Factor Erythroid-2-related Factor-2 (Nrf-2)/Kelch-like ECH-associated protein (Keap-1) pathway. Smyd-2 knockout protects HT-22 cells from Erastin-induced ferroptosis but not TNF-α + Smac-mimetic-induced apoptosis/necroptosis. This neuroprotective effect of Smyd-2 knockout in HT-22 cells after Oxygen–Glucose Deprivation/Reperfusion (OGD/R) was reversed by Erastin. Smyd-2 knockout in HT-22 cells shows neuroprotection primarily via the Nuclear Factor Erythroid-2-related Factor-2 (Nrf-2)/Kelch-like ECH-associated protein (Keap-1) pathway, despite the concurrent upregulation of Smyd-2 and Nrf-2 observed in both the middle cerebral artery occlusion (MCAO) and OGD/R models. Interestingly, vivo experiments demonstrated that Smyd-2 knockout significantly reduced ferroptosis and lipid peroxidation in hippocampal neurons following CIR. Moreover, the Nrf-2 inhibitor ML-385 abolished the neuroprotective effects of Smyd-2 knockout, confirming the pivotal role of Nrf-2 in ferroptosis regulation. Cycloheximide (CHX) fails to reduce Nrf-2 expression in Smyd-2 knockout HT-22 cells. Smyd-2 knockout suppresses Nrf-2 lysine methylation, thereby promoting the Nrf-2/Keap-1 pathway without affecting the PKC-δ/Nrf-2 pathway. Conversely, Smyd-2 overexpression disrupts Nrf-2 nuclear translocation, exacerbating ferroptosis and oxidative stress, highlighting its dual regulatory role. This study underscores Smyd-2’s potential for ischemic stroke treatment by disrupting the Smyd-2/Nrf-2-driven antioxidant capacity, leading to hippocampal neuronal ferroptosis. By clarifying the intricate interplay between ferroptosis and oxidative stress via the Nrf-2/Keap-1 pathway, our findings provide new insights into the molecular mechanisms of CIR and identify Smyd-2 as a promising therapeutic target.
CD38 Inhibitor 78c Attenuates Pro-Inflammatory Cytokine Expression and Osteoclastogenesis in Macrophages
Authors: Lory William , Chowdhury Nityananda , Wellslager Bridgette , Pandruvada Subramanya , Huang Yan , Yilmaz Özlem , Yu Hong
Published: November 2024

CD38, a nicotinamide adenine dinucleotide (NAD+) glycohydrolase, increases during infection or inflammation. Therefore, we aimed to evaluate the effects of a CD38 inhibitor (78c) on NAD+ levels, IL-1β, IL-6, TNF-α cytokine expressions, and osteoclastogenesis. The results show that treatment with 78c on murine BMMs dose-dependently reduced CD38, reversed the decline of NAD+, and inhibited IL-1β, IL-6, and TNF-α pro-inflammatory cytokine levels induced by oral pathogen Porphyromonas gingivalis (Pg) or Aggregatibacter actinomycetemcomitans (Aa) or by advanced glycation end products (AGEs). Additionally, treatment with 78c dose-dependently suppressed osteoclastogenesis and bone resorption induced by RANKL. Treatment with 78c suppressed CD38, nuclear factor kappa-B (NF-κB), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinases (MAPKs) induced by Pg, Aa, or AGEs, and suppressed podosome components (PI3K, Pyk2, Src, F-actin, integrins, paxillin, and talin) induced by RANKL. These results from our studies support the finding that the inhibition of CD38 by 78c is a promising therapeutic strategy to treat inflammatory bone loss diseases. However, treatment with a CD38 shRNA only significantly reduced IL-1β, IL-6, and TNF-α pro-inflammatory cytokine levels induced by AGEs. Compared with controls, it had limited effects on cytokine levels induced by Pg or Aa. Treatment with the CD38 shRNA enhanced RANKL-induced osteoclastogenesis, suggesting that 78c has some off-target effects.
Fast-Response Hydrogen Sensor Based on γ-Al2O3-Modified Graphene
Authors: Shen Bin , Zhang Qinglan , Liu Xinlei , Li Jiazhe , Guan Yu , Xiao Dan
Published: November 2024

The fast response of H2 sensors plays an important role in the early warning of H2 leakage; in this work, a nanoscale γ-Al2O3 carrier material was prepared using the precipitation method and a new hydrogen sensor was prepared by doping and modifying it with graphene. During the detecting part of the experiment, the voltage–current–temperature detecting system was designed based on the principle of voltage division and shunt, and the theoretical operating temperature computational model was established in parallel. After testing, it was shown that the sensor had a good linear relationship for the range of 1000–10,000 ppm H2; the operating temperature was only 176 °C at 1.4 V operating voltage, the T90 response time was 6.69 s, and the average sensitivity and temperature rise characteristics were 28.23 mV/1% H2 and 36.77 °C/1% H2, respectively. Moreover, the calculated theoretical operating temperature and the measured temperature were basically consistent. This work provides a useful reference for further exploration of H2 sensors.
Using Vital Signs for the Early Prediction of Necrotizing Enterocolitis in Preterm Neonates with Machine Learning
Authors: Verhoeven Rosa , Kupers Thijmen , Brunsch Celina L. , Hulscher Jan B. F. , Kooi Elisabeth M. W.
Published: November 2024

Background/Objectives: Necrotizing enterocolitis (NEC), a devastating neonatal gastrointestinal disease mostly seen in preterm infants, lacks accurate prediction despite known risk factors. This hinders the possibility of applying targeted preventive therapies. This study explores the use of vital signs, including cerebral and splanchnic oxygenation, measured with near-infrared spectroscopy in early NEC prediction. Methods: Several machine learning algorithms were trained on data from very preterm patients (<30 weeks gestational age). Time Series FeatuRe Extraction on the basis of scalable hypothesis tests (TSFRESH) extracted significant features from the vital signs of the first 5 postnatal days. We present the F1-scores and area under the precision-recall curve (AUC-PR) of the models. The contribution of separate vital signs to the selected TSFRESH features was also determined. Results: Among 267 patients, 32 developed NEC Bell’s stage > 1. Using a 1:4 NEC:control ratio, support vector machine and logistic regression predicted NEC better than extreme gradient boosting regarding the F1-score (0.82, 0.82, 0.76, resp., p = 0.001) and AUC-PR (0.82, 0.83, 0.77, resp., p < 0.001). Splanchnic and cerebral oxygenation contributed most to the prediction (40.1% and 24.8%, resp.). Conclusions: Using vital signs, we predicted NEC in the first 5 postnatal days with an F1-score up to 0.82. Splanchnic and cerebral oxygenation were the most contributing vital predictors. This pioneering effort in early NEC prediction using vital signs underscores the potential for targeted preventive measures and also emphasizes the need for additional data in future studies.
Identification of Neonatal Factors Predicting Pre-Discharge Mortality in Extremely Preterm or Extremely Low Birth Weight Infants: A Historical Cohort Study
Authors: Dai Zhenyuan , Zhong Xiaobing , Chen Qian , Chen Yuming , Pan Sinian , Ye Huiqing , Tang Xinyi
Published: November 2024

Background/Objectives: This study identified early neonatal factors predicting pre-discharge mortality among extremely preterm infants (EPIs) or extremely low birth weight infants (ELBWIs) in China, where data are scarce. Methods: We conducted a retrospective analysis of 211 (92 deaths) neonates born <28 weeks of gestation or with a birth weight <1000 g, admitted to University Affiliated Hospitals from 2013 to 2024 in Guangzhou, China. Data on 26 neonatal factors before the first 24 h of life and pre-discharge mortality were collected. LASSO–Cox regression was employed to screen predictive factors, followed by stepwise Cox regression to develop the final mortality prediction model. The model’s performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic, calibration curves, and decision curve analysis. Results: The LASSO–Cox model identified 13 predictors that showed strong predictive accuracy (AUC: 0.806/0.864 in the training/validation sets), with sensitivity and specificity rates above 70%. Among them, six predictors remained significant in the final stepwise Cox model and generated similar predictive accuracy (AUC: 0.830; 95% CI: 0.775–0.885). Besides the well-established predictors (e.g., gestational age, 5 min Apgar scores, and multiplicity), this study highlights the predictive value of the maximum FiO2. It emphasizes the significance of the early use of additional doses of surfactant and umbilical vein catheterization (UVC) in reducing mortality. Conclusions: We identified six significant predictors for pre-discharge mortality. The findings highlighted the modifiable factors (FiO2, surfactant, and UVC) as crucial neonatal factors for predicting mortality risk in EPIs or ELBWIs, and offer valuable guidance for early clinical management.
Research Progress of Laser Cladding Coating on Titanium Alloy Surface
Authors: Wang Zhaofeng , Zhang Shuai
Published: November 2024

With the constant progress in industrial technology, titanium alloy has been widely applied in fields such as aerospace, medical equipment, automotive manufacturing and ocean engineering because of its excellent performance due to its light weight and high strength. However, the shortcomings of titanium alloy, such as low hardness, poor wear resistance, and easy oxidation at high temperatures, limit its application range. Laser cladding technology, as an effective means of surface modification, greatly improves the surface properties of titanium alloy by preparing coatings with specific functions on the surface. In this paper, the research progress of laser cladding technology on the titanium alloy surface is reviewed, including the basic principle of laser cladding, process methods, selection of cladding materials, factors affecting the quality of the laser cladding layer and the development and application of functional coatings. Special attention is paid to the research status of wear-resistant coating, corrosion-resistant coating, high-temperature and oxidation-resistant coating and coating for biological applications, and the development trend and future research direction of laser cladding technology are discussed, in order to provide theoretical basis and technical support for the preparation of high-performance titanium alloy coating.