bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of E-Cigarette (e-cig) Aerosols on Mutagenesis in Selected Organs in a C57 lacI (BigBlueTM) Mouse Model
Authors: Chhaya Dweet , Gress Merna , Raja Amna , Kosinska Wieslawa , Gordon Terry , Zelikoff Judith , Guttenplan Joseph B.
Published: December 2024

The objective of this study is to investigate the potential mutagenic effects of the exposure of mice to aerosols produced from the component liquids of an electronic nicotine delivery system (ENDS). The use of electronic cigarettes (e-cigs) and ENDSs has increased tremendously over the past two decades. From what we know to date, ENDSs contain much lower levels of known carcinogens than tobacco smoke. While conventional tobacco smoke is a well-established mutagen, little is known about the mutagenicity of ENDS aerosols. Here, we report the mutagenic effects of a 3-month whole body exposure of C57 lacI mice (BigBlueTM) to filtered air (AIR) or ENDS aerosols in several tissues. Aerosols were generated from a 50/50 vegetable glycerin (VG)/propylene glycol (PG) mixture with and without nicotine. The results revealed that in the lung, bladder urothelial tissue, and tongue, mutagenesis was significantly greater in the VG/PG/nicotine group than in the AIR group. In all organs except the bladder, mutagenesis in the VG/PG only group was similar to those exposed to AIR. In the bladder, mutagenesis in the VG/PG group was elevated compared to that in the AIR group. In the liver, mutagenesis was modestly elevated in the VG/PG/nicotine group, but the elevation failed to reach statistical significance. Overall, there were no consistent differences in mutagenesis between the sexes. The results of this study suggest that exposure to e-cig aerosols containing nicotine represents a risk factor for carcinogenesis in several organ systems, and exposure to VG/PG alone may be a risk factor for bladder cancer.
A Machine Learning Classification Model for Gastrointestinal Health in Cancer Survivors: Roles of Telomere Length and Social Determinants of Health
Authors: Han Claire J. , Ning Xia , Burd Christin E. , Tounkara Fode , Kalady Matthew F. , Noonan Anne M. , Von Ah Diane
Published: December 2024

Background: Gastrointestinal (GI) distress is prevalent and often persistent among cancer survivors, impacting their quality of life, nutrition, daily function, and mortality. GI health screening is crucial for preventing and managing this distress. However, accurate classification methods for GI health remain unexplored. We aimed to develop machine learning (ML) models to classify GI health status (better vs. worse) by incorporating biological aging and social determinants of health (SDOH) indicators in cancer survivors. Methods: We included 645 adult cancer survivors from the 1999–2002 NHANES survey. Using training and test datasets, we employed six ML models to classify GI health conditions (better vs. worse). These models incorporated leukocyte telomere length (TL), SDOH, and demographic/clinical data. Results: Among the ML models, the random forest (RF) performed the best, achieving a high area under the curve (AUC = 0.98) in the training dataset. The gradient boosting machine (GBM) demonstrated excellent classification performance with a high AUC (0.80) in the test dataset. TL, several socio-economic factors, cancer risk behaviors (including lifestyle choices), and inflammatory markers were associated with GI health. The most significant input features for better GI health in our ML models were longer TL and an annual household income above the poverty level, followed by routine physical activity, low white blood cell counts, and food security. Conclusions: Our findings provide valuable insights into classifying and identifying risk factors related to GI health, including biological aging and SDOH indicators. To enhance model predictability, further longitudinal studies and external clinical validations are necessary.
Associations of Plant-Based Foods, Animal Products, and Selected Sociodemographic Factors with Gastroesophageal Reflux Disease Risk
Authors: El Shikieri Ahlam , Eltahir Zakaria , Aman Abdulmannan , Alhadramy Mohamad
Published: December 2024

Background: Diet influences the symptoms of gastroesophageal reflux disease (GERD). Plant-based diets rich in vegetables, fruits, legumes, seeds, and nuts may reduce inflammation and improve gut health, while high-fat foods may worsen symptoms. Objective: We examined the association between plant-based and animal-based foods, selected demographic characteristics, and the likelihood of GERD in Al Madinah Al Munawarah, Saudi Arabia. Method: A cross-sectional study using the GerdQ tool assessed the GERD likelihood among 303 adults. Dietary diversity scores were used to assess the quality of their diet. quality. Results: The participants were predominantly women (68.6%) and had low education levels (88.4%). Cereals were the most consumed plant-based foods, while vitamin A-rich fruits and vegetables were the least consumed. There was significant variation in the consumption of legumes, nuts, seeds, and milk and milk products among the GERD groups. The participants with a 50% GERD likelihood had the highest consumption (34.5%), followed by the 89% likelihood group (21.4%) and the 79% likelihood group (14.5%). The lowest consumption of milk and milk products was among those with an 89% GERD likelihood who also consumed more organ meat. In addition, GERD likelihood was inversely associated with age (r = −0.153; p = 0.008). The likelihood of GERD was negatively correlated with the intake of legumes, nuts, and seeds (r = −0.163; p = 0.005). Furthermore, the intake of cereals and tubers (r = 0.114; p = 0.047) and legumes, nuts, and seeds (r = 0.231; p = 0.0001) increased significantly with education. Conclusion: GERD prevention programs should target women, those with a low education level, and individuals consuming fewer plant-based foods and more organ meats.
Does Urban Polycentric Structure Improve Carbon Emission Efficiency? A Spatial Panel Data Analysis of 279 Cities in China from 2012 to 2020
Authors: Zhang Shihan , Xue Yanxin , Jin Shuzhen , Chen Zhenghong , Cheng Suiying , Wang Wei
Published: December 2024

Urban spatial structure, shaped by human intervention in the natural environment, impacts the functional space and socioeconomic efficiency of cities. Against this backdrop, this study investigates the linkage between urban spatial structure (USS) and carbon emission efficiency (CEE) in China from 2012 to 2020. This paper employs a nine-year dataset and spatial econometric models involving 279 prefectural cities in China. The study innovatively employs the Herfindahl index and the super-efficiency SBM model to evaluate the level of polycentric urban structure and CEE in these cities. It further explores the trends in spatial evolution and relevant characteristics of these factors. Additionally, the study applies the SDM to explore the spillover effect of urban polycentric structure on CEE. The study makes innovative use of the Herfindahl index and the super-efficiency SBM model to evaluate the level of polycentric urban structure and CEE in these cities, further exploring the trends in spatial evolution and relevant characteristics of these factors. Additionally, it applies the SDM to explore the spillover effect of urban polycentric structure on CEE. Robustness tests are carried out to confirm the findings. The results confirm that a polycentric structure significantly enhances carbon emission efficiency within a city. However, it adversely affects neighboring cities by reducing their carbon emission efficiency through negative spatial spillover effects. The results verify that a polycentric structure significantly enhances carbon emission efficiency within a city. However, it has an adverse impact on neighboring cities by reducing their carbon emission efficiency through negative spatial spillover effects.
The Diagnostic Value of Cerebrospinal Fluid Neurogranin in Neurodegenerative Diseases
Authors: Krawczuk Daria , Mroczko Piotr , Winkel Izabela , Mroczko Barbara
Published: December 2024

Synaptic pathology is crucial in neurodegenerative diseases (NDs), and numerous studies show a correlation between synaptic proteins and the rate of cognitive decline in Alzheimer’s disease, Parkinson’s disease, dementia, and Creutzfeldt–Jacob’s disease. Due to the fact that altered synaptic function is considered a core feature of the pathophysiology of neurodegenerative disorders, synaptic proteins, such as neurogranin, may serve as a biomarker of these diseases. Neurogranin is a postsynaptic protein located in the cell bodies and dendrites of neurons, foremost in the cerebral cortex, hippocampus, and striatum. It has been established that neurogranin is involved in synaptic plasticity and long-term potentiation. Literature data indicate that cerebrospinal fluid neurogranin may be useful as a biomarker for more accurate diagnosis and prognosis of neurodegenerative diseases. In this review, the diagnostic value of cerebrospinal fluid neurogranin in most common neurodegenerative diseases is examined.
Synthesis of Novel Benzofuran Spiro-2-Pyrrolidine Derivatives via [3+2] Azomethine Ylide Cycloadditions and Their Antitumor Activity
Authors: Pan Bowen , Wang Tao , Zheng Liangliang , Dong Zhangchao , Liu Lijuan , Liu Xiongwei , Feng Tingting , Zhou Ying , Shi Yang
Published: December 2024

A synthetic strategy of a three-component spiro-pyrrolidine compound based on benzofuran via an [3+2] azomethine ylide cycloaddition reaction is reported herein. Under mild optimal conditions, this reaction can quickly produce potentially bioactive compounds with a wide range of substrates, high yield, and simple operation. The desired products were obtained with a yield of 74–99% and a diastereomeric ratio (dr) of >20:1. Subsequently, the inhibitory effects of the compounds on the cell viability of the human cancer cell line HeLa and mouse cancer cell line CT26 were evaluated. Compounds 4b (IC50 = 15.14 ± 1.33 µM) and 4c (IC50 = 10.26 ± 0.87 µM) showed higher antiproliferative activities against HeLa cells than cisplatin (IC50 = 15.91 ± 1.09 µM); compounds 4e (IC50 = 8.31 ± 0.64 µM) and 4s (IC50 = 5.28 ± 0.72 µM) exhibited better inhibitory activities against CT26 cells than cisplatin (IC50 = 10.27 ± 0.71 µM). The introduction of electron-donating substituents was beneficial to the inhibitory activities against cancer cells. Molecular docking simulations revealed that 4e and 4s may exert corresponding bioactivities by binding to antitumor targets through hydrogen bonds, providing a new approach for discovering spiro-heterocyclic antitumor drugs.
Extended Photoperiod Facilitated the Restoration of the Expression of GH-IGF Axis Genes in Submerged Rainbow Trout (Oncorhynchus mykiss)
Authors: Dong Kang , Hou Zhishuai , Li Zhao , Xu Yuling , Gao Qinfeng
Published: December 2024

Salmonids, classified as physostomous fish, maintain buoyancy by ingesting air to inflate their swim bladders. Long-term submergence has been shown to cause body imbalance and reduced growth performance in these fish. Previous studies have demonstrated that extended photoperiod can promote growth in salmonids. This study aimed to investigate the regulatory effects of prolonged lighting on the growth of submerged rainbow trout (Oncorhynchus mykiss) by examining the transcriptional expression of genes in the growth hormone (GH)-insulin-like growth factor (IGF) axis. Rainbow trout were individually reared in one of the six environments, defined by the combination of three photoperiods (0L:24D, 12L:12D, and 24L:0D) and two spatial rearing modes (routine and submerged), for 16 weeks. We compared the growth performance of rainbow trout in different environments and further analyzed the transcription profiles and correlations of GH-IGF axis genes in the brain, liver, and muscle. The findings of this study were as follows: growth performance of rainbow trout gradually increased with photoperiod duration. Specifically, final body weight (FBW) and specific growth rate (SGR) increased, while feed conversion ratio (FCR) decreased. Extended photoperiod partially mitigated the adverse effects of long-term submergence on rainbow trout growth. Under 24L:0D photoperiod conditions, growth performance (FBW, SGR, and FCR) in submerged and routine rainbow trout was more closely aligned compared to 0L:24D and 12L:12D photoperiod conditions. In response to variations in the photoperiod, GH-IGF axis genes of rainbow trout exhibited significant transcriptional differences, particularly between treatments with 0L:24D and 24L:0D light exposure. An extended photoperiod facilitated the restoration of the expression of GH-IGF axis genes in submerged rainbow trout towards routine levels, including the up-regulation of sst and sstr2 genes in the brain. Correlation analysis implied differentiation of physiological functions of ghr and igfbp paralogs. This study provided insights into the feasibility of enhancing the growth performance of submerged salmonids through photoperiod manipulation.
The Potential of Plant Tissue Cultures to Improve the Steviol Glycoside Profile of Stevia (Stevia rebaudiana Bertoni) Regenerants
Authors: Dyduch-Siemińska Magdalena , Wawerska Karolina , Gawroński Jacek
Published: December 2024

The use of in vitro cultures in plant breeding allows for obtaining cultivars with improved properties. In the case of Stevia rebaudiana Bert., genotypes with an appropriate rebaudioside A/stevioside ratio are desirable. The use of indirect organogenesis allows for the induction of somaclonal variation, which, consequently, results in obtaining variability within the regenerants. The Murashige and Skoog medium containing 4.0 mg × dm−3 6-benzylaminopurine (BAP), 2.0 mg × dm−3 1-naphthaleneacetic acid (NAA), and 2.0 mg × dm−3 2,4-dichlorophenoxyacetic acid (2,4-D) resulted in obtaining plants that were biochemically and genetically diverse. The obtained regenerants were characterized by an increased content of rebaudioside A and a better rebaudioside A/stevioside ratio. Genetic analysis using SCoT (start-codon-targeted) markers showed their diversity at the molecular level. Moreover, this study showed that genotype multiplication through six subsequent re-cultures does not cause variability at the genotype level and does not affect the steviol glycoside profile. This study is the first report on obtaining genotypes with higher rebaudioside A content and a more attractive rebaudioside A to stevioside ratio through the use of in vitro cultures. The improved regenerants can be used as parents in hybridization programs or directly as valuable new genotypes.
Oat Beta-Glucans Modulate the Gut Microbiome, Barrier Function, and Immune Responses in an In Vivo Model of Early-Stage Colorectal Cancer
Authors: Guzowska Magdalena , Dziendzikowska Katarzyna , Kopiasz Łukasz , Gajewska Małgorzata , Wilczak Jacek , Harasym Joanna , Czerwińska Malwina , Gromadzka-Ostrowska Joanna
Published: December 2024

Oat beta-glucans (OBGs) are known for their beneficial effects on gut health, including anti-inflammatory and prebiotic effects. The aim of this study was to evaluate the impact of two doses (1% or 3% w/w) of dietary low-molar-mass OBG supplementation on colorectal cancer (CRC) development, immune cell profiles, intestinal barrier protein expression, and microbiota composition in a rat model of CRC induced by azoxymethane (AOM). Microbiome analysis revealed significant differences between the control and CRC groups. OBG supplementation influenced microbial diversity and abundance, particularly increasing the population of beneficial bacteria, such as Lachnospiraceae and Ruminococcaceae, associated with butyrate production. However, higher doses of OBG (3%) led to a decrease in butyrate-producing bacteria and a shift toward higher levels of Akkermansia muciniphila and Enterococcus faecalis. Immune cell profiling showed a higher percentage of T lymphocytes (CD3+) in rats fed a diet supplemented with 3% OBG, both in the intraepithelial (IEL) and lamina propria lymphocytes (LPLs). Immunohistochemical analysis of the large intestine revealed a significantly elevated expression of intestinal barrier proteins, i.e., claudin 3 and 4 in rats receiving 1% OBG, while claudin 7 expression was reduced in early-stage CRC. Gene expression analysis also revealed a significant downregulation of Cldn1 in CRC rats. These findings suggest that dietary OBG supplementation modulates the gut microbiota, immune response, and intestinal barrier integrity, with potential implications for nutritional CRC development prevention and treatment strategies.
Immune Microenvironment and the Effect of Vascular Endothelial Growth Factor Inhibition in Hepatocellular Carcinoma
Authors: Oura Kyoko , Morishita Asahiro , Tadokoro Tomoko , Fujita Koji , Tani Joji , Kobara Hideki
Published: December 2024

Systemic therapy for unresectable hepatocellular carcinoma (HCC) has progressed with the development of multiple kinases, such as vascular endothelial growth factor (VEGF) signaling, targeting cancer growth and angiogenesis. Additionally, the efficacy of sorafenib, regorafenib, lenvatinib, ramucirumab, and cabozantinib has been demonstrated in various clinical trials, and they are now widely used in clinical practice. Furthermore, the development of effective immune checkpoint inhibitors has progressed in systemic therapy for unresectable HCC, and atezolizumab + bevacizumab (atezo/bev) therapy and durvalumab + tremelimumab therapy are now recommended as first-line treatment. Atezo/bev therapy, which combines an anti-programmed cell death 1 ligand 1 antibody with an anti-VEGF antibody, is the first cancer immunotherapy to demonstrate efficacy against unresectable HCC. With the increasing popularity of these treatments, VEGF inhibition is attracting attention from the perspective of its anti-angiogenic effects and impact on the cancer-immune cycle. In this review, we outline the role of VEGF in the tumor immune microenvironment and cancer immune cycle in HCC and outline the potential immune regulatory mechanisms of VEGF. Furthermore, we consider the potential significance of the dual inhibition of angiogenesis and immune-related molecules by VEGF, and ultimately aim to clarify the latest treatment strategies that maximizes efficacy.
Temperature-Dependent Cytokine Neutralization Induced by Magnetoelectric Nanoparticles: An In Silico Study
Authors: Marrella Alessandra , Giannoni Paolo , Lenzuni Martina , Suarato Giulia , Fiocchi Serena , Chiaramello Emma , Ravazzani Paolo
Published: December 2024

Inflammatory cytokines cooperate to maintain normal immune homeostasis, performing both a protective and a pro-inflammatory action in different body districts. However, their excessive persistence or deregulated expression may degenerate into tissue chronic inflammatory status. Advanced therapies should be designed to deploy selective cytokine neutralizers in the affected tissues. Magnetoelectric nanoparticles (MENPs) possess unexploited potentialities, conjugating their ferromagnetic nature, which enables confinement in a specific tissue by directed positioning when subjected to low-intensity magnetic fields, with the capability to generate high electric fields with elevated spatial resolution when subjected to higher magnetic fields. This work proposes to exploit the extremely localized heat generated by Joule’s effect around MENPs under an external magnetic field to denature a harmful cytokine in a hypothetical tissue site. An interdisciplinary and multiphysics in silico study was conducted to provide comprehensive modeling of the temperature distribution generated by MENPs decorated with a membrane-derived microvesicle (MV) coating designed to allocate a specific antibody to bind a target cytokine. A damage model was also implemented to provide an estimation of the influence of several design parameters on the cytokine denaturation efficacy, with the final goal of guiding the future development of effective MENPs-based therapeutic applications and strategies.
Genome-Wide Identification and Analysis of BrTCP Transcription Factor Family Genes Involved in Cold Stress Tolerance in Winter Rapeseed (Brassica rapa L.)
Authors: Xu Yanxia , Ma Li , Zeng Xiucun , Xu Yaozhao , Tao Xiaolei , Fahim Abbas Muhammad , Liu Lijun , Wu Junyan , Yang Gang , Pu Yuanyuan , Fan Tingting , Wang Wangtian , Sun Wancang
Published: December 2024

TCP transcription factors are important during plant growth and stress responses. However, their role in the cold stress response of Brassica rapa L. remains poorly understood. In this research, we identified the TCPs gene family in B. rapa to learn the features of the BrTCP gene family, functionally annotating the interacting proteins of TCP4 and analyzing their expression levels. Our results illustrated the presence of 19 members of the BrTCPs family in B. rapa, exhibiting molecular weights ranging from 27,367.45 to 59,433.64 Da. All identified proteins were classified as unstable, with isoelectric points ranging from 5.5 to 9.48. Subcellular localization forecasted that TCP proteins were all positioned in the nucleus. The BrTCP gene structure is relatively simple, with only seven members possessing introns, and none of the members contain UTR regions. BrTCPs comprise hormone-, light-, and stress-responsive elements. We found that the frequency of photoresponsive elements was greatest in the promoter region, suggesting that BrTCP genes are regulated by light signals and function synergistically with plant growth and development. In addition, five candidate interaction proteins of BrTCP4 were identified using yeast two-hybrid screening. RNA-Seq and q-PCR analyses of the interacting genes revealed differential expression of BrTCP family genes across various tissues following cold stress. Significant responses were observed under low-temperature stress, drought stress, and rehydration treatment, suggesting that these genes play crucial roles as regulators of the molecular network mechanisms responding to stress. This study enhances our understanding of the BrTCP family and provides significant insights into the stress tolerance mechanisms of B. rapa.
Genomic Variability Survey in Ilex aquifolium L., with Reference to Four Insular Populations from Eastern Europe
Authors: Mihali Ciprian Valentin , Mizeranschi Alexandru Eugeniu , Ilie Daniela Elena , Cziszter Ludovic-Toma , Neamț Radu Ionel , Anton Andreea Ștefania , Mathe Endre , Pecsenye Bence , Bota Viviane Beatrice , Turcuș Violeta
Published: December 2024

Cosmopolitan in the western areas of Europe as well as on other continents, the Ilex genus is interesting for its genetic, phenotypic, and biogeographic variabilities. Its insular/local distribution, according to existing data on the periphery of the central and southern European areas, represents a suitable case study with reference to the adaptive plasticity or acclimatization of the Ilex aquifolium L. species to new climatic conditions. The aim of the present study was to analyze the genetic variability at the genome level in four insular populations of Ilex aquifolium L., i.e., in three spontaneous populations from Romania (RO), Serbia (SR), and Bulgaria (BG) and a cultivated population from Hungary (HU). According to the obtained results, the most genetically similar populations among the four considered in this study were those from SR and RO. Genetic variation overlapped genes that were generally associated with metabolic regulation/transport factors, water, and abiotic stress factors. The analysis of single-nucleotide polymorphisms (SNPs) at the levels of the chloroplast and mitochondrion, from the point of view of their distributions at the gene level, identified two clusters: one that includes the native populations (BG, SR, and RO) and a second one including the cultured population from HU.
Visualized Nucleic Acid Hybridization Lateral Flow Strip Integrating with Microneedle for the Point-of-Care Authentication of Ophiocordyceps sinensis
Authors: Liu Haibin , Wang Xinyue , Tian Hang , Yuan Yi , Wang Jing , Cheng Yani , Sun Linyao , Chen Hongshuo , Song Xiaoming
Published: December 2024

Due to the price and demand of Ophiocordyceps sinensis having increased dramatically, adulteration with other fungi is a common problem. Thus, a reliable method of authentic O. sinensis identification is essential. In the present work, a rapid DNA extraction and double-tailed recombinase polymerase amplification (RPA) coupled with nucleic acid hybridization lateral flow strip (NAH-LFS) was developed to distinguish authentic O. sinensis ingredients from other fungi substitutes. In the presence of O. sinensis, the RPA amplicons with two ssDNA tails in the opposite ends, which could simultaneously bind with the SH-probes on gold nanoparticles (AuNPs) and capture the probe on the test line, formed visible red bands. RPA combined with NAH-LFS can efficiently detect O. sinensis DNA down to 1.4 ng/μL; meanwhile, the specificity test validated no cross reaction with common adulterants, including Cordyceps gunnii, Cordyceps cicadae, Cordyceps militaris, yungui Cordyceps, and Ophiocordyceps nutans. The whole RPA-NAH-LFS could be completed within 16 min. The RPA-NAH-LFS results in detecting 20 commercial O. sinensis samples are consistent with PCR-AGE and RT-PCR, confirming the feasibility of the RPA-NAH-LFS method. In conclusion, these results are expected to facilitate the application of RPA-NAH-LFS in the authentication detection of O. sinensis materials, providing a convenient and efficient method for O. sinensis quality control.
Pitfalls of Using ANS Dye Under Molecular Crowding Conditions
Authors: Silonov Sergey A. , Kuklin Alexander I. , Nesterov Semen V. , Kuznetsova Irina M. , Turoverov Konstantin K. , Fonin Alexander V.
Published: December 2024

The 1-anilino-8-naphthalenesulfonate (ANS) fluorescent dye is widely used in protein folding studies due to the significant increase in its fluorescence quantum yield upon binding to protein hydrophobic regions that become accessible during protein unfolding. However, when modeling cellular macromolecular crowding conditions in protein folding experiments in vitro using crowding agents with guanidine hydrochloride (GdnHCl) as the denaturant, the observed changes in ANS spectral characteristics require careful consideration. This study demonstrates that crowding agents can form clusters that interact differently with ANS. Furthermore, GdnHCl can disrupt these clusters and directly affect the ANS spectral characteristics. A model for the interaction between GdnHCl, crowders, and ANS is proposed. Using bovine serum albumin (BSA) as a model protein, the limitations of using ANS for studying conformational transitions induced by GdnHCl in the presence of crowding agents are demonstrated.
Micellar Choline-Acetyltransferase Complexes Exhibit Ultra-Boosted Catalytic Rate for Acetylcholine Synthesis—Mechanistic Insights for Development of Acetylcholine-Enhancing Micellar Nanotherapeutics
Authors: Dante Davide , Jangra Jatin , Baidya Anurag T. K. , Kumar Rajnish , Darreh-Shori Taher
Published: December 2024

Choline-acetyltransferase (ChAT) is the key cholinergic enzyme responsible for the biosynthesis of acetylcholine (ACh), a crucial signaling molecule with both canonical neurotransmitter function and auto- and paracrine signaling activity in non-neuronal cells, such as lymphocytes and astroglia. Cholinergic dysfunction is linked to both neurodegenerative and inflammatory diseases. In this study, we investigated a serendipitous observation, namely that the catalytic rate of human recombinant ChAT (rhChAT) protein greatly differed in buffered solution in the presence and absence of Triton X-100 (TX100). At a single concentration of 0.05% (v/v), TX100 boosted the specific activity of rhChAT by 4-fold. Dose–response analysis within a TX100 concentration range of 0.8% to 0.008% (accounting for 13.7 mM to 0.013 mM) resulted in an S-shaped response curve, indicative of an over 10-fold boost in the catalytic rate of rhChAT. This dramatic boost was unlikely due to a mere structural stabilization since it remained even after the addition of 1.0 mg/mL gelatin to the ChAT solution as a protein stabilizer. Furthermore, we found that the catalytic function of the ACh-degrading enzyme, AChE, was unaffected by TX100, underscoring the specificity of the effect for ChAT. Examination of the dose–response curve in relation to the critical micelle concentration (CMC) of TX100 revealed that a boost in ChAT activity occurred when the TX100 concentration passed its CMC, indicating that formation of micelle–ChAT complexes was crucial. We challenged this hypothesis by repeating the experiment on Tween 20 (TW20), another non-ionic surfactant with ~3-fold lower CMC compared to TX100 (0.06 vs. 0.2 mM). The analysis confirmed that micelle formation is crucial for ultra-boosting the activity of ChAT. In silico molecular dynamic simulation supported the notion of ChAT–micelle complex formation. We hypothesize that TX100 or TW20 micelles, by mimicking cell–membrane microenvironments, facilitate ChAT in accessing its full catalytic potential by fine-tuning its structural stabilization and/or enhancing its substrate accessibility. These insights are expected to facilitate research toward the development of new cholinergic-enhancing therapeutics through the formulation of micelle-embedded ChAT nanoparticles.
Early Mortality Prediction in Intensive Care Unit Patients Based on Serum Metabolomic Fingerprint
Authors: Araújo Rúben , Ramalhete Luís , Von Rekowski Cristiana P. , Fonseca Tiago A. H. , Bento Luís , R. C. Calado Cecília
Published: December 2024

Predicting mortality in intensive care units (ICUs) is essential for timely interventions and efficient resource use, especially during pandemics like COVID-19, where high mortality persisted even after the state of emergency ended. Current mortality prediction methods remain limited, especially for critically ill ICU patients, due to their dynamic metabolic changes and heterogeneous pathophysiological processes. This study evaluated how the serum metabolomic fingerprint, acquired through Fourier-Transform Infrared (FTIR) spectroscopy, could support mortality prediction models in COVID-19 ICU patients. A preliminary univariate analysis of serum FTIR spectra revealed significant spectral differences between 21 discharged and 23 deceased patients; however, the most significant spectral bands did not yield high-performing predictive models. By applying a Fast-Correlation-Based Filter (FCBF) for feature selection of the spectra, a set of spectral bands spanning a broader range of molecular functional groups was identified, which enabled Naïve Bayes models with AUCs of 0.79, 0.97, and 0.98 for the first 48 h of ICU admission, seven days prior, and the day of the outcome, respectively, which are, in turn, defined as either death or discharge from the ICU. These findings suggest FTIR spectroscopy as a rapid, economical, and minimally invasive diagnostic tool, but further validation is needed in larger, more diverse cohorts.
Kidney Programming and Hypertension: Linking Prenatal Development to Adulthood
Authors: Tain You-Lin , Hsu Chien-Ning
Published: December 2024

The complex relationship between kidney disease and hypertension represents a critical area of research, yet less attention has been devoted to exploring how this connection develops early in life. Various environmental factors during pregnancy and lactation can significantly impact kidney development, potentially leading to kidney programming that results in alterations in both structure and function. This early programming can contribute to adverse long-term kidney outcomes, such as hypertension. In the context of kidney programming, the molecular pathways involved in hypertension are intricate and include epigenetic modifications, oxidative stress, impaired nitric oxide pathway, inappropriate renin–angiotensin system (RAS) activation, disrupted nutrient sensing, gut microbiota dysbiosis, and altered sodium transport. This review examines each of these mechanisms and highlights reprogramming interventions proposed in preclinical studies to prevent hypertension related to kidney programming. Given that reprogramming strategies differ considerably from conventional treatments for hypertension in kidney disease, it is essential to shift focus toward understanding the processes of kidney programming and its role in the development of programmed hypertension.
Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches
Authors: Ramirez-Falcon Melody , Suarez-Pajes Eva , Flores Carlos
Published: December 2024

Since their discovery, corticosteroids have been widely used in the treatment of several diseases, including asthma, acute lymphoblastic leukemia, chronic obstructive pulmonary disease, and many other conditions. However, it has been noted that some patients develop undesired side effects or even fail to respond to treatment. The reasons behind this have not yet been fully elucidated. This poses a significant challenge to effective treatment that needs to be addressed urgently. Recent genomic, transcriptomic, and other omics-based approximations have begun to shed light into the genetic factors influencing interindividual variability in corticosteroid efficacy and its side effects. Here, we comprehensively revise the recent literature on corticosteroid response in various critical and chronic diseases, with a focus on omics approaches, and highlight existing knowledge gaps where further investigation is urgently needed.
Longitudinal Study of SARS-CoV-2 Vaccinations and Infections in Patients with Gastrointestinal Cancer: Stabilizing Immune Responses and Neutralizing Emerging Variants with Variant-Adapted Antigen Exposures
Authors: Gonzalez-Carmona Maria A. , Schmitz Alina M. , Berger Moritz , Baier Leona I. , Gorny Jens G. , Sadeghlar Farsaneh , Anhalt Thomas , Zhou Xin , Zhou Taotao , Mahn Robert , Möhring Christian , Linnemann Thomas , Schmid Matthias , Strassburg Christian P. , Boesecke Christoph , Rockstroh Jürgen K. , Eis-Hübinger Anna-Maria , Monin Malte B.
Published: December 2024

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer (n = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures. In the pre-Omicron era, humoral SARS-CoV-2 immunity decreased after three antigen contacts without further antigen exposure. While Omicron neutralization was significantly lower than wildtype neutralization (p < 0.01), Omicron infections were yet mild to moderate. Additional Omicron exposures improved IgG levels (p < 0.01) and Omicron neutralization (p < 0.01). However, this effect was significantly less intense in patients with active GI cancer, particularly in patients with pancreaticobiliary neoplasms (PBN; p = 0.04), with underlying immunodeficiency (p = 0.05), and/or under conventional chemotherapy (p = 0.05). Pre-Omicron SARS-CoV-2 immunity prevented severe clinical courses of infections with Omicron variants in patients with GI cancer. However, in patients with PBN, with underlying immunodeficiency, and/or under conventional chemotherapy initial contacts with Omicron antigens triggered only reduced immune responses. Thus, subgroups could be identified for whom booster vaccinations are of special clinical significance.
Novel Isoxazole-Based Antifungal Drug Candidates
Authors: Bąchor Urszula , Brożyna Malwina , Junka Adam , Chmielarz Mateusz Ramires , Gorczyca Damian , Mączyński Marcin
Published: December 2024

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs.
The Pulp, Peel, Seed, and Food Products of Persea americana as Sources of Bioactive Phytochemicals with Cardioprotective Properties: A Review
Authors: Olas Beata
Published: December 2024

Botanically speaking, avocado (Persea americana) is a fruit. It consists of a single large seed surrounded by a creamy, smooth-textured edible mesocarp or pulp covered by a thick, bumpy skin. Avocado is a nutrient-dense fruit, containing a range of bioactive compounds which have been independently associated with cardiovascular health. These compounds have been obtained from the pulp, peel, and seed. This narrative review summarizes the current understanding of the cardioprotective potential of avocado fruit, especially the pulp and seed, and its food products, and examines the biological mechanism behind it.
Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling
Authors: Yang Bo , Yang Kunhuan , Xi Ruitong , Chen Jingmeng , Wu Yalin
Published: December 2024

All-trans-retinal (atRAL)-induced photoreceptor atrophy and retinal degeneration are hallmark features of dry age-related macular degeneration (AMD) and Stargardt disease type 1 (STGD1). The toxicity of atRAL is closely related to the generation of reactive oxygen species (ROS). Quercetin, a natural product, is known for its potent antioxidant properties; however, its effects in mitigating atRAL-mediated retinal damage remains unclear. This study investigated the protective effects of quercetin against atRAL-induced photoreceptor damage. Using atRAL-loaded 661W photoreceptor cells, we evaluated cell viability, ROS generation, and endoplasmic reticulum (ER) stress under quercetin treatment. Quercetin significantly restored the cell viability (to 70%) and reduced ROS generation in atRAL-treated 661W cells. Additionally, Western blot analysis demonstrated that quercetin mitigated protein kinase RNA-like ER kinase (PERK) signaling, preventing ER stress-induced apoptosis. Importantly, in Abca4−/−Rdh8−/− mice, an animal model of light-induced atRAL accumulation in the retina, quercetin treatment effectively alleviated light-exposed photoreceptor atrophy and retinal degeneration by attenuating PERK signaling. Thus, quercetin protected photoreceptor cells from atRAL-induced damage by inhibiting ROS generation and PERK signaling, which suggests its potential as a therapeutic agent for atRAL-related retinal degeneration.
Coordinated Actions of Neurogenesis and Gliogenesis in Nerve Injury Repair and Neuroregeneration
Authors: Chen Mei-Yu , Chi Cheng-Yu , Zheng Chiau-Wei , Wang Chen-Hung , Chiu Ing-Ming
Published: December 2024

The failure of endogenous repair mechanisms is a key characteristic of neurological diseases, leading to the inability to restore damaged nerves and resulting in functional impairments. Since the endogenously regenerative capacity of damaged nerves is limited, the enhancement of regenerative potential of quiescent neural stem cells (NSCs) presents as a therapeutic option for neural diseases. Our previous studies have shown exciting progress in treating sciatic nerve injury in mice and rats using NSCs in conjunction with neurotrophic factors such as fibroblast growth factor 1 (FGF1). Additionally, a recently discovered neurotrophic factor, IL12p80, has shown significant therapeutic effects in sciatic nerve injury repair via myelinating oligodendrocytes. IL12p80 induces oligodendrocyte differentiation from NSCs through phosphorylation of Stat3. Therefore, it might be possible to alleviate the myelination defects of oligodendrocytes in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and even schizophrenia through the administration of IL12p80. These applications could shed light on IL12p80 and FGF1, not only in damaged nerve repair, but also in rectifying the oligodendrocytes’ defects in neurodegenerative diseases, such as ALS and MS. Finally, the synergistic effects of neurogenesis-induced FGF1 and myelination-induced IL12 might be able to supplant the need of NSCs for nerve repair and neuroregeneration.
A Study of Futures Price Forecasting with a Focus on the Role of Different Economic Markets
Authors: Wang Yongxiang , Liu Qingyang , Hu Yanrong , Liu Hongjiu
Published: December 2024

Current research on futures price prediction focuses on the autocorrelation of historical prices, yet the resulting predictions often suffer from issues of inaccuracy and lag. This paper uses Chinese corn futures as the subject of study. First, we identify key influencing factors, such as Chinese soybean futures, U.S. soybean futures, and the U.S.-China exchange rate, that exhibit ‘predictive causality’ with corn futures prices through the Granger causality test. We then apply the sample convolution and interaction network (SCINet) to perform both single-step and multi-step predictions of futures prices. The experimental results show that incorporating key influencing factors significantly improves prediction accuracy. For instance, in the single-step prediction, combining historical prices with Chinese soybean futures prices reduces the MAE and RMSE values by 5.12% and 3.45%, respectively, compared to using historical prices alone. Furthermore, the SCINet model outperforms traditional models such as temporal convolutional networks (TCN), gated recurrent units (GRU), and long short-term memory (LSTM) networks when based solely on historical prices. This study validates the effectiveness of key influencing factors in forecasting Chinese corn futures prices and demonstrates the advantages of the SCINet model in futures price prediction. The findings provide valuable insights for optimising the agricultural futures market and enhancing the ability to predict price risks.
Prospects for Implementation of Autonomous Vehicles and Associated Infrastructure in Developing Countries
Authors: Kurse Teshome Kumsa , Gebresenbet Girma , Daba Geleta Fikadu
Published: December 2024

This study explores the implementation and impact of autonomous vehicle (AV) systems, particularly in developing countries. While AVs promise enhanced road safety by reducing crashes, injuries, and fatalities, their adoption faces significant challenges, including public acceptance and infrastructure readiness. A mixed methods approach was employed, combining quantitative data from surveys of approximately 1500 randomly selected individuals and qualitative insights from in-depth interviews with policymakers, traffic engineers, and industry representatives. The quantitative analysis revealed high levels of perceived usefulness (78.8%), positive attitudes (87.78%), and expected benefits (86.09%) among respondents, indicating optimism about AVs’ potential to improve traffic efficiency and safety. However, concerns about technical reliability, cybersecurity, and the cost of infrastructure upgrades persist. Comparative analysis of physical and digital infrastructure highlighted significant gaps, particularly in road quality, markings, and internet connectivity. Policy implications emphasize the need for targeted public education to build trust and address safety concerns, regulatory reforms to ensure cybersecurity and ethical compliance, and strategic investments in infrastructure to meet AV requirements. Drawing on lessons from international contexts, the study recommends proactive stakeholder engagement and community outreach to align technological advancements with societal needs. These findings provide a roadmap for policymakers to navigate the challenges of AV adoption in Ethiopia and similar contexts, ensuring the integration of automation into sustainable and efficient transportation systems.
Compliance Behaviour After a Coronary Ischaemic Event: A Quasi-Experimental Study of Adherence to a Protocolised Follow-Up in Primary Care
Authors: Lizcano-Álvarez Ángel , Carretero-Julián Laura , Talavera-Sáez Ana , Alameda-Cuesta Almudena , Rodríguez-Vázquez Rocío , Cristobal-Zárate Beatriz , Cid-Expósito María-Gema
Published: December 2024

Following a coronary ischaemic event, it is essential to promote empowerment in self-care decision making. Primary care nursing is crucial for intensive follow-up to promote adherence to the therapeutic regimen. Objective: To ascertain whether adherence to a protocolised follow-up programme, with the support of a patient notebook, improves compliance behaviours in terms of physical activity, prescribed diet and medication. This is a quasi-experimental multicentre pre/post study. Population: Individuals aged 40–70 years, diagnosed with cardiac ischaemia in the last 18 months with a follow-up from March 2017 to January 2019, were included in a protocolised follow-up programme consisting of 11 visits over 12 months. A total of 194 patients started the programme and 132 completed it. Of these, 67.4% exhibited good adherence to follow-up, 31.8% exhibited medium adherence, and 0.8% exhibited poor adherence. Therefore, the patients were recoded into two variables: Medium–Low Adherence and High. The Nursing Outcomes Classification variables were significantly different between the Poor–Medium and Good Adherence groups and were always higher in the Good Adherence group (p-values < 0.05 t-student). There was a significant relationship between level of adherence and compliance behaviour. Good adherence to a follow-up plan led by primary care nurses improves compliance behaviours in terms of prescribed diet, physical activity, and medication. Early, intensive and protocolised follow-up by primary care nurses is essential to improve adherence to the therapeutic regimen and compliance behaviour among individuals with cardiac ischaemia. The use of a cardiovascular self-care notebook promotes adherence.