bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptides: Emerging Candidates for the Prevention and Treatment of Skin Senescence: A Review
Authors: Pintea Andrada , Manea Andrei , Pintea Cezara , Vlad Robert-Alexandru , Bîrsan Magdalena , Antonoaea Paula , Rédai Emöke Margit , Ciurba Adriana
Published: January 2025

One class of cosmetic compounds that have raised interest of many experts is peptides. The search for ingredients with good biocompatibility and bioactivity has led to the use of peptides in cosmetic products. Peptides are novel active ingredients that improve collagen synthesis, enhance skin cell proliferation, or decrease inflammation. Based on their mechanism of action, they can be classified into signal peptides, carrier peptides, neurotransmitter inhibitor peptides, and enzyme inhibitor peptides. This review focuses on the main types of peptides and their application in the cosmetic field, underlining their main limitations. One of the most significant drawbacks of cosmetic peptides is their poor permeability through membranes, which limits their delivery and effectiveness. As a result, this review follows the methods used for improving permeability through the stratum corneum. Increasing peptide bioavailability and stability for enhanced delivery to the desired site of action and visible effects have become central points for the latest research due to their promising features. For this purpose, several methods have been identified and described. Physical techniques include thermal ablation (radiofrequency and laser), electrical methods (electroporation, iontophoresis), mechanical approach (microneedles), and ultrasounds. As an alternative, innovative formulations have been developed in nano-systems such as liposomes, niosomes, ethosomes, nanoemulsions, and other nanomaterials to reduce skin irritation and improve product effectiveness. The purpose of this review is to provide the latest information regarding these noteworthy molecules and the reasoning behind their use in cosmetic formulations.
Liver Elastography for Liver Fibrosis Stratification: A Comparison of Three Techniques in a Biopsy-Controlled MASLD Cohort
Authors: Liguori Antonio , Esposto Giorgio , Ainora Maria Elena , Mignini Irene , Borriello Raffaele , Galasso Linda , Paratore Mattia , Giustiniani Maria Cristina , Riccardi Laura , Garcovich Matteo , Gasbarrini Antonio , Miele Luca , Zocco Maria Assunta
Published: January 2025

Background: The aim of this study was to investigate the accuracy in fibrosis staging of a novel shear wave elastography (SWE) device (S-Shearwave Imaging by Samsung) and a previously validated 2D-SWE by Supersonic Imagine (SSI) in patients with biopsy proven metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This prospective study included 75 consecutive patients with MASLD who underwent liver biopsy for suspected MASH. All patients underwent S-Shearwave Imaging by Samsung and 2D-SWE with SSI on the same day of liver biopsy. Fibrosis was histologically assessed using the METAVIR classification system. Agreement between the equipment was assessed with the Pearson coefficient. A receiver operator characteristic curve (ROC) analysis with the Youden index was used to establish thresholds for fibrosis staging. Results: A good correlation was found between S-Shearwave Imaging by Samsung and 2D-SWE with SSI (Pearson’s R = 0.68; p < 0.01). At multivariate regression analysis, S-Shearwave Imaging was associated with advanced fibrosis (≥F3) independently from age, diabetes and platelets (OR 2.94, CI 1.69–5.11, p < 0.01). The fibrosis diagnostic accuracy of both S-Shearwave Imaging and 2D-SWE was good to optimal with AUROCs of 0.81 and 0.70 for significant fibrosis (≥F2), 0.94 and 0.91 for severe fibrosis (≥F3), respectively. The accuracy of S-Shearwave is not significantly different from Fibroscan and Agile3+ (DeLong test p value 0.16 and 0.15, respectively) while is slightly better than 2D-SWE, FIB4 and NFS (DeLong test p value < 0.05). For S-Shearwave Imaging by Samsung, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.9 kPa (Sens 74.4%, Spec 87.5%) and 8.1 kPa (Sens 95.6%, Spec 78.8%). For 2D-SWE by SSI, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.2 kPa (Sens 55.8%, Spec 84.4%) and 7.6 kPa (Sens 82.6%, Spec 84.6%). Conclusion: S-Shearwave Imaging is a useful and reliable non-invasive technique for staging liver fibrosis in patients with MASLD. Its diagnostic accuracy is non-inferior to other shear wave elastography techniques (TE and 2D-SWE by SSI).
Successful Pregnancy Outcome in a Patient Treated with Pembrolizumab and Exposed to Fluoro-Deoxyglucose (18F-FDG) PET/CT: Case Report and Review of Literature
Authors: Mastricci Anna Lucia , Sorrentino Felice , Giansiracusa Elisa , Zanzarelli Erika , De Lucia Graziana Silvana , Fesce Vincenza Fernanda , Nappi Luigi , Vasciaveo Lorenzo
Published: January 2025

Background: Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with 18F-FDG PET/CT, a diagnostic method contraindicated during pregnancy. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are innovative therapies for relapsed HL (rHL) with significant efficacy. However, ICIs can impair immune tolerance, potentially increasing immune-related adverse events. The PD-1/PD-L1 pathway, targeted by pembrolizumab, plays a critical role in maternal–fetal immune adaptation, raising concerns about its safety during pregnancy. Case Report: We report the case of a 36-year-old woman diagnosed with rHL who unknowingly became pregnant during treatment with pembrolizumab and 18F-FDG PET/CT scans. The pregnancy was diagnosed at 24 weeks, after five cycles of pembrolizumab during the first two trimesters and an 18F-FDG PET/CT scan in the first trimester. Following multidisciplinary counseling, the pregnancy was closely monitored, culminating in the delivery of a healthy male infant at 37.5 weeks. Conclusions: This case highlights a favorable maternal–fetal outcome despite exposure to pembrolizumab and 18F-FDG PET/CT during pregnancy. Given the limited data on such exposures, case reports like this are essential for improving counseling and management strategies. Further research and registries are crucial to provide robust evidence for clinical decision-making in these complex scenarios.
Gut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies
Authors: Jaimez-Alvarado Samuel , López-Tenorio Itzel Ivonn , Barragán-De los Santos Javier , Bello-Vega Dannya Coral , Gómez Francisco Javier Roldán , Amedei Amedeo , Berrios-Bárcenas Enrique Alexander , Aguirre-García María Magdalena
Published: January 2025

An intriguing aspect of restrictive cardiomyopathies (RCM) is the microbiome role in the natural history of the disease. These cardiomyopathies are often difficult to diagnose and so result in significant morbidity and mortality. The human microbiome, composed of billions of microorganisms, influences various physiological and pathological processes, including cardiovascular health. Studies have shown that gut dysbiosis, an imbalance in the composition of intestinal bacteria, can contribute to systemic inflammation, a key factor in many cardiovascular conditions. An increase in gut permeability, frequently caused by dysbiosis, allows bacterial endotoxins to enter the bloodstream, activating inflammatory pathways that exacerbate cardiac dysfunction. Recent reports highlight the potential role of microbiome in amyloidogenesis, as certain bacteria produce proteins that accelerate the formation of amyloid fibrils. Concurrently, advancements in amyloidosis treatments have sparked renewed hopes, marking a promising era for managing these kinds of diseases. These findings suggest that the gut–heart axis may be a potential factor in the development and progression of cardiovascular disease like RCM, opening new paths for therapeutic intervention. The aim of this review is to provide a detailed overview of the gut–heart axis, focusing on RCM.
The Neurodevelopmental Dynamics of Multilingual Experience During Childhood: A Longitudinal Behavioral, Structural, and Functional MRI Study
Authors: Della Rosa Pasquale Anthony , Videsott Gerda , Borsa Virginia Maria , Catricalà Eleonora , Pecco Nicolò , Alemanno Federica , Canini Matteo , Falini Andrea , Franceschini Rita , Abutalebi Jubin
Published: January 2025

Background/Objectives: A neurobiological framework of bi- or multilingual neurocognitive development must consider the following: (i) longitudinal behavioral and neural measures; (ii) brain developmental constraints across structure and function; and (iii) the development of global multilingual competence in a homogeneous social environment. In this study, we investigated whether multilingual competence yields early changes in executive attention control mechanisms and their underlying neural structures in the frontal–striatal system, such as the dorsal anterior cingulate cortex/pre-supplemental area and the left caudate. Methods: We employed longitudinal neuroimaging and functional connectivity methods in a small group of multilingual children over two years. Results: We found that the dACC/preSMA is functionally influenced by changes in multilingual competence but not yet structurally adapted, while the left caudate, in a developmental stage, is influenced, adapts, and specializes due to multilingual experience. Furthermore, increases in multilingual competence strengthen connections between the dACC/preSMA, left caudate, and other structures of the cognitive control network, such as the right inferior frontal gyrus and bilateral inferior parietal lobules. Conclusions: These findings suggest that multilingual competence impacts brain “adaptation” and “specialization” during childhood. The results may provide insights and guide future research on experience-expectant and experience-dependent brain plasticity to explain the “interaction” between multilingualism and neurodevelopment.
Unraveling the Association: How Identity Mediates the Impact of Childhood Trauma on Criminal Behavior
Authors: Bogaerts Stefan , Tressová Deni , Feijen Esmée , Janković Marija
Published: January 2025

Previous research has consistently linked childhood trauma to criminal behavior in adulthood, yet the mechanisms driving this association remain poorly understood. This study investigated whether identity mediates this relationship, focusing on three identity constructs: consolidated identity, disturbed identity, and lack of identity. Criminal behavior was operationalized as a dichotomous variable, distinguishing between 103 community participants (53.9%) and 88 forensic psychiatric patients (46.1%) in a sample of 191 male participants (Mage = 39.82, SDage = 14.14). Mediation analysis was conducted using PROCESS macro model 4, controlling for age and overall personality dysfunction. The results demonstrated that childhood trauma was associated with adult criminal behavior. Additionally, childhood trauma was positively associated with lack of identity but showed no significant effect on consolidated and disturbed identity. Likewise, lack of identity was the only identity variable associated with criminal behavior and emerged as the sole mediator between childhood trauma and criminal behavior. These findings underscore the important role of identity, particularly the lack of identity, in understanding pathways to criminal behavior. Interventions aimed at strengthening individuals’ sense of self may help mitigate criminal tendencies in individuals with a history of childhood trauma, though longitudinal research is needed to further validate these findings.
Human–Structure System Coupled Vibration Test and Human Body Model
Authors: Chen Xiaotong , Lin Yaofa , Ye Mao , Wu Liqin
Published: January 2025

Most studies on human–structure interactions have focused on vertical coupling, which refers to the interaction between human bodies and structures in the vertical direction. This study, however, analyzes horizontal coupling. Several experiments on mass–structure and human–structure systems were conducted, and two horizontal-coupling human–structure models are proposed. The experimental results indicate that a stationary human body should not be regarded as a simple mass. As the number of individuals increases, the horizontal self-resonance frequency gradually decreases by approximately 0.2–0.3 Hz, whereas the damping ratio increases. Based on experimental data and horizontal human–structure models, the horizontal frequency ranges of the human body are found to be 0.236–3.748 Hz for front–back motion and 0.194–5.32 Hz for left–right motion. It is proposed that the single-human model and experimental results be extended to crowd–structure interactions.
Vulnerability Assessment of Urban Rail Transit Network—A Case Study of Chongqing
Authors: Xu Lan , Xiang Pengcheng , Qian Yan , Yang Simai , Zhou Tao , Wang Feng
Published: January 2025

Urban rail network vulnerability assessment has become the core of the urban public transport system. Identifying and quantifying the vulnerability of urban rail transit is the key to coping with the crisis situation of the urban rail transit system. The article uses the Space L method based on complex network theory to establish a topological model of the Chongqing rail transit line network, analyze the topological properties of the network, and use MATLAB 2020b software to conduct deliberate attacks on each station to assess the vulnerability of the Chongqing rail transit network in terms of changes in network efficiency. The results show that the density of Chongqing’s rail transit network is low and the network level needs to be improved; there is no significant correlation between the node vulnerability and the degree value of nodes in the network. The identification of important stations can provide a basis for the decision-making of urban rail transit operation managers and has a strong practical value.
Nonlinear Analysis and Optimization of Recycled Aggregate Concrete Cross-Sections Based on Restoring Force Models
Authors: Qi Chaolong , Wang Changqing , Ma Zhiming
Published: January 2025

This research presents a simplified approach using a uniaxial restoring force model to analyze the seismic response of recycled aggregate concrete (RAC) frames. Nonlinear simulations were conducted to explore how factors like axial compression ratio, reinforcement ratio, and cross-sectional geometry affect the ductility and seismic performance of RAC sections. The findings reveal that a reduction in the axial compression ratio from 0.60 to 0.57 results in a 15% increase in ductility, while a higher reinforcement ratio leads to a 20% enhancement. In addition, rectangular sections were found to be more sensitive to variations in material strength than square sections, offering key insights for structural optimization. The method proposed here also enhances computational efficiency by minimizing resource consumption and improving the convergence of nonlinear iterative procedures. These findings provide a theoretical foundation for optimizing the design and seismic evaluation of RAC structures, promoting their broader application in engineering practice.
Prostate Cancer: A Journey Through Its History and Recent Developments
Authors: Mallah Hamza , Diabasana Zania , Soultani Sina , Idoux-Gillet Ysia , Massfelder Thierry
Published: January 2025

Prostate cancer is one of the most common diseases among men worldwide and continues to pose a serious threat to health. This review shows the history and the new developments in the management of prostate cancer, with an emphasis on a range of therapeutic approaches, such as hormone therapy, radiation therapy, surgery, and innovative targeted therapeutics. The evolution of these treatments is examined in light of clinical outcomes, patient quality of life, and emerging resistance mechanisms, such as the recently shown vitamin D-based strategies. New developments that have the potential to increase survival rates and reduce side effects are also discussed, including PARP inhibitors (PARPis), immunotherapy, and tailored medication. Additionally, the use of biomarkers and sophisticated imaging methods in therapeutic decision-making is explored, with a focus on how these tools might improve patient care. The absolute necessity for a multidisciplinary approach for improving treatment strategies is becoming more and more apparent as our understanding of the biology of prostate cancer deepens. This approach ensures that patients receive customized medicines that fit their unique profiles. Future avenues of investigation will focus on resolving issues dealing with treatment efficacy and resistance to improve treatment results, ultimately leading to disease cure for prostate cancer patients.
Liquid Biopsy and Multidisciplinary Treatment for Esophageal Cancer
Authors: Hoshi Yuki , Matsuda Satoru , Takeuchi Masashi , Kawakubo Hirofumi , Kitagawa Yuko
Published: January 2025

Esophageal cancer (EC) is one of the leading causes of cancer-related deaths globally. Surgery is the standard treatment for resectable EC after preoperative chemoradiotherapy or chemotherapy, followed by postoperative adjuvant chemotherapy in certain cases. Upper gastrointestinal endoscopy and computed tomography (CT) are predominantly performed to evaluate the efficacy of these treatments, but their sensitivity and accuracy for evaluating minimal residual disease remain unsatisfactory, thereby requiring the development of alternative methods. In recent years, interest has been increasing in using liquid biopsy to assess treatment responses. Liquid biopsy is a noninvasive technology for detecting cell components in the blood and other body fluids. It involves collecting a small sample of body fluid, which is then analyzed for the presence of components, including circulating tumor DNA (ctDNA), microRNA (miRNA), or circulating tumor cells (CTCs). Further, ctDNA and miRNA are analyzed with various techniques, including digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS). CTCs are isolated by determining surface antigens using immunomagnetic techniques or by filtering the blood according to cell size and rigidity. Several studies indicate that investigating these materials helps predict EC prognosis and recurrence and possibly stratifies high-risk groups. Liquid biopsy may also apply to the selection of cases that have achieved a complete response through preoperative treatment to prevent surgery and preserve the esophagus, as well as identifying the suitability of postoperative chemotherapy and the timing of conversion surgery for unresectable EC. The potential of liquid biopsy to enhance treatment decisions will further advance EC treatment.
How Can We Improve the Survival of Patients with Colorectal Liver Metastases Using Thermal Ablation?
Authors: Masuda Toshiro , Beppu Toru , Okabe Hirohisa , Imai Katsunori , Hayashi Hiromitsu
Published: January 2025

Thermal ablation has been widely used for patients with small colorectal liver metastases (CRLMs), even for resectable cases; however, solid evidence has been scarce. (1) Thermal ablation versus liver resection. Some propensity-score matching studies using patients with balanced baseline characteristics have confirmed less invasiveness and the comparable survival benefits of thermal ablation to liver resection. A more recent pivotal randomized controlled trial comparing thermal ablation and liver resection was presented during the American Society of Clinical Oncology 2024 meeting. Diameter ≤ 3 cm, ten or fewer resectable and ablatable CRLMs were assigned to thermal ablation or liver resection. No differences were observed in the overall survival and local and distant progression-free survival with less morbidity. (2) Combination of thermal ablation and liver resection. Four matching studies demonstrated comparable data between the combination and liver resection alone groups in the long-term survival and recurrence rates without increasing the postoperative complication rates. The selection of the two approaches depends primarily on the number, size, and location of the CRLMs. (3) Chemotherapy in combination with thermal ablation. A propensity-score matching study comparing thermal ablation ± neoadjuvant chemotherapy was conducted. The addition of neoadjuvant chemotherapy was an independent predictive factor for good progression-free survival without increasing morbidity. Two randomized controlled trials demonstrated that additional thermal ablation to systemic chemotherapy can improve the overall survival for initially unresectable CRLMs. (4) Conclusions. Thermal ablation can provide survival benefits for patients with CRLMs in various situations, keeping adequate indications.
Theoretical Study on the Effect of Pd/Zn Ratio on Benzene Hydrogenation Catalytic Activity and Selectivity
Authors: Cui Yuke , Wang Ning , Han Jingli , Wang Zhiyuan , Zhang Meng , Peng Zhikun , Liu Zhongyi , Illas Francesc , Yang Yongpeng
Published: January 2025

Partial hydrogenation of benzene is the main approach to cyclohexene synthesis in industry. Here, the reaction mechanisms of benzene hydrogenation on Pd-Zn bimetallic catalysts were studied using density functional theory, with the aim of understanding the effect of different Pd/Zn ratios on catalytic activity and cyclohexene selectivity. Three different surfaces, Pd(111), Pd4Zn1(111), and Pd2Zn1(111), were considered as catalyst models. It was found that increasing the Zn concentration decreases the hydrogenation energy barriers while also hindering the reverse reactions. These findings are corroborated by microkinetic simulations and also indicate that cyclohexene selectivity increases with higher Zn concentration but at the expense of reaction activity, which decreases due to the weaker C6H6* and H* adsorption strength in systems with high Zn concentration. The hydrogen coverage has a significant effect on the reaction activity, degree of rate control coefficient, and apparent activation energy as well. For the high hydrogen coverage situations, C6H9 hydrogenation is the rate-controlling step on H1.0/Pd(111) at all considered temperatures, but the degree of rate control for the C6H11 hydrogenation step significantly increases at high temperatures. For H0.8/Pd4Zn1(111), the rate-controlling step changes from C6H7 hydrogenation to C6H9 hydrogenation with increasing temperature, and for H0.67/Pd2Zn1(111), it changes from C6H7 and C6H8 hydrogenation to C6H10 hydrogenation.
Chronic Rapamycin Prevents Electrophysiological and Morphological Alterations Produced by Conditional Pten Deletion in Mouse Cortex
Authors: Hauptman Jason S. , Antonios Joseph , Mathern Gary W. , Levine Michael S. , Cepeda Carlos
Published: January 2025

Abnormalities in the mammalian target of the rapamycin (mTOR) pathway have been implicated in numerous developmental brain disorders. While the molecular and histological abnormalities have been described, less is known about alterations in membrane and synaptic excitability with chronic changes in the mTOR pathway. In the present study, we used a conditional mouse model with a deletion of the phosphatase and tensin homologue (Pten-/-, a negative regulator of mTOR) from cortical pyramidal neurons (CPNs). Whole-cell patch clamp recordings in ex vivo slices examined the intrinsic and synaptic membrane properties of layer II/III CPNs in normal mice treated with rapamycin for four weeks, and Pten-/- mice with and without chronic treatment with rapamycin. Compared with control mice, CPNs from Pten-/- mice demonstrated increased membrane capacitance and time constant in association with increased neuronal somatic size, reduced neuronal firing, and decreased frequency of spontaneous and miniature inhibitory postsynaptic currents, consistent with decreased pre-synaptic GABA release. Rapamycin treatment for four weeks prevented these changes in Pten-/- mice. CPNs from normal mice chronically treated with rapamycin, compared with CPNs from naïve mice, showed reduced capacitance and time constant, increased input resistance, and changes in inhibitory synaptic inputs, consistent with increased pre-synaptic GABA release. These results support the concept that Pten deletion results in significant changes in inhibitory inputs onto CPNs, and these alterations can be prevented with chronic rapamycin treatment. In addition, normal mice treated with rapamycin also display altered membrane and synaptic properties. These findings have potential implications for the treatment of neurological disorders associated with mTOR pathway dysfunction, such as epilepsy and autism.
Twist-Induced Epithelial-to-Mesenchymal Transition Confers Specific Metabolic and Mitochondrial Alterations
Authors: Parker Haleigh N. , Haberman Kayla L. , Ojo Tolulope , Watkins Juli , Nambiar Adhwaitha , Morales Kayla , Zechmann Bernd , Taube Joseph H.
Published: January 2025

Cells undergo significant epigenetic and phenotypic change during the epithelial-to-mesenchymal transition (EMT), a process observed in development, wound healing, and cancer metastasis. EMT confers several advantageous characteristics, including enhanced migration and invasion, resistance to cell death, and altered metabolism. In disease, these adaptations could be leveraged as therapeutic targets. Here, we analyze Twist-induced EMT in non-transformed HMLE cells as well as a breast cancer cell line with (MDA-MB-231) and without (MCF7) EMT features to compare differences in metabolic pathways and mitochondrial morphology. Analysis of oxidative and glycolytic metabolism reveals a general EMT-associated glycolytic metabolic phenotype accompanied by increased ATP production. Furthermore, a decrease in mitochondrial size was also associated with EMT-positive cells. However, mitochondrial elongation and spatial dynamics were not consistently altered, as HMLE Twist cells exhibit more rounded and dispersed mitochondria compared to control, while MDA-MB-231 cells exhibit more elongated and clustered mitochondria compared to MCF7 cells. These results provide further insight as to the contextual nature of EMT conferred properties.
The Effects of Circadian Rhythm on Lead-Induced Toxicity in the DBC1.2 Olfactory Dark Basal Cell Line
Authors: Kamogashira Teru , Kikuta Shu , Yamasoba Tatsuya
Published: January 2025

Background/Objectives: This study evaluated changes in circadian clock genes and mitochondrial function in a lead (Pb)-induced toxicity model of an olfactory epithelial cell line. Methods: The DBC1.2 olfactory dark basal cell line was used. Dexamethasone shock was used to reset the circadian clock 24 h (Group 1) and 36 h (Group 2) after seeding. Then, 60 h after seeding, the cells were treated with or without Pb (II) nitrate in HEPES buffer for 1 h. Mitochondrial function and cell viability were evaluated 84 h after seeding. Results: Mitochondrial function under Pb exposure was significantly impaired in Group 1 compared with Group 2. Cell numbers and viability did not significantly differ between groups. The mitochondrial membrane potential was significantly higher in Group 1 than Group 2, both without and with Pb exposure. Conclusions: The circadian rhythm can alter the sensitivity to Pb-induced toxicity and mitochondrial damage in olfactory cells.
Extracellular Vesicles Derived from Human Umbilical Mesenchymal Stem Cells Transfected with miR-7704 Improved Damaged Cartilage and Reduced Matrix Metallopeptidase 13
Authors: Wu Kun-Chi , Yang Hui-I , Chang Yu-Hsun , Chiang Raymond Yuh-Shyan , Ding Dah-Ching
Published: January 2025

We aimed to explore the therapeutic efficacy of miR-7704-modified extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) for osteoarthritis (OA) treatment. In vitro experiments demonstrated the successful transfection of miR-7704 into HUCMSCs and the isolation of EVs from these cells. In vivo experiments used an OA mouse model to assess the effects of the injection of miR-7704-modified EVs intra-articularly. Walking capacity (rotarod test), cartilage morphology, histological scores, and the expression of type II collagen, aggrecan, interleukin-1 beta, and matrix metalloproteinase 13 (MMP13) in the cartilage were evaluated. The EVs were characterized to confirm their suitability for therapeutic use. IL-1beta-treated chondrocytes increased type II collagen and decreased MMP13 after treatment with miR-7704-overexpressed EVs. In vivo experiments revealed that an intra-articular injection of miR-7704-overexpressed EVs significantly improved walking capacity, preserved cartilage morphology, and resulted in higher histological scores compared to in the controls. Furthermore, the decreased expression of MMP13 in the cartilage post treatment suggests a potential mechanism for the observed therapeutic effects. Therefore, miR-7704-overexpressed EVs derived from HUCMSCs showed potential as an innovative therapeutic strategy for treating OA. Further investigations should focus on optimizing dosage, understanding mechanisms, ensuring safety and efficacy, developing advanced delivery systems, and conducting early-phase clinical trials to establish the therapeutic potential of HUCMSC-derived EVs for OA management.
Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders
Authors: Park Min Kyu , Yang Hyun Wook , Woo Seo Young , Kim Dong Yeon , Son Dae-Soon , Choi Bo Young , Suh Sang Won
Published: January 2025

Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function. Elevated PDE4 activity impairs synaptic plasticity by reducing cAMP levels and protein kinase A (PKA) activity, contributing to cognitive decline, acute brain injuries, and neuropsychiatric conditions such as bipolar disorder and schizophrenia. Similarly, PDE5 dysregulation disrupts nitric oxide (NO) signaling and protein kinase G (PKG) pathways, which are involved in cerebrovascular homeostasis, recovery after ischemic events, and neurodegenerative processes in Alzheimer’s, Parkinson’s, and Huntington’s diseases. PDE4 and PDE5 are promising therapeutic targets for neurological disorders. Pharmacological modulation of these enzymes offers potential to enhance cognitive function and mitigate pathological mechanisms underlying brain injuries, neurodegenerative diseases, and psychiatric disorders. Further research into the regulation of PDE4 and PDE5 will advance therapeutic strategies for these conditions.
Sensing and Degradation of Organophosphorus Compounds by Exploitation of Heat-Loving Enzymes
Authors: Manco Giuseppe , Lampitella Eros A. , Achanta Nagendra S. K. , Catara Giuliana , Marone Maria , Porzio Elena
Published: January 2025

The increasing incidence of organophosphate (OP) pesticide poisoning and the use of OP chemical warfare agents (CWA) in conflicts and terrorist acts need sustainable methods for sensing, decontamination, and detoxification of OP compounds. Enzymes can serve as specific, cost-effective biosensors for OPs. We will report on recent advancements in the use of carboxylesterases from the Hormone-Sensitive Lipase for the detection of OP compounds. In addition, enzymatic-based OP detoxification and decontamination offer long-term, environmentally friendly benefits compared to conventional methods such as chemical treatment, incineration, neutralization, and volatilization. Enzymatic detoxification has gained attention as an alternative to traditional OP-detoxification methods. This review provides an overview of the latest research on enzymatic sensing and detoxification of OPs, by exploiting enzymes, isolated from thermophilic/extremophilic Bacteria and Archaea that show exceptional thermal stability and stability in other harsh conditions. Finally, we will make examples of integration between sensing and decontamination systems, including protein engineering to enhance OP-degrading activities and detailed characterization of the best variants.
GFAPβ and GFAPδ Isoforms Expression in Mesenchymal Stem Cells, MSCs Differentiated Towards Schwann-like, and Olfactory Ensheathing Cells
Authors: Carrillo González Nidia Jannette , Reyes Gutierrez Gabriela Stefania , Campos-Ordoñez Tania , Castro-Torres Rubén D. , Beas Zárate Carlos , Gudiño-Cabrera Graciela
Published: January 2025

Olfactory ensheathing cells (OECs) and mesenchymal stem cells (MSCs) differentiated towards Schwann-like have plasticity properties. These cells express the Glial fibrillary acidic protein (GFAP), a type of cytoskeletal protein that significantly regulates many cellular functions, including those that promote cellular plasticity needed for regeneration. However, the expression of GFAP isoforms (α, β, and δ) in these cells has not been characterized. We evaluated GFAP isoforms (α, β, and δ) expression by Polymerase Chain Reaction (PCR) assay in three conditions: (1) OECs, (2) cells exposed to OECs-conditioned medium and differentiated to Schwann-like cells (dBM-MSCs), and (3) MSC cell culture from rat bone marrow undifferentiated (uBM-MSCs). First, the characterization phenotyping was verified by morphology and immunocytochemistry, using p75, CD90, and GFAP antibodies. Then, we found the expression of GFAP isoforms (α, β, and δ) in the three conditions; the expression of the GFAPα (10.95%AUC) and GFAPβ (9.17%AUC) isoforms was predominantly in OECs, followed by dBM-MSCs (α: 3.99%AUC, β: 5.66%AUC) and uBM-MSCs (α: 2.47%AUC, β: 2.97%AUC). GFAPδ isoform has a similar expression in the three groups (OEC: 9.21%AUC, dBM-MSCs: 11.10%AUC, uBM-MSCs: 9.21%AUC). These findings suggest that expression of different GFAPδ and GFAPβ isoforms may regulate cellular plasticity properties, potentially contributing to tissue remodeling processes by OECs, dBM-MSCs, and uBM-MSCs.
Topological Cavity Chains via Shifted Photonic Crystal Interfaces
Authors: Li Wei , Hu Junhui , Wang Hai-Xiao
Published: January 2025

Recent advances in topological photonics provide unprecedented opportunities to realize a photonic cavity. A recent work shows that the electromagnetic wave can be effectively trapped via the shifted photonic crystal interfaces (SPCIs), which offers an alternative approach to realizing the photonic cavity. Here, we proposed one-dimensional topological insulators based on an SPCIs-induced cavity chain, which is analogous to the Su–Schrieffer–Hegger model and is compatible with the silicon-on-insulator platform. Owing to the asymmetry feature of SPCIs-induced cavities, the topological cavity chains can be either realized by alternating the cavity modes or by tuning the distance between two cavities. The nontrivial band topology of SPCIs-induced cavity chains is further confirmed by observing topological end states, which exhibit robustness against geometrical imperfections. Our work holds promises for designing robust photonic devices, which may find potential applications in future integrated photonics.
Mathematical Modeling of Properties and Structures of Crystals: From Quantum Approach to Machine Learning
Authors: Matyszczak Grzegorz , Jasiak Christopher , Rusinkiewicz Gabriela , Domian Kinga , Brzozowski Michał , Krawczyk Krzysztof
Published: January 2025

The crystalline state of matter serves as a reference point in the context of studies of properties of a variety of chemical compounds. This is due to the fact that prepared crystalline solids of practically useful materials (inorganic or organic) may be utilized for the thorough characterization of important properties such as (among others) energy bandgap, light absorption, thermal and electric conductivity, and magnetic properties. For that reason it is important to develop mathematical descriptions (models) of properties and structures of crystals. They may be used for the interpretation of experimental data and, as well, for predictions of properties of novel, unknown compounds (i.e., the design of novel compounds for practical applications such as photovoltaics, catalysis, electronic devices, etc.). The aim of this article is to review the most important mathematical models of crystal structures and properties that vary, among others, from quantum models (e.g., density functional theory, DFT), through models of discrete mathematics (e.g., cellular automata, CA), to machine learning (e.g., artificial neural networks, ANNs).
Detection of Intracranial Hemorrhage from Computed Tomography Images: Diagnostic Role and Efficacy of ChatGPT-4o
Authors: Koyun Mustafa , Cevval Zeycan Kubra , Reis Bahadir , Ece Bunyamin
Published: January 2025

Background/Objectives: The role of artificial intelligence (AI) in radiological image analysis is rapidly evolving. This study evaluates the diagnostic performance of Chat Generative Pre-trained Transformer Omni (GPT-4 Omni) in detecting intracranial hemorrhages (ICHs) in non-contrast computed tomography (NCCT) images, along with its ability to classify hemorrhage type, stage, anatomical location, and associated findings. Methods: A retrospective study was conducted using 240 cases, comprising 120 ICH cases and 120 controls with normal findings. Five consecutive NCCT slices per case were selected by radiologists and analyzed by ChatGPT-4o using a standardized prompt with nine questions. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated by comparing the model’s results with radiologists’ assessments (the gold standard). After a two-week interval, the same dataset was re-evaluated to assess intra-observer reliability and consistency. Results: ChatGPT-4o achieved 100% accuracy in identifying imaging modality type. For ICH detection, the model demonstrated a diagnostic accuracy of 68.3%, sensitivity of 79.2%, specificity of 57.5%, PPV of 65.1%, and NPV of 73.4%. It correctly classified 34.0% of hemorrhage types and 7.3% of localizations. All ICH-positive cases were identified as acute phase (100%). In the second evaluation, diagnostic accuracy improved to 73.3%, with a sensitivity of 86.7% and a specificity of 60%. The Cohen’s Kappa coefficient for intra-observer agreement in ICH detection indicated moderate agreement (κ = 0.469). Conclusions: ChatGPT-4o shows promise in identifying imaging modalities and ICH presence but demonstrates limitations in localization and hemorrhage type classification. These findings highlight its potential for improvement through targeted training for medical applications.
Subdiffusion Equation with Fractional Caputo Time Derivative with Respect to Another Function in Modeling Superdiffusion
Authors: Kosztołowicz Tadeusz
Published: January 2025

Superdiffusion is usually defined as a random walk process of a molecule, in which the time evolution of the mean-squared displacement, σ2, of the molecule is a power function of time, σ2(t)∼t2/γ, with γ∈(1,2). An equation with a Riesz-type fractional derivative of the order γ with respect to a spatial variable (a fractional superdiffusion equation) is often used to describe superdiffusion. However, this equation leads to the formula σ2(t)=κt2/γ with κ=∞, which, in practice, makes it impossible to define the parameter γ. Moreover, due to the nonlocal nature of this derivative, it is generally not possible to impose boundary conditions at a thin partially permeable membrane. We show a model of superdiffusion based on an equation in which there is a fractional Caputo time derivative with respect to another function, g; the spatial derivative is of the second order. By choosing the function in an appropriate way, we obtain the g-superdiffusion equation, in which Green’s function (GF) in the long time limit approaches GF for the fractional superdiffusion equation. GF for the g-superdiffusion equation generates σ2 with finite κ. In addition, the boundary conditions at a thin membrane can be given in a similar way as for normal diffusion or subdiffusion. As an example, the filtration process generated by a partially permeable membrane in a superdiffusive medium is considered.
Entropy-Based Stochastic Optimization of Multi-Energy Systems in Gas-to-Methanol Processes Subject to Modeling Uncertainties
Authors: Wang Xueteng , Wang Jiandong , Wei Mengyao , Yue Yang
Published: January 2025

In gas-to-methanol processes, optimizing multi-energy systems is a critical challenge toward efficient energy allocation. This paper proposes an entropy-based stochastic optimization method for a multi-energy system in a gas-to-methanol process, aiming to achieve optimal allocation of gas, steam, and electricity to ensure executability under modeling uncertainties. First, mechanistic models are developed for major chemical equipments, including the desulfurization, steam boilers, air separation, and syngas compressors. Structural errors in these models under varying operating conditions result in noticeable model uncertainties. Second, Bayesian estimation theory and the Markov Chain Monte Carlo approach are employed to analyze the differences between historical data and model predictions under varying operating conditions, thereby quantifying modeling uncertainties. Finally, subject to constraints in the model uncertainties, equipment capacities, and energy balance, a multi-objective stochastic optimization model is formulated to minimize gas loss, steam loss, and operating costs. The entropy weight approach is then applied to filter the Pareto front solution set, selecting a final optimal solution with minimal subjectivity and preferences. Case studies using Aspen Hysys-based simulations show that optimization solutions considering model uncertainties outperform the counterparts from a standard deterministic optimization in terms of executability.
Advancing Middle Level Leadership: Middle School Principal Preparation Programs and Approaches to Leadership
Authors: Williams Toni M. , Burgess W. Keith
Published: January 2025

Middle school principals are essential to creating a successful learning environment. They should possess expertise in adolescent development, foster a diverse and equitable school community, and invest in teacher development. This review searched, organized, and analyzed the literature between 2019 and 2024 specifically regarding middle school principal preparation programs and leadership approaches. We sought to identify any alignment with the leadership and organization characteristics outlined in the Association of Middle Level Education’s The Successful Middle School: This We Believe framework The findings revealed a slight relationship between principal preparation programs and the leadership and organizational characteristics outlined by Bishop and Harrison. Our findings also revealed that many states lack specific credentialing requirements for middle school principals. To strengthen the field of middle school education, specifically principal preparation, further research will help educational leaders align their practices with middle school characteristics and advocate for the required credentials in this field.
Dual-Layer Real-Time Scheduling Strategy for Electric Vehicle Charging and Discharging in a Microgrid Park Based on the “Dual Electricity Price Reservation—Surplus Refund Without Additional Charges Mechanism”
Authors: Sun Lixiang , Xie Chao , Zhang Gaohang , Ding Ying , Gao Yun , Liu Jixun
Published: January 2025

To enhance the utilization efficiency of wind and solar renewable energy in industrial parks, reduce operational costs, and optimize the charging experience for electric vehicle (EV) users, this paper proposes a real-time scheduling strategy based on the “Dual Electricity Price Reservation—Surplus Refund Without Additional Charges Mechanism” (DPRSRWAC). The strategy employs a Gaussian Mixture Model (GMM) to analyze EV users’ charging and discharging behaviors within the park, constructing a behavior prediction model. It introduces reservation, penalty, and ticket-grabbing mechanisms, combined with the Interval Optimization Method (IOM) and Particle Swarm Optimization (PSO), to dynamically solve the optimal reservation electricity price at each time step, thereby guiding user behavior effectively. Furthermore, linear programming (LP) is used to optimize the real-time charging and discharging schedules of EVs, incorporating reservation data into the generation-side model. The generation-side optimal charging and discharging behavior, along with real-time electricity prices, is determined using Dynamic Programming (DP). In addition, this study explicitly considers the battery aging cost associated with V2G operations and proposes a benefit model for EV owners in V2G mode, thereby incentivizing user participation and enhancing acceptance. A simulation analysis demonstrates that the proposed strategy effectively reduces park operation costs and user charging costs by 8.0% and 33.1%, respectively, while increasing the utilization efficiency of wind and solar energy by 19.3%. Key performance indicators are significantly improved, indicating the strategy’s economic viability and feasibility. This work provides an effective solution for energy management in smart industrial parks.
DeepOP: A Hybrid Framework for MITRE ATT&CK Sequence Prediction via Deep Learning and Ontology
Authors: Zhang Shuqin , Xue Xiaohang , Su Xinyu
Published: January 2025

As the Industrial Internet of Things (IIoT) increasingly integrates with traditional networks, advanced persistent threats (APTs) pose significant risks to critical infrastructure. Traditional Intrusion Detection Systems (IDSs) and Anomaly Detection Systems (ADSs) are often inadequate in countering sophisticated multi-step APT attacks. This highlights the necessity of studying attacker strategies and developing predictive models to mitigate potential threats. To address these challenges, we propose DeepOP, a hybrid framework for attack sequence prediction that combines deep learning and ontological reasoning. DeepOP leverages the MITRE ATT&CK framework to standardize attacker behavior and predict future attacks with fine-grained precision. Our framework’s core is a novel causal window self-attention mechanism embedded within a transformer-based architecture. This mechanism effectively captures local causal relationships and global dependencies within attack sequences, enabling accurate multi-step attack predictions. In addition, we construct a comprehensive dataset by extracting causally connected attack events from cyber threat intelligence (CTI) reports using ontological reasoning, mapping them to the ATT&CK framework. This approach addresses the challenge of insufficient data for fine-grained attack prediction and enhances the model’s ability to generalize across diverse scenarios. Experimental results demonstrate that the proposed model effectively predicts attacker behavior, achieving competitive performance in multi-step attack prediction tasks. Furthermore, DeepOP bridges the gap between theoretical modeling and practical security applications, providing a robust solution for countering complex APT threats.