bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Bioavailability Assessment of an Estriol-Containing Vaginal Hydrogel
Authors: Takacs Peter , Kozma Barbara , Rátonyi Dávid , Kozma Bence , Attila Kiss-Szikszai , Fenyvesi Ferenc , Sipos Attila G.
Published: December 2024

Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy.
Exploring the Molecular Link Between Diabetes and Erectile Dysfunction Through Single-Cell Transcriptome Analysis
Authors: Begum Mahmuda , Choubey Mayank , Tirumalasetty Munichandra Babu , Arbee Shahida , Sadik Sibly , Mohib Mohammad Mohabbulla , Srivastava Shivani , Minhaz Naofel , Alam Riffat , Mohiuddin Mohammad Sarif
Published: December 2024

Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35–75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility.
The Birth of the “Indian” Clinic: Daktari Medicine in A Ballad of Remittent Fever
Authors: Gurunathan Thiyagaraj , Mishra Binod
Published: December 2024

This article locates the clinic as a historically contingent space which faced cultural resistance and remained alien to the colonized population in India. It corroborates the socio-political tension in setting up a clinic within the colony and investigates how the Western clinic as a colonial apparatus was resituated as the “Indian clinic” per se. With the historical emergence of a new class of medical practitioners called “daktars” (a Bengali vernacularization of the term “doctor”), the health-seeking behaviour and public health model of colonial India witnessed a decolonial shift. Unlike their English counterparts, daktars did not enjoy a privileged position within the medical archives of colonial India. This archival gap within Indian medical history presents itself as a viable topic for discussion through the means of the literature of the colonized. Bengali writer Ashoke Mukhopadhyay’s novel Abiram Jwarer Roopkotha (2018), translated into English as A Ballad of Remittent Fever in 2020, remedies the colonial politics of the archive by reconstructing the lives of various daktars and their pursuit of self-reliance. The article takes a neo-historical approach towards understanding and assessing the past of daktari medicine and thereby offers comments on its traces in the contemporary public health of India.
Machine Learning-Driven Metabolic Syndrome Prediction: An International Cohort Validation Study
Authors: Li Zhao , Wu Wenzhong , Kang Hyunsik
Published: December 2024

Background/Objectives: This study aimed to develop and validate a machine learning (ML)-based metabolic syndrome (MetS) risk prediction model. Methods: We examined data from 6155 participants of the China Health and Retirement Longitudinal Study (CHARLS) in 2011. The LASSO regression feature selection identified the best MetS predictors. Nine ML-based algorithms were adopted to build predictive models. The model performance was validated using cohort data from the Korea National Health and Nutrition Examination Survey (KNHANES) (n = 5297), the United Kingdom (UK) Biobank (n = 218,781), and the National Health and Nutrition Examination Survey (NHANES) (n = 2549). Results: The multilayer perceptron (MLP)-based model performed best in the CHARLS cohort (AUC = 0.8908; PRAUC = 0.8073), the logistic model in the KNHANES cohort (AUC = 0.9101, PRAUC = 0.8116), the xgboost model in the UK Biobank cohort (AUC = 0.8556, PRAUC = 0.6246), and the MLP model in the NHANES cohort (AUC = 0.9055, PRAUC = 0.8264). Conclusions: Our MLP-based model has the potential to serve as a clinical application for detecting MetS in different populations.
Venetoclax Plus Intensified Chemoimmunotherapy as a Bridge to Allogeneic Stem Cell Transplantation in Richter Syndrome: Report of Two Cases
Authors: Derenzini Enrico , Cignetti Alessandro , Tabanelli Valentina , Gottardi Daniela , Gerbino Elvira , Vanazzi Anna , Sammassimo Simona , Maraglino Alessio Maria Edoardo , Melle Federica , Motta Giovanna , Malengo Daniela , Omodeo Salè Emanuela , Bonello Lisa , Pastano Rocco , Pileri Stefano , Carnevale Schianca Fabrizio , Tarella Corrado
Published: December 2024

Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.
Examining Teachers College Student Perceptions of Their Personal Wellness During the COVID-19 Pandemic
Authors: Farrand Kathleen M. , Rodriguez-Martinez Sara
Published: December 2024

The purpose of this paper is to examine how college students perceived their personal wellness and identified their sources of support while enrolled as a college student in a teacher’s college during the COVID-19 pandemic. College education students were asked to provide responses for five different wellness measures. Quantitative data analysis was used to examine overall wellness, well-being, self-efficacy, food insecurity, and sources of support. Females had significantly lower wellness scores than males. Undergraduates had noticeably lower wellness scores than graduate students, and undergraduates had significantly higher Food Insecurity scores than graduate students did. Professors and administrators were scored significantly above average as a source of support for college students, whereas Campus Medical Service and Campus Mental Health scored as below average as a source of support. Utilizing wellness data about a variety of factors can help college mental health professionals implement specific sources of support to address mental health for college students.
Discrimination of Farming Practices Through Olive Leaf Phenolic and Mineral Analysis
Authors: Franić Mario , Pasković Igor , Marcelić Šime , Lukić Igor , Major Nikola , Palčić Igor , Goreta Ban Smiljana , Polić Pasković Marija
Published: December 2024

The content and composition of phenolic compounds and mineral elements in olive leaves are susceptible to variation influenced by various factors, such as genotype, environment, and agricultural practices. The aim of this study was to investigate and compare the response of phenolics and minerals to organic and integrated farming systems. Trees from three olive cultivars grown in two neighboring olive groves with different farming systems were used. After sampling during pruning in two consecutives sampling years, the contents of phenolics and minerals in olive leaves was determined by high-performance liquid chromatography (HPLC) and inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis, respectively. The obtained results revealed a complex response of both phenolics and minerals, strongly influenced by interactions among the factors, such as farming system, cultivar, and sampling year. Specific phenolic compounds, such as luteolin-4-O-glucoside and luteolin-7-O-glucoside, were particularly abundant under organic farming conditions. Others, like oleuropein and oleacein, followed a similar trend, though they were more strongly affected by different cultivar and sampling year combinations. A lower content of mineral elements was generally observed under organic farming conditions, although it was also significantly affected by cultivar and sampling year. The results of this study have the potential to be utilized for the enhanced production of organic olive leaves as a reliable source of valuable phytochemicals for nutraceuticals, functional foods, and dietary supplements.
In Vitro Morpho-Anatomical and Regeneration Features of Cultivars of Actinidia kolomikta (Maxim.) Maxim
Authors: Krakhmaleva Irina Leonidovna , Molkanova Olga Ivanovna , Orlova Natalia Dmitrievna , Koroleva Olga Vasilevna , Mitrofanova Irina Vjacheslavovna
Published: December 2024

Actinidia kolomikta (Maxim) Maxim. is a winter-hardy species of the genus Actinidia Lindl., whose fruits are valued for their high content of vitamin C and other bioactive compounds. The use of biotechnological propagation methods significantly accelerates the production of quality planting materials for this crop. This study revealed the regeneration features of promising A. kolomikta cultivars. The main morphometric parameters of explants were determined in regard to the effect of different iron chelates (FeEDTA and FeEDDHA) and cytokinins (6-benzylaminopurine, meta-Topolin, and 2-izopentyladenine) in the Quoirin and Lepoivre medium. FeEDTA-supplemented media were optimal for explant culture. Meta-Topolin was found to promote the formation of adventitious microshoots at the base of explants and bud activation, which increased the multiplication rate by 1.5 and 1.7 times compared to the media with 6-benzylaminopurine and 2-izopentyladenine. The morpho-anatomical studies revealed the structural organization of assimilation tissues and the stomatal apparatus of A. kolomikta under different culture conditions (field, in vitro, and ex vitro). The stomata in vitro were round and had a larger area, lower thickness, and a lower layer number of mesophyll compared to field conditions. The transfer from in vitro to ex vitro caused gradual normalization of the leaf structure: a decrease in the stomatal number and area, changes in shape (from round to elliptical), and an increase in the mesophyll thickness.
Exogenous Sucrose Enhances Growth and Physiological Performance of Tomato Seedlings Under Suboptimal Light Conditions in Passive Greenhouses
Authors: Gómez-Cabezas Miguel , España Ángelo
Published: December 2024

Tomato is an important crop worldwide. Commonly, the production process is initiated in nurseries that provide seedlings to greenhouse growers. Many factors influence crop production, one of which is the seedlings’ quality. Light has an enormous effect on seedlings; however, in passive greenhouses, its control is quite difficult. In this situation, plants are usually affected by low or high light intensities which induces poor growth on plants. On the other hand, there is some evidence that sucrose applications could compensate for the adverse effects caused by low light intensities and other abiotic factors like salinity, drought, and temperature. In this way, this research aimed to assess the impact of exogenous sucrose on the morphology, quality, and growth of tomato seedlings cultivated under low-tech greenhouse conditions commonly observed in tropical and subtropical commercial nurseries. Four sucrose treatments were proposed (0, 1, 10, and 100 mM). On days 28, 32, 36, 40, and 44 after sowing, several morphological, physiological and growth measurements were evaluated. Sucrose-treated plants displayed higher leaf areas and chlorophyll contents, facilitating light absorption. Therefore, the relative growth rate (RGR) was enhanced and better explained by a higher net assimilation rate (NAR). Consequently, a higher dry matter accumulation and Dixon quality index (DQI) were achieved. Plants under treatment at 100 mM exhibited the best performance.
Adherence to Pulmonary Tuberculosis Medication and Associated Factors Among Adults: A Cross-Sectional Study in the Metinaro and Becora Sub-Districts, Dili, Timor-Leste
Authors: Fernandes Amentinho , Laohaprapanon Sawanya , Nam Truong Thanh , Sequeira Ercia Maria Da Conceicao , Le Cua Ngoc
Published: December 2024

Timor Leste is one of the top countries in Asia with a high incidence rate of pulmonary tuberculosis (TB). The success of TB treatment necessitated a more profound comprehension of adherence as a multifaceted behavioral issue, along with identifying the barriers that hinder and the factors that promote patient adherence. This study aimed to assess the rate of pulmonary TB medication adherence and identify its predictors among adults in Metinaro and Becora, Dili, Timor-Leste. A descriptive analytical cross-sectional study was conducted, and new patients with pulmonary TB aged 18 years and above were selected using a proportional sampling method. Quantitative data were collected from 398 patients with pulmonary tuberculosis. The medication adherence results were as follows: 73.6% low adherence, 18.3% moderate adherence, and only 8.1% high adherence. The study identified significant predictors of medication adherence, such as health service factors (OR = 14.024, 95% CI: 5.42–35.54, p = 0.001). Patients who perceived a high quality in the health service were 14 times more likely to exhibit higher medication adherence. Regarding individual behaviors, patients who consumed alcohol or occasionally engaged in physical exercise were significantly less likely to exhibit higher medication adherence (OR = 0.17, 95% CI: 0.091–0.312, p = 0.001). Similarly, patients experiencing high levels of stigma were less likely to achieve strong adherence (OR = 0.146, 95% CI: 0.058–0.326, p = 0.001).Both health service quality and individual factors, such as lifestyle behaviors and social stigma, were statistically significant predictors ofTB medication adherence. Enhancing the healthcare infrastructure, implementing multisectoral strategies for behavior change, and reducing stigma are crucial. Additionally, mobile health technologies, like SMS reminders and telehealth, might support real-time adherence improvements.
Early Family Conflict and Behavioral Outcomes in Children from Low-Income Families: The Indirect Effects of Parental Depression and Parenting Practices
Authors: Huang Rong , Chazan-Cohen Rachel , Carlson Delaina
Published: December 2024

Family conflict has been demonstrated as a risk factor impacting children’s mental health and behaviors; however, the mechanisms underlying these connections are unclear. Focusing on 1622 children from low-income families (51.4% boys, 38.3% White, 35.5% Hispanic/Latino, 22.1% African American, 4.1% other), the current study examines the role that maternal depression and parenting behaviors play in the associations between family conflict in early childhood and children’s internalizing and externalizing behaviors in early adolescence. Family conflict was positively associated with maternal depression at age 3 and detached parenting at age 5; however, maternal depression was linked to increased child internalizing and externalizing behaviors, and detached parenting was associated with decreased behavioral outcomes. Maternal depression at age 3 and intrusive parenting at age 5 successively mediated the association between family conflict and child externalizing. Multi-group analysis indicated different indirect paths of parenting behaviors in boys and girls. Specifically, in boys, the indirect effect of detached parenting on the links between family conflict and externalizing and internalizing behaviors was sustained. In girls, maternal depression and intrusive parenting sequentially explained the link between family conflict and externalizing behaviors. The findings highlighted the importance of addressing family well-being and parenting support, especially for children from low-income families.
Genome-Wide Identification, Functional Characterization, and Stress-Responsive Expression Profiling of Subtilase (SBT) Gene Family in Peanut (Arachis hypogaea L.)
Authors: Li Shipeng , Fu Huiwen , Sharif Yasir , Abdullaziz Sheidu , Wang Lihui , Zhang Yongli , Zhuang Yuhui
Published: December 2024

Subtilases (SBTs), known as serine proteases or phytoproteases in plants, are crucial enzymes involved in plant development, growth, and signaling pathways. Despite their recognized importance in other plant species, information regarding their functional roles in cultivated peanut (Arachis hypogea L.) remains sparse. We identified 122 AhSBT genes in the STQ peanut genome, classifying them into six subgroups based on phylogenetic analysis. Detailed structural and motif analyses revealed the presence of conserved domains, highlighting the evolutionary conservation of AhSBTs. The collinearity results indicate that the A. hypogea SBT gene family has 17, 5, and 1 homologous gene pairs with Glycine max, Arabidopsis thaliana, and Zea mays, respectively. Furthermore, the prediction of cis-elements in promoters indicates that they are mainly associated with hormones and abiotic stress. GO and KEGG analyses showed that many AhSBTs are important in stress response. Based on transcriptome datasets, some genes, such as AhSBT2, AhSBT18, AhSBT19, AhSBT60, AhSBT102, AhSBT5, AhSBT111, and AhSBT113, showed remarkably higher expression in diverse tissues/organs, i.e., embryo, root, and leaf, potentially implicating them in seed development. Likewise, only a few genes, including AhSBT1, AhSBT39, AhSBT53, AhSBT92, and AhSBT115, were upregulated under abiotic stress (drought and cold) and phytohormone (ethylene, abscisic acid, paclobutrazol, brassinolide, and salicylic acid) treatments. Upon inoculation with Ralstonia solanacearum, the expression levels of AhSBT39, AhSBT50, AhSBT92, and AhSBT115 were upregulated in disease-resistant and downregulated in disease-susceptible varieties. qRT-PCR-based expression profiling presented the parallel expression trends as generated from transcriptome datasets. The comprehensive dataset generated in the study provides valuable insights into understanding the functional roles of AhSBTs, paving the way for potential applications in crop improvement. These findings deepen our understanding of peanut molecular biology and offer new strategies for enhancing stress tolerance and other agronomically important traits.
Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids
Authors: Dilloo Silvia , Whittaker Anne , Chang Xinyue , D’Amen Eros , Spisni Enzo , Hrelia Silvana , Angeloni Cristina , Malaguti Marco , Dinelli Giovanni , Truzzi Francesca
Published: December 2024

The anti-cancer potential of eugenol (EUG) is well recognized, whereas that of spermidine (SPD) is subject to dispute and requires further research. The anti-tumorigenic potential of wheat germ SPD (150 µM) and clove EUG (100 µM), alone, in combination as SPD+EUG (50 µM + 100 µM) and, as a supplement (SUPPL; 0.6 µM SPD + 50 µM EUG), was investigated on both metastatic SW620 and primary Caco-2 colorectal cancer (CRC) spheroids. Compared to untreated controls, all treatments significantly reduced the vitality and spheroid area, increased the necrotic area, and induced apoptosis on both cell-type spheroids after 96 h, with a reduced migration evident in 2D (two-dimensional) cultures after 48 h. The comparable anti-CRC effects of the SPD+EUG and the SUPPL reflected a wide-range dose efficacy of SPD and EUG. It is of note that SPD+EUG induced a synergistic effect on the increased caspase-3 expression and reduced the migration percentage in SW620. In more physiologically relevant intestinal equivalents (healthy enterocytes [NCM460], fibroblasts [L929], and monocytes [U937]) containing embedded SW620/Caco-2 spheroids, SPD+EUG administration significantly reduced the spheroid CEA marker and proliferation, whilst simultaneously increasing occludin, autophagy LC3-II expression, and monocyte differentiation, compared to the control models. Exogenous SPD, alone and in combination with EUG, displayed an anti-CRC potential on tumor growth and metastasis, and warrants further investigation.
Advances in Stem Cell Research—Insights from the Special Issue “Stem Cells in Health and Disease 2.0”
Authors: Galow Anne-Marie , Agriesti Francesca
Published: December 2024

Significant progress in stem cell research over the last few decades has opened up new avenues for exploring human physiology and pathophysiology [...]
Molecular Dynamics Simulations Suggest That Side-Chain Motions of Charged Amino Acids Determine Long-Range Effects in Proteins: An Egg of Coulomb
Authors: Niccolai Neri , Morandi Edoardo , Bernini Andrea
Published: December 2024

Living systems cannot rely on random intermolecular approaches toward cell crowding, and hidden mechanisms must be present to favor only those molecular interactions required explicitly by the biological function. Electromagnetic messaging among proteins is proposed from the observation that charged amino acids located on the protein surface are mostly in adjacent sequence positions and/or in spatial proximity. Molecular dynamics (MD) simulations have been used to predict electric charge proximities arising from concerted motions of charged amino acid side chains in two protein model systems, human ubiquitin and the chitinolytic enzyme from Ostrinia furnacalis. This choice has been made for their large difference in size and sociality. Protein electrodynamics seems to emerge as the framework for a deeper understanding of the long-distance interactions of proteins with their molecular environment. Our findings will be valuable in orienting the design of proteins with specific recognition patterns.
The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review
Authors: Zhong Hanyi , Zhou Ziling , Wang Han , Wang Ruo , Shen Kunwei , Huang Renhong , Wang Zheng
Published: December 2024

Epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is a highly invasive and malignant type of tumor. Due to its resistance to HER2-targeted therapy, HER2+ BC has a poor prognosis and a tendency for metastasis. Understanding the mechanisms underlying this resistance and developing effective treatments for HER2+ BC are major research challenges. The phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, which is frequently altered in cancers, plays a critical role in cellular proliferation and drug resistance. This signaling pathway activates various downstream pathways and exhibits complex interactions with other signaling networks. Given the significance of the PI3K/AKT pathway in HER2+ BC, several targeted drugs are currently in development. Multiple drugs have entered clinical trials or gained market approval, bringing new hope for HER2+ BC therapy. However, new drugs and therapies raise concerns related to safety, regulation, and ethics. Populations of different races and disease statuses exhibit varying responses to treatments. Therefore, in this review, we summarize current knowledge on the alteration and biological roles of the PI3K/AKT pathway, as well as its clinical applications and perspectives, providing new insights for advancing targeted therapies in HER2+ BC.
Comparative Transcriptomic Analysis and Candidate Gene Identification for Wild Rice (GZW) and Cultivated Rice (R998) Under Low-Temperature Stress
Authors: Yu Yongmei , Liu Dilin , Wang Feng , Kong Le , Lin Yanhui , Chen Leiqing , Jiang Wenjing , Hou Xueru , Xiao Yanxia , Fu Gongzhen , Liu Wuge , Huo Xing
Published: December 2024

Rice is a short-day thermophilic crop that originated from the low latitudes of the tropics and subtropics; it requires high temperatures for growth but is sensitive to low temperatures. Therefore, it is highly important to explore and analyze the molecular mechanism of cold tolerance in rice to expand rice planting areas. Here, we report a phenotypic evaluation based on low-temperature stress in indica rice (R998) and wild rice (GZW) and a comparative transcriptomic study conducted at six time points. After 7 days of low-temperature treatment at 10 °C, R998 exhibited obvious yellowing and greening of the leaves, while GZW exhibited high low-temperature resistance, and the leaves maintained their normal morphology and exhibited no yellowing; GZW has a higher survival rate. Principal component analysis (PCA) and cluster analysis of the RNA-seq data revealed that the difference in low-temperature resistance between the two cultivars was caused mainly by the difference in low-temperature treatment after 6 h. Differential expression analysis revealed 2615 unique differentially expressed genes (DEGs) in the R998 material, 1578 unique DEGs in the GZW material, 1874 unique DEGs between R998 and GZW, and 2699 DEGs that were differentially expressed not only between cultivars but also at different time points in the same material under low-temperature treatment. A total of 15,712 DEGs were detected and were significantly enriched in the phenylalanine metabolism, photosynthesis, plant hormone signal transduction, and starch and sucrose metabolism pathways. These 15,712 DEGs included 1937 genes encoding transcription factors (TFs), of which 10 have been identified with functional validation in previous studies. In addition, a gene regulatory network was constructed via weighted gene correlation network analysis (WGCNA), and 12 key genes related to low-temperature tolerance in rice were identified, including five genes encoding TFs, one of which was identified and verified in previous studies. These results provide a theoretical basis for an in-depth understanding of the molecular mechanism of low-temperature tolerance in rice and provide new genetic resources for the study of low-temperature tolerance in rice.
Novel Peptidomimetic Cyclo-{E(I)-E(W)}Na (CP-88) with Hematopoietic Activity Sustained in Invasive and Oral Administration: Experimental and Preclinical Evaluation
Authors: Deigin Vladislav , Vinogradova Yulia , Vinogradov Dmitriy , Linkova Natalia , Dyatlova Anastasiia , Medvedev Dmitrii , Krasichkov Alexander , Polyakova Victoria
Published: December 2024

Over the last decades, significant progress has been made in studying agonistic and antagonistic hematopoietic peptides. The main disadvantage of this class of peptides is their low stability with noninvasive administration methods, which limits the widespread use of hematopoiesis-regulated peptide drugs in medical practice. The aim of this work is to study novel peptidomimetics with hematopoietic activity sustained in invasive and oral administration. The activity of the leading compound cyclopeptide Cyclo—[Glu(Ile)-Glu(Trp)] (CP-88) was compared to that of the pharmaceutical preparation Stemokin in stimulating the population of committed colony-forming cells in intact and irradiated mice. CP-88 peptide increases the relative number of CD34+ cells in the blood and bone marrow, leading to expanded hematopoietic stem cells. CP-88 peptide, applied 48 h before bone marrow extraction, stimulates the population of committed colony-forming cells in the normal bone marrow by 33–37% above the normal level. In recipient mice injected with irradiated bone marrow, this peptide was restored practically to normal levels of colony-forming cells in a wide range of doses at intraperitoneal and oral administration. The toxicological results conclude that in humans, considering interspecies extrapolation, the CP-88 peptide can be practically safe with a single and course administration in doses of up to 100 μg/kg. The results of this investigation underscore the significant potential of CP-88 peptide as a hematopoiesis-regulated drug and instill optimism for its future application in medical practice.
Inhibiting De Novo Biosynthesis of Ceramide by L-Cycloserine Can Prevent Light-Induced Retinal Degeneration in Albino BALB/c Mice
Authors: Tahia Faiza , Ma Dejian , Stephenson Daniel J. , Basu Sandip K. , Del Mar Nobel A. , Lenchik Nataliya , Kochat Harry , Brown Kennard , Chalfant Charles E. , Mandal Nawajes
Published: December 2024

Retinal degenerative diseases lead to irreversible vision loss due to photoreceptor cell death, driven by complex genetic and environmental factors. Ceramide, a sphingolipid metabolite, emerges as a critical mediator in the apoptotic cascade associated with retinal degeneration. Our previous work demonstrated L-Cycloserine’s ability to protect photoreceptor-derived cells from oxidative stress by inhibiting the de novo ceramide pathway and thus prompting further investigation on its effect in the in vivo retina. This study investigates the potential of L-Cycloserine to protect albino BALB/c mice against light-induced retinal degeneration (LIRD). L-Cycloserine, in an optimal dose, administered systemically 30 min before LIRD, was found to prevent photoreceptor cell death significantly from light-induced degeneration. We further determined the retinal bioavailability and pharmacokinetic behavior of L-Cycloserine, its effect on sphingolipid profile, expression of sphingolipid biosynthetic, and cell death-promoting genes and proteins from the retina to understand the underlying mechanisms. This study lays the groundwork for further preclinical and clinical investigations into L-Cycloserine’s potential as a novel therapeutic in treating retinal degenerative diseases.
Chondroprotective Effect of Campylaephora hypnaeoides Extract in Primary Chondrocytes and Rat OA Model
Authors: Jang Ji Yun , Lee Seul Ah , Kim Do Kyung , Lee Sook-Young , Kim Chun Sung
Published: December 2024

Campylaephora hypnaeoides (C. hypnaeoides) was extracted using fermented ethanol. The effect of fermented ethanol extract of C. hypnaeoides (FeCH) on chondrocyte viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-iphenyltetrazolium bromide assay, which showed no cytotoxicity at 2 mg/mL. FeCH pretreatment in IL-1β-stimulated chondrocytes significantly inhibited the accumulation of nitric oxide and prostaglandin E2, which was analyzed using the ELISA assay. In addition, protein expression levels of inflammatory-related factors, such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, tumor necrosis factor-alpha, and cartilage-degrading-related enzymes, such as matrix metalloproteinases-1, -3, and -13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 were significantly decreased in IL-1β-stimulated chondrocytes pretreated with FeCH, which were analyzed using western blot analysis. In addition, as a result of analyzing the content of collagen type II (Col II) and proteoglycan through western blot analysis and alcian blue staining, FeCH pretreatment prevented the degradation of Col II and proteoglycan. It was analyzed through western blot analysis that the chondroprotective effect of FeCH may be mediated through MAPKs and NF-κB-signaling mechanisms. In an in vivo study, an osteoarthritis experimental animal model with damaged medial meniscus (DMM) was utilized and orally administered daily for 8 weeks after surgery. At the study end point, knee joints were harvested and subjected to histological analysis with safranin O staining. As a result, articular cartilage was significantly protected in the FeCH group compared to the DMM group. These results suggest FeCH as a candidate material for the development of pharmaceutical materials for the treatment or prevention of degenerative arthritis.
Blocking the Sphingosine-1-Phosphate Receptor 2 (S1P2) Reduces the Severity of Collagen-Induced Arthritis in DBA-1J Mice
Authors: Lee Ju-Hyun , Lee Jung-Eun , Im Dong-Soon
Published: December 2024

The amount of sphingosine 1-phosphate (S1P) found in the synovial tissue of individuals with rheumatoid arthritis is five times greater than that in those with osteoarthritis. Our study aims to determine whether inhibiting S1P2 can mitigate collagen-induced rheumatoid arthritis (CIA) by using an S1P2 antagonist, JTE-013, alongside DBA-1J S1pr2 wild-type (WT) and knock-out (KO) mice. CIA causes increases in arthritis scores, foot swelling, synovial hyperplasia, pannus formation, proteoglycan depletion, cartilage damage, and bone erosion, but these effects are markedly reduced when JTE-013 is administered to S1pr2 WT mice. CIA also elevates mRNA expression levels of pro-inflammatory Th1/Th17 cytokines in the foot and spleen, which are significantly decreased by JTE-013 in S1pr2 WT mice. Additionally, CIA raises Th1/Th17 and Treg cell counts, while JTE-013 reduces these elevations in the spleens of S1pr2 WT mice. Treatment with JTE-013 or the absence of S1pr2 curtails the differentiation of naïve T cells into Th1 and Th17 cells in a dose-dependent manner. In SW982 human synovial cells, JTE-013 lowers LPS-induced increases in pro-inflammatory cytokine levels. Overall, these findings propose that blocking S1P2 in immune and synovial cells may alleviate rheumatoid arthritis symptoms and offer a potential therapeutic approach.
The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein
Authors: Gwozdzinski Lukasz , Pieniazek Anna , Gwozdzinski Krzysztof
Published: December 2024

This review discusses sources of reactive oxygen species, enzymatic antioxidant systems, and low molecular weight antioxidants. We present the pathology of varicose veins (VVs), including factors such as hypoxia, inflammation, dysfunctional endothelial cells, risk factors in varicose veins, the role of RBCs in venous thrombus formation, the influence of reactive oxygen species (ROS) and RBCs on VV pathology, and the role of hemoglobin in the damage of particles and macromolecules in VVs. This review discusses the production of ROS, enzymatic and nonenzymatic antioxidants, the pathogenesis of varicose veins as a pathology based on hypoxia, inflammation, and oxidative stress, as well as the participation of red blood cells in the pathology of varicose veins.
Study of Graphene Oxide and Silver Nanowires Interactions and Its Association with Electromagnetic Shielding Effectiveness
Authors: Milenković Mila , Saeed Warda , Yasir Muhammad , Sredojević Dusan , Budimir Milica , Stefanović Andjela , Bajuk-Bogdanović Danica , Jovanović Svetlana
Published: December 2024

Technological development has led to the need for materials able to block electromagnetic waves (EMWs) emitted from various devices. EMWs could negatively affect the working performance and lifetime of multiple instruments and measuring devices. New EMW shielding materials are being developed, while among nanomaterials, graphene-based composites have shown promising features. Herein, we have produced graphene oxide (GO), silver nanowires (AgNWs) composites, by varying the mass ratios of each component. UV-Vis, infrared, Raman spectroscopies, and thermogravimetric analysis proved the establishment of the interactions between them. For the first time, the strength and the nature of the interaction between GO sheets with various levels of oxidation and AgNWs were investigated using density function theory (DFT). The interaction energy between ideal graphene and AgNWs was calculated to be −48.9 kcal/mol, while for AgNWs and GO, this energy is almost doubled at −81.9 kcal/mol. The DFT results confirmed the interfacial polarization at the heterointerface via charge transfer and accumulation at the interface, improving the efficacy of EMW shielding. Our results indicated that AgNWs create a compact complex with GO due to charge transfer between them. Charge redistributions in GO-AgNWs composites resulted in an improved ability of the composite to block EMWs compared to GO alone.
Barley Seed Germination and Seedling Growth Responses to Polyethylene Glycol (PEG)-Induced Drought Stress
Authors: Davidson-Willis Matthew , Wen Guoqi , Samanfar Bahram , Khanal Raja
Published: December 2024

Drought is becoming more prevalent and negatively affects the growth and development of barley. To explore the genetic variation in barley under drought stress, ten breeding genotypes were tested using polyethylene glycol-6000 to simulate drought conditions. We observed that drought stress significantly affected germination-related traits, depending on the specific genotypes. Some parameters, such as root length, reduced by up to 85% under drought conditions compared to the control. Overall, considering the barley growth performance, the drought tolerance index was an ideal criterion for selecting drought-tolerant genotypes, as it well characterized the gradient responses of barley genotypes to drought stress. Based on this indicator, genotype OB1878-ON-50 is recommended as a significant germplasm resource for low-precipitation regions.
A Glimpse at the Future Technological Trends of Road Infrastructure: Textual Information-Based Data Retrieval
Authors: Kim Inyoung , Choi Sungtaek , Lee Hyejin , Park Jeehyung , Yun Ilsoo
Published: December 2024

Since the Fourth Industrial Revolution was announced in 2015, relevant key technologies have recently merged and have extensively affected our society. To provide empirical insights into the future and address expected issues in the context of transportation, this study seeks to investigate how future road infrastructure technology will shift. Going over the mainstream future road infrastructure inspired by the strategy implemented in the Korean New Deal 2.0, we extract central keywords explaining what specific technologies and political directions will prevail globally. In particular, a specific morphological analyzer, Mecab-Ko, which is suitable for Korean is selected after comparing a variety of packages. Then, a specific text mining approach is employed to collect textual online sources (news articles, research articles, and reports) written in Korean while most studies gather information written in English. Using the term frequency-inverse document frequency (TF-IDF), 11 keywords were extracted from unstructured textual online sources. Topic modelling with latent Dirichlet allocation (LDA) is subsequently performed to classify them into four groups: an unmanned payment system, intelligent road infrastructure, connected automated driving road, and eco-friendly road. Based on these findings, we can take a glimpse into how the future road infrastructure in Korea will be reshaped. Evidently, a digitalized road without a human component is around the corner. Fully automated systems will soon become available, and the keyword sustainability will continue to receive critical attention in the transportation sector.
Unifocalization of Major Aortopulmonary Collateral Arteries (MAPCAs) and Native Pulmonary Arteries in Infancy—Application of 3D Printing and Virtual Reality
Authors: Kolcz Jacek , Rudek-Budzynska Anna , Grandys Krzysztof
Published: December 2024

Background. Major aortopulmonary collateral arteries (MAPCAs) are rare remnants of pulmonary circulation embryological development usually associated with complex congenital anomalies of the right ventricular outflow tract and pulmonary arteries. Effective management requires surgical unifocalization of MAPCAs and native pulmonary arteries (NPAs). Traditional imaging may lack the spatial clarity needed for precise surgical planning. Aim. This study evaluated the feasibility of integrating three-dimensional (3D) printing and virtual reality (VR) into preoperative planning to improve surgical precision, team communication, and parental understanding. In a prospective cohort study, nine infants undergoing MAPCA unifocalization were included. Four patients underwent conventional imaging-based planning (control), while five were additionally assessed using VR and 3D-printed models (intervention). The outcomes measured included operative times, team confidence, collaboration, and parental satisfaction. Statistical analysis was performed using standard tests. Results. The intervention group had shorter operative and cardiopulmonary bypass times compared to the control group. Intraoperative complications were absent in the VR/3D group but occurred in the control group. Medical staff in the VR/3D group reported significantly improved understanding of anatomy, surgical preparedness, and team collaboration (p < 0.05). Parents also expressed higher satisfaction, with better comprehension of their child’s anatomy and surgical plan. Conclusions. VR and 3D printing enhanced preoperative planning, surgical precision, and communication, proving valuable for complex congenital heart surgery. These technologies offer promising potential to improve clinical outcomes and patient–family experiences, meriting further investigation in larger studies.
Application of Artificial Intelligence in Otology: Past, Present, and Future
Authors: Koyama Hajime , Kashio Akinori , Yamasoba Tatsuya
Published: December 2024

Artificial Intelligence (AI) is a concept whose goal is to imitate human intellectual activity in computers. It emerged in the 1950s and has gone through three booms. We are in the third boom, and it will continue. Medical applications of AI include diagnosing otitis media from images of the eardrum, often outperforming human doctors. Temporal bone CT and MRI analyses also benefit from AI, with segmentation accuracy improved in anatomically significant structures or diagnostic accuracy improved in conditions such as otosclerosis and vestibular schwannoma. In treatment, AI predicts hearing outcomes for sudden sensorineural hearing loss and post-operative hearing outcomes for patients who have undergone tympanoplasty. AI helps patients with hearing aids hear in challenging situations, such as in noisy environments or when multiple people are speaking. It also provides fitting information to help improve hearing with hearing aids. AI also improves cochlear implant mapping and outcome prediction, even in cases of cochlear malformation. Future trends include generative AI, such as ChatGPT, which can provide medical advice and information, although its reliability and application in clinical settings requires further investigation.
Aerodigestoscopy (ADS): The Feasibility, Safety, and Comfort of a Comprehensive Procedure for the Evaluation of Physiological Disorders of the Aerodigestive Tract
Authors: Arnold Robert J. , Bausek Nina , Gaskill Christopher S. , Johnson Lawrence F. , Aldarondo Sigfredo , Aull Cody , Midani Malik , Midani Tarek , Midani Ramiz , Brown Ashton S. , Wallace Alana
Published: December 2024

Background: Limited access to the comprehensive assessment of disorders of the upper aerodigestive tract is a barrier to care in rural health facilities. Assessment of the full aerodigestive tract requires a variety of specialists. The inability to access the necessary specialists can result in misdiagnosis, underdiagnosis, and increased associated mortality. Currently, no single differential diagnostic exam comprehensively assesses all functions of the upper aerodigestive tract to bridge this gap. The purpose of this study is to investigate the feasibility and safety of a novel procedure called ADS that can bridge this gap. Methods: Results from 18,464 ADS procedures were retrospectively analyzed for feasibility, safety and comfort. Results: 96.8% of ADS procedures were successfully completed without complication, confirming the efficacy of the procedure. Conclusions: ADS is a single procedure for the assessment of physiological functions of the upper aerodigestive tract, including swallow, voice, respiration, and cough while also screening for impaired gastric retention and obstructive sleep apnea, which may pose additional urgent and emergent airway threats. ADS may improve health outcomes in underserved populations, e.g., those in a rural community, referred to by other health professionals due to complaints of aerodigestive symptoms and signs.
Characterization of Inflammatory Bowel Disease in the Elderly According to Age of Onset
Authors: González Manuel Bracho , Olmedo Martín Raúl Vicente , Morales Bermúdez Ana Isabel , Jiménez Pérez Miguel
Published: December 2024

Background/Objectives: Elderly populations are under-represented in inflammatory bowel disease (IBD) clinical trials, with limited data on phenotype, treatment patterns, outcomes, and comorbidities. The main objective of this study was to evaluate, in an elderly cohort with IBD, demographic and disease characteristics, comorbidity, polypharmacy, and treatment patterns according to the development of IBD at or before old age. Secondarily, the same analysis was performed based on the type of IBD: ulcerative colitis (UC) or Crohn’s disease (CD). Materials and Methods: Observational, single-center, retrospective study including patients diagnosed with IBD and aged 65 years or older seen at the IBD office of the Regional University Hospital of Malaga between September and November 2022. Data were recorded on demographic, disease-related, and IBD treatment-related variables, comorbidities, and polypharmacy. A descriptive and analytical study was undertaken according to the age of IBD onset and type of IBD. Results: Of the patients included, 50.8% were male, 55.1% had CD, and 44.9% UC. IBD onset was before age 65 years in 69.5% and ≥65 years in 30.5%. Elderly with IBD who debuted <65 presented longer disease duration (19.67 ± 9.82 years) and required more IBD-related surgeries (37.8%); elderly with IBD who debuted ≥65 were older (77.69 ± 6.26 years), with no differences in the other variables. According to the type of IBD, elderly UC patients were older (74.55 ± 6.9 years), used more aminosalicylates (77.4%), and had higher rates of polypharmacy (90.6%). Elderly patients with CD had higher IBD activity (moderate/severe in 72.3%), used more biologic drugs (58.5%), and required more IBD-related surgeries (44.6%). Conclusions: Elderly patients who develop IBD before or after the age of 65 years are overall very similar in baseline and disease-related characteristics. Elderly with CD have higher IBD activity and require more biologic drugs and IBD-related surgeries. Elderly with UC are older and have higher rates of polypharmacy and aminosalicylate use.