bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemometric Methods—A Valuable Tool for Investigating the Interactions Between Antifungal Drugs (Including Antifungal Antibiotics) and Food
Authors: Wiesner-Kiełczewska Agnieszka , Zagrodzki Paweł , Gawalska Alicja , Paśko Paweł
Published: January 2025

Background/Objectives: Developing antifungal drugs with lower potential for interactions with food may help to optimize treatment and reduce the risk of antimicrobial resistance. Chemometrics uses statistical and mathematical methods to analyze multivariate chemical data, enabling the identification of key correlations and simplifying data interpretation. We used the partial least squares (PLS) approach to explore the correlations between various characteristics of oral antifungal drugs (including antifungal antibiotics) and dietary interventions, aiming to identify patterns that could inform the optimization of antifungal therapy. Methods: We analyzed 15 oral antifungal drugs, including azoles (8), antifungal antibiotics (4), antifungal antimetabolites (1), squalene epoxidase inhibitors (1), and glucan synthase inhibitors (1). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed PLS models with changes in the pharmacokinetic parameters (∆AUC, area under the curve; ∆Cmax, maximum drug concentration; and ∆Tmax, time to reach maximum drug concentration) after dietary intervention as the response parameters and eight groups of molecular descriptors (M1–M8) as the predictor parameters. We performed separate analyses for the different nutritional interventions. Results: In the final PLS model with food as an intervention, we effectively reduced the dimensionality of the dataset while retaining a substantial percentage of the original information (variance), as significant components explained 69.8% and 17.5% of the predictor and response parameter variances, respectively. The PLS model was significant because its components met the cross-validation criteria. We obtained six significant positive and negative correlations between the descriptors related to atoms and the postprandial ∆Tmax. Conclusions: The PLS method is valuable for investigating interactions between antifungal drugs (including antifungal antibiotics) and food. The correlations obtained can be used in drug modeling to predict interactions with dietary interventions based on the antifungal drug’s chemical structure. Incorporating chemometric techniques into the early drug development stages could facilitate the design of antifungal antibiotics and other antifungal agents with optimized absorption in the presence of dietary components.
Differences in User Perception of Artificial Intelligence-Driven Chatbots and Traditional Tools in Qualitative Data Analysis
Authors: Šumak Boštjan , Pušnik Maja , Kožuh Ines , Šorgo Andrej , Brdnik Saša
Published: January 2025

Qualitative data analysis (QDA) tools are essential for extracting insights from complex datasets. This study investigates researchers’ perceptions of the usability, user experience (UX), mental workload, trust, task complexity, and emotional impact of three tools: Taguette 1.4.1 (a traditional QDA tool), ChatGPT (GPT-4, December 2023 version), and Gemini (formerly Google Bard, December 2023 version). Participants (N = 85), Master’s students from the Faculty of Electrical Engineering and Computer Science with prior experience in UX evaluations and familiarity with AI-based chatbots, performed sentiment analysis and data annotation tasks using these tools, enabling a comparative evaluation. The results show that AI tools were associated with lower cognitive effort and more positive emotional responses compared to Taguette, which caused higher frustration and workload, especially during cognitively demanding tasks. Among the tools, ChatGPT achieved the highest usability score (SUS = 79.03) and was rated positively for emotional engagement. Trust levels varied, with Taguette preferred for task accuracy and ChatGPT rated highest in user confidence. Despite these differences, all tools performed consistently in identifying qualitative patterns. These findings suggest that AI-driven tools can enhance researchers’ experiences in QDA while emphasizing the need to align tool selection with specific tasks and user preferences.
Photoconductive Semiconductor Switches: Materials, Physics, and Applications
Authors: Meyers Vincent , Voss Lars , Flicker Jack D. , Rodriguez Luciano Garcia , Hjalmarson Harold P. , Lehr Jane , Gonzalez Nicolas , Pickrell Gregory , Ghandiparsi Soroush , Kaplar Robert
Published: January 2025

Photoconductive semiconductor switching (PCSS) devices have unique characteristics to address the growing need for electrically isolated, optically gated, picosecond-scale jitter devices capable of operating at high voltage, current, and frequency. The state of the art in material selection, doping, triggering, and system integration in PCSSs is presented. The material properties and doping considerations of GaN, GaAs, SiC, diamond, and β-Ga2O3 in the fabrication of PCSS devices are discussed. A review of the current understanding of the physics of the high-gain mode known as lock-on is presented.
Nuclear Intron Sequence Variation of the Bulinus globosus Complex (Mollusca: Planorbidae): Implications for Molecular Systematic Analyses
Authors: Tantrawatpan Chairat , Vaisusuk Kotchaphon , Tanga Chrysantus M. , Pilap Warayutt , Bunchom Naruemon , Andrews Ross H. , Thanchomnang Tongjit , Maleewong Wanchai , Saijuntha Weerachai
Published: January 2025

Urinary schistosomiasis is caused by the blood fluke Schistosoma haematobium, which is predominantly found in Africa. The freshwater snail Bulinus globosus is its main intermediate host. The species that make up the B. globosus group are genetically complex, and their taxonomic status remains controversial. Genetic variation, heterozygosity, and DNA recombination in B. globosus were examined using the mitochondrial cytochrome c oxidase subunit 1 (COI) and the intron 3 region of the arginine kinase gene (AkInt3). A total of 81 B. globosus snails were collected from three different localities in Kwale County, Kenya. Genomic diversity, heterozygosity, DNA recombination, and haplotype network were calculated using AkInt3 sequences. Low polymorphism in the COI sequence divided B. globosus into six haplotypes (C1–C6). However, AkInt3 sequencing studies showed high polymorphisms, classifying 81 B. globosus snails into 44 haplotypes (H1–H44). These haplotypes were separated into three haplogroups (I–III). AkInt3 sequence heterozygosity was also found. DNA recombination haplotypes between haplogroups were commonly found in heterozygous samples. AkInt3 sequence studies showed high levels of genetic polymorphism and heterozygosity, supporting its use as a genetic marker for elucidating the population genetics of B. globosus. Furthermore, our study showed that B. globosus populations in Kenya form a “species complex”.
Exploring the Revolutionary Impact of YAP Pathways on Physical and Rehabilitation Medicine
Authors: Pirri Carmelo
Published: January 2025

Cellular behavior is strongly influenced by mechanical signals in the surrounding microenvironment, along with external factors such as temperature fluctuations, changes in blood flow, and muscle activity, etc. These factors are key in shaping cellular states and can contribute to the development of various diseases. In the realm of rehabilitation physical therapies, therapeutic exercise and manual treatments, etc., are frequently employed, not just for pain relief but also to support recovery from diverse health conditions. However, the detailed molecular pathways through which these therapies interact with tissues and influence gene expression are not yet fully understood. The identification of YAP has been instrumental in closing this knowledge gap. YAP is known for its capacity to perceive and translate mechanical signals into specific transcriptional programs within cells. This insight has opened up new perspectives on how physical and rehabilitation medicine may exert its beneficial effects. The review investigates the involvement of the Hippo/YAP signaling pathway in various diseases and considers how different rehabilitation techniques leverage this pathway to aid in healing. Additionally, it examines the therapeutic potential of modulating the Hippo/YAP pathway within the context of rehabilitation, while also addressing the challenges and controversies that surround its use in physical and rehabilitation medicine.
The Construction of Heterothallic Strains of Komagataella kurtzmanii Using the I-SceI Meganuclease
Authors: Sokolova Daria D. , Akentyev Philipp I. , Petrova Kristina O. , Lyutova Lyudmila V. , Korzhenkov Aleksei A. , Gubaidullin Irek I. , Toshchakov Stepan V. , Kozlov Dmitry G.
Published: January 2025

The methylotrophic yeast Komagataella kurtzmanii belongs to the group of homothallic fungi that are able to spontaneously change their mating type by inversion of chromosomal DNA in the MAT locus region. As a result, natural and genetically engineered cultures of these yeasts typically contain a mixture of sexually dimorphic cells that are prone to self-diploidisation and spore formation accompanied by genetic rearrangements. These characteristics pose a significant challenge to the development of genetically stable producers for industrial use. In the present study, we constructed heterothallic strains of K. kurtzmanii, ensuring a constant mating type by unifying the genetic sequences in the active and silent MAT loci. To obtain such strains, we performed site-directed inactivation of one of the two yeast MAT loci, replacing its sequence with a selective HIS4 gene surrounded by I-SceI meganuclease recognition sites. We then used transient expression of the SCE1 gene, encoding a recombinant I-SceI meganuclease, to induce site-specific cleavage of HIS4, followed by damage repair by homologous recombination in mutant cells. As a result, heterothallic strains designated ‘Y-727-2(alpha)’ and ‘Y-727-9(a)’, which correspond to the α and a mating type, respectively, were obtained. The strains demonstrated a loss of the ability to self-diploidize. The results of PCR and whole genome analysis confirmed the identity of the contents of the MAT loci. Analysis of the genomes of the final strains, however, revealed a fusion of chromosome 3 and chromosome 4 in strain Y-727-2(alpha)-1. This finding was subsequently confirmed by pulsed-field gel electrophoresis of yeast chromosomes. However, the ability of the Y-727-2(alpha)-derived producers to efficiently secrete recombinant β-galactosidase was unaffected by this genomic rearrangement.
IL-6-Inducing Peptide Prediction Based on 3D Structure and Graph Neural Network
Authors: Cao Ruifen , Li Qiangsheng , Wei Pijing , Ding Yun , Bin Yannan , Zheng Chunhou
Published: January 2025

Interleukin-6 (IL-6) is a potent glycoprotein that plays a crucial role in regulating innate and adaptive immunity, as well as metabolism. The expression and release of IL-6 are closely correlated with the severity of various diseases. IL-6-inducing peptides are critical for the development of immunotherapy and diagnostic biomarkers for some diseases. Most existing methods for predicting IL-6-induced peptides use traditional machine learning methods, whose feature selection is based on prior knowledge. In addition, none of these methods take into account the three-dimensional (3D) structure of peptides, which is essential for their functional properties. In this study, we propose a novel IL-6-inducing peptide prediction method called DGIL-6, which integrates 3D structural information with graph neural networks. DGIL-6 represents a peptide sequence as a graph, where each amino acid is treated as a node, and the adjacency matrix, representing the relationships between nodes, is derived from the predicted residue contact graph of the peptide sequence. In addition to commonly used amino acid representations, such as one-hot encoding and position encoding, the pre-trained model ESM-1b is employed to extract amino acid features as node features. In order to simultaneously consider node weights and information updates, a dual-channel method combining Graph Attention Network (GAT) and Graph Convolutional Network (GCN) is adopted. Finally, the extracted features from both channels are merged for the classification of IL-6-inducing peptides. A series of experiments including cross-validation, independent testing, ablation studies, and visualizations demonstrate the effectiveness of the DGIL-6 method.
Cyclin G1 Regulates the Alveolarization in Models of Bronchopulmonary Dysplasia by Inhibiting AT2 Cell Proliferation
Authors: Xu Panpan , Zhuo Wanqing , Zhang Peipei , Chen Ying , Du Yue , Li Ying , Wang Yajuan
Published: January 2025

Disrupted neonatal lung alveologenesis often leads to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. The inhibition of type 2 alveolar (AT2) cell proliferation plays an important role in the arrest of alveologenesis. However, the mechanism of AT2 cell proliferation retardation in BPD is still not fully elucidated. The purpose of the present study was to explore the effects of cyclin G1 (CCNG1) on AT2 cell proliferation in hyperoxia-induced lung injury in neonatal mice. Our findings revealed that hyperoxia significantly reduced the proportion of AT2 cells in the lungs of neonatal mice and coincided with an upregulation of CCNG1 expression. Notably, this upregulation of CCNG1 was accompanied by an increase in Wnt signaling. We observed colocalization of CCNG1 and Wnt3a within AT2 cells in the hyperoxia group. Further analysis showed that inhibiting CCNG1 expression regressed the expression of Wnt signaling and enhanced cell proliferation. These results suggest that CCNG1 plays a pivotal role in suppressing AT2 cell proliferation, at least partly by counteracting the effects of Wnt signaling to modulate AT2 cell growth in the BPD model. Our findings contribute to a better understanding of the mechanisms underlying BPD.
Role of Epidural Electrode Stimulation in Three Patients with Incomplete AIS D Spinal Cord Injury
Authors: Chen Yu-Chen , Huang Xiang-Ling , Cheng Hung-Yu , Wu Ciou-Chan , Wu Ming-Yung , Yan Lian-Cing , Chen Shin-Yuan , Tsai Sheng-Tzung , Lin Shinn-Zong
Published: January 2025

Background/Objectives: To determine whether epidural electrical stimulation (EES) improves sensory recovery and walking function in patients with chronic spinal cord injury (SCI) with a grade on the American Spinal Cord Injury Association impairment scale (AIS) of C or D at the cervical level. Methods: Three individuals with cervical-level chronic AIS D SCI were enrolled in the study. The mean injury duration and age were 4.8 ± 4.5 (range: 1.5–10) and 56.7 ± 9 years, respectively. The participants received personalized electrical stimulation for 36 weeks and were evaluated for their SCI characteristics, the result of an AIS assessment according to the lower extremity sensorimotor scale, their muscle activity, and preoperative walking ability parameters, initially as well as at weeks 8 and 36 of the EES intervention. Results: Participants receiving EES significantly increased the muscle activity in most lower limb muscles. Regarding the AIS assessment of the lower extremities, one participant fully regained a light touch sensation, while two fully recovered their pinprick sensation (AIS sensory scores increased from 14 to 28). One participant achieved a full motor score, whereas the others’ scores increased by 19 and 7 points. Compared with preoperative gait parameters, two participants showed improvements in their walking speed and cadence. Walking symmetry, an important parameter for assessing walking function, improved by 68.7%, 88%, and 77% in the three participants, significantly improving the symmetry index (p = 0.003). Conclusions: Thus, EES may be an effective strategy for sensory impairment recovery, as well as muscular activity and strength improvement. These findings may facilitate stable walking in subjects with chronic incomplete SCI, but larger clinical trials are warranted. Clinical trial: NCT05433064.
Differential Role of NKG2A/HLA-E Interaction in the Outcomes of Bladder Cancer Patients Treated with M. bovis BCG or Other Therapies
Authors: Ruiz-Lorente Inmaculada , Gimeno Lourdes , López-Abad Alicia , López Cubillana Pedro , Fernández Aparicio Tomás , Asensio Egea Lucas Jesús , Moreno Avilés Juan , Doñate Iñiguez Gloria , Guzmán Martínez-Valls Pablo Luis , Server Gerardo , Ferri Belén , Campillo José Antonio , Martínez-Sánchez María Victoria , Minguela Alfredo
Published: January 2025

Background: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette–Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. Methods: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B −21M/T dimorphism (NKG2A ligands). Results: The HLA-B −21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, p = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, p = 0.131) survival in other treatments. The HLA-B −21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, p = 0.01) and the OS (HR = 2.059, p = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56bright, fewer KIR2DL1/L2+ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. Conclusions: The HLA-B −21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients.
Understanding the Spectrum of Mild Clinical Outcomes and Novel Findings in Arterial Tortuosity Syndrome Among Qatari Patients: Implications of SLC2A10 Mutation
Authors: Rahmath Muhammed Riyas K. , Ibrahim Haytham , Faiyaz-Ul-Haque Muhammad , Nawaz Zafar , Zitoun Ahmad , Hussein Ahmed , Sadek Ahmed , El-Menyar Ayman , Kamal Reema , Al-Thani Hassan , Sher Gulab
Published: January 2025

Background/Objectives: Arterial Tortuosity Syndrome (ATS) is a rare, autosomal recessive connective tissue disorder characterized by arterial twists, abnormal bulges, constriction, and tears. Patients have distinctive features and disease manifestations. The syndrome’s full clinical spectrum and course remain incompletely understood. Methods: We sought to review the medical records of Qatari patients who had ATS. The cohort study included 21 patients who were genetically confirmed by mutations in the SLC2A10 gene. Results: The study revealed that the NM_030777.4(SLC2A10):c.243C>G (p.Ser81Arg) mutation in SLC2A10 leads to mild outcomes of no mortality and less morbidity. Novel features such as a flat philtrum, bulbous noses, bilateral nasolacrimal duct obstruction, allergic conjunctivitis, latent nystagmus, café au lait spots, eczema, dermatitis, allergic reactions, bilateral temporomandibular joint cysts, bilateral syndactyly (toes), parapelvic cysts, kidney malrotation, vesicoureteral reflux, and nephrolithiasis were identified in our cohort. Furthermore, rare features previously documented in a limited number of patients, including leg length discrepancy, epilepsy, and migraine headaches, were also observed in our cohort. Conclusions: Our data contributes new insights into the life course of ATS in Qatari patients. These findings underscore the importance of effective education strategies through repeated counseling aimed at preventing cousin marriage and the syndrome within the cohort.
Redox Metabolism and Autonomic Regulation During Aging: Can Heart Rate Variability Be Used to Monitor Healthy Longevity?
Authors: Yelisyeyeva Olha , Kaminskyy Danylo , Semen Marta , Chelpanova Ilona , Semen Khrystyna O.
Published: January 2025

The functionality of redox metabolism is frequently named as an important contributor to the processes of aging and anti-aging. Excessive activation of free radical reactions accompanied by the inability of the antioxidant defense (AOD) mechanisms to control the flow of the reactive oxygen species (ROS) leads to the persistence of oxidative stress, hypoxia, impaired mitochondrial energy function and reduced ATP potential. From a long-term perspective, such changes contribute to the development of chronic diseases and facilitate aging. In turn, preconditioning of a biosystem with small doses of stressful stimuli might cause mobilization of the mechanisms of AOD and control an excessive flow of ROS, which supports optimal functioning of the redox reactions. Those mechanisms are of crucial importance for anti-aging and are also known as a eustress or hormetic response. To ensure continuous support of mild pro-oxidant activity in a metabolic system, close monitoring and timely corrections preventing the development of excessive ROS production are required. The paper introduces the potential of heart rate variability (HRV) as a biomarker of functional and metabolic reserves and a tool to measure stress resilience during aging. The practical approaches to interpretation of HRV are provided based on total power, changes in total power in response to an orthostatic test and activities of all spectral components. It is suggested that the complex of those parameters can reflect the depth of oxidative stress and may be used to guide lifestyle interventions and promote active longevity.
MSBKA: A Multi-Strategy Improved Black-Winged Kite Algorithm for Feature Selection of Natural Disaster Tweets Classification
Authors: Mu Guangyu , Li Jiaxue , Liu Zhanhui , Dai Jiaxiu , Qu Jiayi , Li Xiurong
Published: January 2025

With the advancement of the Internet, social media platforms have gradually become powerful in spreading crisis-related content. Identifying informative tweets associated with natural disasters is beneficial for the rescue operation. When faced with massive text data, choosing the pivotal features, reducing the calculation expense, and increasing the model classification performance is a significant challenge. Therefore, this study proposes a multi-strategy improved black-winged kite algorithm (MSBKA) for feature selection of natural disaster tweets classification based on the wrapper method’s principle. Firstly, BKA is improved by utilizing the enhanced Circle mapping, integrating the hierarchical reverse learning, and introducing the Nelder–Mead method. Then, MSBKA is combined with the excellent classifier SVM (RBF kernel function) to construct a hybrid model. Finally, the MSBKA-SVM model performs feature selection and tweet classification tasks. The empirical analysis of the data from four natural disasters shows that the proposed model has achieved an accuracy of 0.8822. Compared with GA, PSO, SSA, and BKA, the accuracy is increased by 4.34%, 2.13%, 2.94%, and 6.35%, respectively. This research proves that the MSBKA-SVM model can play a supporting role in reducing disaster risk.
Integration of Functional Materials in Photonic and Optoelectronic Technologies for Advanced Medical Diagnostics
Authors: Thanjavur Naveen , Bugude Laxmi , Kim Young-Joon
Published: January 2025

Integrating functional materials with photonic and optoelectronic technologies has revolutionized medical diagnostics, enhancing imaging and sensing capabilities. This review provides a comprehensive overview of recent innovations in functional materials, such as quantum dots, perovskites, plasmonic nanomaterials, and organic semiconductors, which have been instrumental in the development of diagnostic devices characterized by high sensitivity, specificity, and resolution. Their unique optical properties enable real-time monitoring of biological processes, advancing early disease detection and personalized treatment. However, challenges such as material stability, reproducibility, scalability, and environmental sustainability remain critical barriers to their clinical translation. Breakthroughs such as green synthesis, continuous flow production, and advanced surface engineering are addressing these limitations, paving the way for next-generation diagnostic tools. This article highlights the transformative potential of interdisciplinary research in overcoming these challenges and emphasizes the importance of sustainable and scalable strategies for harnessing functional materials in medical diagnostics. The ultimate goal is to inspire further innovation in the field, enabling the creation of practical, cost-effective, and environmentally friendly diagnostic solutions.
A Novel Method for Predicting Urban Residential Quality Distribution Based on Multi-Interest Consideration
Authors: Ren Jiawen , Zhou Xin , An Jingjing , Shi Xing , Jin Xing , Hong Tianzhen , Yan Da
Published: January 2025

Simulating and predicting urban patterns enables evidence-based decision-making for urban planners. Given limited resources, understanding how to improve urban residential quality and rationally plan the distribution of different quality levels warrants further study. Using cellular automata (CA) and agent-based modules, this study proposes a multi-stakeholder residential quality distribution model to analyze the future quality distribution of residential buildings under different scenarios. The proposed model comprises two modules: a CA module predicting an urban functional layout model and an agent-based module predicting residential quality distribution. The CA module develops the future functional layout of the city, upon which the multiple interests of the government, developers, and residents are taken as constraints by the agent-based module to predict residential quality distribution. The proposed model was applied as a case study to Guanxian County in Shandong Province, China. Three scenario analyses were conducted: a free development scenario, a government macro-regulation scenario, and a scenario with an adjusted preference value for residential quality. The results show that the residential quality distribution model predictions make it possible to align residential quality with residents’ needs in different scenarios; hence, unreasonable distribution characteristics can be explored to develop effective improvement measures.
Optimization of Covariance Matrices of Kalman Filter with Unknown Input Using Modified Directional Bat Algorithm
Authors: Liu Lijun , Yin Chang , Su Yonghui , Lin Yinghai , Lei Ying
Published: January 2025

The proper selection of the model error covariance matrix and the measurement noise covariance matrix of Kalman filter is an optimization problem. Some scholars have studied this, but there is relatively little research on the selection of the two covariance matrices for Kalman filters with an unknown input. Recently, the authors proposed a modified directed bat algorithm (MDBA) which introduces the best historical location of individuals and the elimination strategy to effectively prevent falling into local optimal solution. So, two methods are proposed in this paper to optimize the model error covariance matrix and measurement noise covariance matrix of Kalman filter with unknown inputs (KF-UI) and extended Kalman filter with unknown inputs (EKF-UI) by MDBA, respectively. The objective functions are constructed using the measurement vectors and the corresponding estimated values, and MDBA is adopted to optimize the two covariance matrices of KF-UI and EKF-UI. To validate the effectiveness of proposed methods, two simple structure examples and a benchmark example are adopted. The influence of structural parameter uncertainties on KF-UI is also considered. The result shows that the MDBA-optimized KF-UI has a strong convergence and can take into account the effect of parameter uncertainties. Then, the effectiveness of the proposed MDBA-optimized EKF-UI method is validated by comparing it with EKF-UI with empirically selected covariance values through trial-and-error. The identification results showed that the proposed methods achieved better identification accuracy and enhanced convergence compared to KF-UI and EKF-UI with empirical covariance values.
Molybdenum Telluride-Promoted BiOCl Photocatalysts for the Degradation of Sulfamethoxazole Under Solar Irradiation: Kinetics, Mechanism, and Transformation Products
Authors: Ioannidi Alexandra A. , Kouvelis Konstantinos , Ntourmous Gkizem , Petala Athanasia , Mantzavinos Dionissios , Antonopoulou Maria , Frontistis Zacharias
Published: January 2025

This work examines the solar photocatalytic degradation of the antibiotic sulfamethoxazole (SMX) using molybdenum telluride (MoTe2)-promoted bismuth oxychloride (BiOCl). Different loadings of molybdenum telluride in the 0–1% range on BiOCl were synthesized and evaluated. Although the presence of MoTe2 did not alter either the adsorption capacity or the energy gap of BiOCl, the synthesized photocatalyst demonstrated higher photocatalytic activity due to the enhanced separation of photogenerated pairs. The 0.5MoTe2/BiOCl photocatalyst achieved a kinetic constant nearly 2.8 times higher than that of pure BiOCl, leading to the elimination of 500 μg/L SMX within 90 min. The system’s performance was enhanced under neutral to acidic conditions and lower SMX concentrations. Based on experiments with radical scavengers, photogenerated holes appeared to be the dominant species, with the contribution of reactive species following the order h+>O2•−/e−>1O2>HO•. Interestingly, in different water matrices, photocatalytic activity was not diminished and even increased by 20%, likely because of the action of photogenerated holes and the selectivity of secondary generated radicals. The photocatalyst retained > 90% of its activity after three sequential experiments. Finally, four transformation products from SMX photodegradation were identified via UHPLC-TOF-MS, and a degradation pathway is proposed.
IFN-τ Maintains Immune Tolerance by Promoting M2 Macrophage Polarization via Modulation of Bta-miR-30b-5p in Early Uterine Pregnancy in Dairy Cows
Authors: Feng Xinyu , Yang Cheng , Wang Ting , Zhang Jinxin , Zhou Han , Ma Bin , Xu Ming , Deng Ganzhen
Published: January 2025

Pregnancy failure in the first trimester of cows significantly impacts the efficiency of the dairy industry. As a type I interferon exclusively to ruminants, IFN-τ plays a key role in maternal recognition and immune tolerance of fetuses. Macrophages are the most common immune cells within the ruminant endometrium. Nevertheless, deeply analyzing the mechanisms of IFN-τ regulating macrophage polarization still needs further study. In this study, a notable decline of bta-miR-30b-5p expression via the increase of SOCS1 was observed in uterine tissues of pregnant cows. We then confirmed that the 3′UTR of SOCS1 was to be directly targeted by bta-miR-30b-5p. After that, we demonstrated that this obviously promoted the bovine macrophages (BoMac) polarized to M2 through enhancing SOCS1 expression with the treatment of IFN-τ. Furthermore, we found that SOCS1 restrained the expression of the key proteins p65 and p-P65 in the NF-κB pathway. Causing, the wide range of cross-species activities of IFN-τ, therefore we established a pregnant mouse model for the future confirmation of the above mechanism. The results verified that IFN-τ significantly improved this mechanism and maintained normal pregnancy status in mice, but miR-30b-5p significantly reduced the M2 polarization by inhibiting SOCS1, which activated the NF-κB signaling pathway, and then leading to the failure of embryo implantation. All these results indicated that IFN-τ can regulate immune tolerance during pregnancy by promoting M2 macrophage polarization through inhibiting bta-miR-30b-5p targeting SOCS1 to deactivate the NF-κB signaling pathway.
Alpha-1 Antitrypsin as a Regulatory Protease Inhibitor Modulating Inflammation and Shaping the Tumor Microenvironment in Cancer
Authors: Xiang Siyu , Yang Liu , He Yun , Ding Feng , Qiao Shuangying , Su Zonghua , Chen Zheng , Lu Aiping , Li Fangfei
Published: January 2025

Alpha-1 antitrypsin (AAT) is a key serine protease inhibitor for regulating proteases such as neutrophil elastase. AAT restrains the pulmonary matrix from enzymatic degradation, and a deficiency in AAT leads to inflammatory tissue damage in the lungs, resulting in chronic obstructive pulmonary disease. Due to the crucial biological function of AAT, the emerging research interest in this protein has shifted to its role in cancer-associated inflammation and the dynamics of the tumor microenvironment. However, the lack of comprehensive reviews in this field hinders our understanding of AAT as an essential immune modulator with great potential in cancer immunotherapy. Therefore, in this review, we have elucidated the pivotal roles of AAT in inflammation and the tumor microenvironment, including the structure and molecular properties of AAT, its molecular functions in the regulation of the inflammatory response and tumor microenvironment, and its clinical implications in cancer including its diagnosis, prognosis, and therapeutic intervention. This review seeks to bridge the gap in the understanding of AAT between inflammatory diseases and cancer, and to foster deeper investigations into its translational potential in cancer immunotherapy in the future.
Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy
Authors: Ahn Eun Hee , Park Jae-Bong
Published: January 2025

Amyloid-β peptide (Aβ) is a critical cause of Alzheimer’s disease (AD). It is generated from amyloid precursor protein (APP) through cleavages by β-secretase and γ-secretase. γ-Secretase, which includes presenilin, is regulated by several stimuli. Tau protein has also been identified as a significant factor in AD. In particular, Tau phosphorylation is crucial for neuronal impairment, as phosphorylated Tau detaches from microtubules, leading to the formation of neurofibrillary tangles and the destabilization of the microtubule structure. This instability in microtubules damages axons and dendrites, resulting in neuronal impairment. Notably, Aβ is linked to Tau phosphorylation. Another crucial factor in AD is neuroinflammation, primarily occurring in the microglia. Microglia possess several receptors that bind with Aβ, triggering the expression and release of an inflammatory factor, although their main physiological function is to phagocytose debris and pathogens in the brain. NF-κB activation plays a major role in neuroinflammation. Additionally, the production of reactive oxygen species (ROS) in the microglia contributes to this neuroinflammation. In microglia, superoxide is produced through NADPH oxidase, specifically NOX2. Rho GTPases play an essential role in regulating various cellular processes, including cytoskeletal rearrangement, morphology changes, migration, and transcription. The typical function of Rho GTPases involves regulating actin filament formation. Neurons, with their complex processes and synapse connections, rely on cytoskeletal dynamics for structural support. Other brain cells, such as astrocytes, microglia, and oligodendrocytes, also depend on specific cytoskeletal structures to maintain their unique cellular architectures. Thus, the aberrant regulation of Rho GTPases activity can disrupt actin filaments, leading to altered cell morphology, including changes in neuronal processes and synapses, and potentially contributing to brain diseases such as AD.
Traumatic Brain Injury Promotes Neurogenesis and Oligodendrogenesis in Subcortical Brain Regions of Mice
Authors: Astakhova Olga , Ivanova Anna , Komoltsev Ilia , Gulyaeva Natalia , Enikolopov Grigori , Lazutkin Alexander
Published: January 2025

Traumatic brain injury (TBI) is one of the major causes of severe neurological disorders and long-term dysfunction in the nervous system. Besides inducing neurodegeneration, TBI alters stem cell activity and neurogenesis within primary neurogenic niches. However, the fate of dividing cells in other brain regions remains unclear despite offering potential targets for therapeutic intervention. Here, we investigated cell division and differentiation in non-neurogenic brain regions during the acute and delayed phases of TBI-induced neurodegeneration. We subjected mice to lateral fluid percussion injury (LFPI) to model TBI and analyzed them 1 or 7 weeks later. To assess cellular proliferation and differentiation, we administered 5-ethinyl-2′-deoxyuridine (EdU) and determined the number and identity of dividing cells 2 h later using markers of neuronal precursors and astro-, micro-, and oligodendroglia. Our results demonstrated a significant proliferative response in several brain regions at one week post-injury that notably diminished by seven weeks, except in the optic tract. In addition to active astro- and microgliosis, we detected oligodendrogenesis in the striatum and optic tract. Furthermore, we observed trauma-induced neurogenesis in the striatum. These findings suggest that subcortical structures, particularly the striatum and optic tract, may possess a potential for self-repair through neuronal regeneration and axon remyelination.
Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in Leptin-Deficient Rats
Authors: Xin Xiaoming , Ni Yaohua , Wang Jing , Wu Fenglin , Liu Meichen , Wu Lingjuan , Dai Jiaxing , Wu Chenglin , Song Xiaolei , Zhang Wang , Yang Guangrui , Shen Ruling , Zhu Xianmin
Published: January 2025

Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized Lep∆I14/∆I14 rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models.
Analysis of Salivary Cytokines in Retinopathy of Prematurity
Authors: Wu Hwa-Shiu , Huang Hsin-Chun , Chen I-Lun
Published: January 2025

Background/Objectives: This cohort study aimed to establish a correlation between salivary cytokines and retinopathy of prematurity (ROP) in premature neonates. Additionally, we sought to identify a minimally invasive method for cytokine detection in this population. Methods: We recruited premature neonates born at less than 34 weeks gestational age (GA), with no history of maternal or neonatal infections. Salivary samples were collected on their first (D1) and seventh (D7) days of life, and cytokine levels were measured using the MILLPLEXMAP Human multiplex assay. Results: A total of 125 neonates were included in the study, categorized into two groups based on the severity of ROP: None to Mild and Moderate to Severe. The salivary levels of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α on D1 and D7 were significantly higher in the Moderate to Severe ROP group compared to the None to Mild ROP group (p = 0.005, 0.004, 0.026, 0.018, 0.001, 0.007, 0.025, and 0.002, respectively). After adjusting for GA, the levels of IL-6 and VEGF on D7 were significantly elevated in the Moderate to Severe ROP group compared to the None to Mild ROP group (p = 0.024 and 0.016, respectively). Conclusions: This study establishes a novel, non-invasive method for the early prediction of ROP in premature neonates by correlating salivary cytokine levels in early life with the subsequent development of ROP.
Notoginsenoside R1 Attenuates H/R Injury in H9c2 Cells by Maintaining Mitochondrial Homeostasis
Authors: Xu Yuanbo , Wang Piao , Hu Ting , Ning Ke , Bao Yimin
Published: January 2025

Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia–reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I–V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission–fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes.
SAR Miniatures: Physical Scale Models as Immersive Prototypes for Spatially Augmented Environments
Authors: Martinez Gasca Omar , Van Dorpe Lucas , Dewit Ivo , Van Campenhout Lukas
Published: January 2025

This paper explores the use of physical scale models as immersive prototypes in the design and development of Spatial Augmented Reality (SAR) environments. SAR integrates digital projections with physical spaces, offering benefits for spatial reasoning and coordinated activities. However, designing SAR systems at full scale presents challenges in testing and refinement due to their complex physical–digital properties. To address this, we developed augmented miniature environments for two case studies: an in-store retail navigation system and a manufacturing assembly process. These models effectively materialized SAR’s most important experiential qualities at a manageable scale, enabling the exploration of spatial relationships, coordinated user activity, and system functionality in a tangible and accessible way. The miniatures facilitated collaborative design, providing a shared medium for stakeholders to visualize and experiment with SAR applications. This paper presents augmented miniatures as effective tools for SAR design that foster creative exploration and communication, and highlights opportunities for future research in combining these models with digital prototyping technologies.
Predictive Utility of the HALP and Modified HALP Score for the Assessment of Operative Complications in Patients Undergoing Laparoscopic Cholecystectomy for Acute Cholecystitis
Authors: Keskin Yasemin , Sevinç Hakan , Hazinedaroğlu Selçuk Mevlüt , Morkavuk Şevket Barış , Ersöz Şiyar
Published: January 2025

Background and Objectives: The aim of the present study was to calculate HALP and modified HALP scores for patients diagnosed with acute cholecystitis (AC) and to determine the predictive utility of these scores for surgical timing and morbidity in patients who underwent surgery for AC. Materials and Methods: This study included data from 641 patients who underwent surgery for AC between January 2010 and May 2023. The HALP score was calculated using the formula hemoglobin (g/L) × albumin (g/L) × lymphocyte (109/L)/platelets (109/L). The modified HALP score was calculated using the formula hemoglobin (g/L) × albumin (g/L) × lymphocyte (109/L) × platelets (109/L). Results: The mean HALP score was 46.81, and the mean modified HALP score was 2,758,401.21. Laparoscopic cholecystectomy (LC) was successfully completed in 582 (90.8%) patients. When examining the relationship between HALP and modified HALP scores and the procedure type, a statistically significant difference was found in the distribution of median HALP and modified HALP scores between the LC and laparoscopic and open cholecystectomy (LTOC) groups. For patients with a HALP score < 34.43 and modified HALP score < 2,077,019, the likelihood of conversion to open surgery increased, with a sensitivity of 65.5% vs. 58.8% and a specificity of 66.1% vs. 59.3%. In patients who underwent surgery, there was a significant difference in the LTOC between the HALP score and modified HALP score cut-off groups (p < 0.001 and, p = 0.007). Conclusions: Evaluation of the HALP score is a promising and valuable assessment method for designing appropriate treatment and management strategies for patients with AC.