bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Risk Assessment of Nail Technicians in the Formal and Informal Sectors of Johannesburg, South Africa
Authors: Keretetse Goitsemang , Nelson Gill , Brouwer Derk
Published: February 2025

Exposure to volatile organic compounds (VOCs) in nail salons poses risks of acute and chronic health effects for nail technicians. The objectives of this study were to investigate differences in VOC exposure and self-reported symptoms among formal and informal nail technicians and assess the non-carcinogenic and carcinogenic risks using a probabilistic approach. A questionnaire was administered to 54 formal and 60 informal nail technicians to elicit information on sociodemographic characteristics, work conditions, and self-reported symptoms. Passive sampling was employed to measure 60 personal breathing zone concentrations of VOCs among 20 nail technicians (both formal and informal) over three consecutive days, along with 29 passive samples for formaldehyde in the informal sector. All VOC concentrations, except formaldehyde, were below occupational exposure limits. Sixty percent of the informal nail technicians and fifty-two percent of the formal nail technicians reported health-related symptoms; however, the difference was not statistically significant (p > 0.05). The median and 95th percentile non-cancer risks exceeded the hazard coefficient for 2-propanol in all technicians and MMA among informal technicians. The benzene and formaldehyde cancer risk estimates (medians and 95th percentiles) exceeded the US Environmental Protection Agency cancer risk threshold of 1 × 10−6. These findings indicate that nail technicians are at risk of developing acute and chronic health effects from long-term low-level exposure to VOCs.
Stigma Toward Severe Mental Illness Among Healthcare Students: A Qualitative Study
Authors: Masedo Gutiérrez Ana Isabel , Martinez Geraldine Cedeño
Published: February 2025

Background: Individuals diagnosed with Severe Mental Illness (SMI) often perceive negative attitudes from health professionals, acting as a barrier to effective treatment. The present study explores healthcare students’ attitudes toward SMI to identify potential areas of stigma. Methods: A descriptive analytical qualitative approach was employed. Twenty-seven students from six different healthcare programs at the University of Malaga participated in semi-structured interviews, which were subsequently analyzed using thematic content analysis with the assistance of NVivo 12 software. Results: Three main themes emerged from the data: ideals, experiences with SMI, and views on hospitalization and coercive measures. Students acknowledge the importance of empathy but often feel unprepared due to limited knowledge, leading to avoidance and negative interactions. Although stigmatizing beliefs regarding dangerousness and inabilities persist, students generally reject segregation and advocate for equal rights. Positive contact experiences with mental illness can modify negative attitudes and enhance empathy, particularly among individuals with their own personal experiences. Participants generally oppose coercive measures, except for safety concerns and lack of illness awareness, advocating for alternatives to preserve autonomy. Conclusions: The study highlights that insecurity and feeling unprepared could be linked to stigmatizing and negative experiences with individuals with SMI. Therefore, we underline the need for the anti-stigma education of healthcare students focusing on contact experiences and promoting confidence in their knowledge and skills.
Molecular Advances in Abiotic Stress Signaling in Plants: Focus on Atmospheric Stressors
Authors: Labudda Mateusz , Jeandet Philippe
Published: February 2025

Plants face many abiotic stresses that significantly impact their growth and survival, requiring intricate mechanisms in order to adapt and thrive [...]
Glucose Metabolism and Tumor Microenvironment: Mechanistic Insights and Therapeutic Implications
Authors: Andryszkiewicz Wiktoria , Gąsiorowska Julia , Kübler Maja , Kublińska Karolina , Pałkiewicz Agata , Wiatkowski Adam , Szwedowicz Urszula , Choromańska Anna
Published: February 2025

Metabolic reprogramming in cancer cells involves changes in glucose metabolism, glutamine utilization, and lipid production, as well as promoting increased cell proliferation, survival, and immune resistance by altering the tumor microenvironment. Our study analyzes metabolic reprogramming in neoplastically transformed cells, focusing on changes in glucose metabolism, glutaminolysis, and lipid synthesis. Moreover, we discuss the therapeutic potential of targeting cancer metabolism, focusing on key enzymes involved in glycolysis, the pentose phosphate pathway, and amino acid metabolism, including lactate dehydrogenase A, hexokinase, phosphofructokinase and others. The review also highlights challenges such as metabolic heterogeneity, adaptability, and the need for personalized therapies to overcome resistance and minimize adverse effects in cancer treatment. This review underscores the significance of comprehending metabolic reprogramming in cancer cells to engineer targeted therapies, personalize treatment methodologies, and surmount challenges, including metabolic plasticity and therapeutic resistance.
Increased Kindlin-2 via SMURF1 Inhibition Attenuates Endothelial Permeability and Acute Lung Injury
Authors: Chen Weiguo , Epshtein Yulia , Vagts Christen , Cress Anne E. , Jacobson Jeffrey R.
Published: February 2025

Integrin β4 (ITGB4) mediates lung endothelial cell (EC) inflammation attenuated by simvastatin, an HMG CoA-reductase inhibitor. The cytoplasmic domain of ITGB4 is predicted to bind kindlin-2. Kindlin-2 expression is mediated by SMURF1, an E3 ubiquitin ligase that promotes kindlin-2 ubiquitination and degradation. We hypothesized that increased kindlin-2 expression via the inhibition of SMURF1 mediates EC inflammatory responses relevant to acute lung injury (ALI). To investigate this, human lung ECs were treated with simvastatin (5 µM, 16 h) prior to the immunoprecipitation of kindlin-2 and Western blotting for ITGB4. Next, ECs were treated with a SMURF1 inhibitor, A01, and increased kindlin-2 expression was confirmed. In assays of barrier function, kindlin-2 was silenced (siRNA) in ECs prior to thrombin and measurements of transendothelial resistance (TER) and FITC-dextran transwell flux. Repeat assessments of barrier function were performed in A01-treated ECs. Finally, mice were pretreated with A01 prior to LPS; bronchoalveolar lavage (BAL) fluid was collected, and their lungs were used for histology. Simvastatin increased ITGB4:kindlin-2 association, while A01 increased kindlin-2 expression. Thrombin-induced EC barrier disruption was both increased after kindlin-2 silencing and decreased by A01. Finally, murine ALI was significantly attenuated by A01. Our findings suggest that the augmentation of kindlin-2 may serve as a novel ALI therapeutic strategy.
Ocular Surface Changes Differ Significantly Between Oxaliplatin- and Diabetes-Induced Polyneuropathy
Authors: Schicht Martin , Sisignano Marco , Farger Jessica , Wedel Saskia , Phunchago Nichapa , Perumal Natarajan , Manicam Caroline , Scholich Klaus , Geisslinger Gerd , Paulsen Friedrich , Lütjen-Drecoll Elke
Published: February 2025

Dry eye disease (DED) is often seen in patients with polyneuropathies (PNs), but the relationship between the different forms of PNs and DED is not known. In oxaliplatin (Ox-)-treated mice with PNs, morphological changes in the sciatic nerve (SN), dorsal root ganglia (DRG), trigeminal ganglia (TG), and the ocular tissues involved in tear formation were investigated. In addition, the tear proteomics and the gene expression of related proteins in the ocular surface tissues as well as inflammatory factors were analyzed. There were significant changes in six tear proteins compared to the controls, with respective changes in gene expression in the ocular tissues. Morphologically, there was a decrease in the number of conjunctival goblet cells and changes in the myofibroblasts surrounding the Meibomian glands. The lacrimal gland appeared normal. In the SN, there was a slight decrease in the number of mitochondria without signs of inflammation. In the DRG, 30–50% of the small- and medium-sized neuronal cells had swollen mitochondria. In contrast, the mitochondria of the TG were unremarkable. The changes in the tear film proteins and the ocular tissue morphology involved in tear formation in OPN differed significantly from those previously described in DPN mice, despite a similar mechanical hypersensitivity and similar morphological features of the DRG. In DPN, these changes led to aqueous-deficient dry eye disease, whereas in OPN, they resulted in evaporative DED. Furthermore, in contrast to DPN, the TG in OPN showed no morphological alterations, which indicates differences in the peripheral nerve changes and ocular nerve damage between the two conditions.
Peptide Fractions Extracted from the Hemolymph of Hermetia illucens Inhibit Growth and Motility and Enhance the Effects of Traditional Chemotherapeutics in Human Colorectal Cancer Cells
Authors: Lucchetti Donatella , Rinaldi Roberta , Artemi Giulia , Salvia Rosanna , De Stefano Federica , Scieuzo Carmen , Falabella Patrizia , Sgambato Alessandro
Published: February 2025

Cancer is a leading cause of death worldwide, characterized by uncontrolled cell growth and multiple mutations. Chemotherapy is often associated with harmful side effects, and cancer cells may become resistant through various mechanisms. New approaches, which are able to address both the toxicity and resistance issues of chemotherapy, are of primary importance in cancer research. Antimicrobial peptides (AMPs), naturally occurring molecules in the innate immune system of all living organisms, have a wide spectrum of cytotoxic activities against cancer cells and could be a promising alternative to actual chemotherapeutics. Here, we tested peptide fractions, rich in AMPs, extracted from the hemolymph of the larvae of the insect Hermetia illucens on the HT29 and HCT116 human colorectal cancer cells, observing cell growth inhibition by cell accumulation in the G2/M phase and increased apoptosis. Furthermore, the peptide extract induced a significant cytoskeleton reorganization, resulting in reduced motility. These effects were more evident with the peptide fractions obtained from the Escherichia coli-infected larvae. The peptide fractions also enhanced the effects of traditional chemotherapeutics. Overall, the results obtained suggest the presence of biologically active molecules in the hemolymph of H. illucens larvae, confirming that insect-derived peptides are a promising research area in oncology.
Malocclusion Worsens Survival Following Sepsis Due to the Disruption of Innate and Acquired Immunity
Authors: Fujinami Yoshihisa , Saito Masafumi , Ono Yuko , Akashi Masaya , Inoue Shigeaki , Kotani Joji
Published: February 2025

Sepsis is a severe condition with high mortality, in which immune dysfunction plays a critical role. Poor oral health has been linked to frailty, but its impact on sepsis outcomes remains unclear. Therefore, we used a mouse model of malocclusion and sepsis to investigate how tooth loss affects immune responses during sepsis. Adult male C57BL/6 mice were divided into four groups: Control, Malocclusion (Mal), Sepsis (CS), and Malocclusion with Sepsis (Mal + CS). Malocclusion was induced by tooth extraction, and sepsis was induced using cecal slurry injection. We assessed survival rates, immune cell counts, and biochemical markers. The Mal + CS group exhibited significantly lower survival rates and greater weight loss compared to the CS group. The flow cytometry showed reduced neutrophils, monocytes, and T cells in the Mal + CS group. Elevated ALT and AST levels indicated liver damage. No significant differences in bacterial loads were observed, but immune suppression was exacerbated in the Mal + CS group. Malocclusion worsens sepsis outcomes by impairing both innate and adaptive immune responses. These findings emphasize the importance of oral health in improving sepsis prognosis and immune function during critical illnesses.
Changes in Mitochondrial Transcriptional Rhythms and Depression-like Behavior in the Hippocampus of IL-33-Overexpressing Mice
Authors: Li Yang , Gao Weinan , Jiao Lin , Dong Delu , Sun Liankun , Liu Yanan , Shen Luyan
Published: February 2025

Neuroinflammation is involved in the development of depression and may induce depression-like behaviors by affecting metabolism through interactions with circadian rhythms. As the hub of metabolism, mitochondria are regulated by various types of metabolism and release signals that regulate cellular functions. In this study, we performed transcriptomic analysis of the hippocampus of IL-33-overexpressing mice to provide new ideas to explore the pathogenesis of inflammation-mediated depression at the transcriptional level. Male C57BL/6J mice and IL-33-overexpressing mice were subjected to behavioral tests. The hippocampus was extracted during the light or dark period, and differential gene expression analysis was conducted using RNA sequencing. Differential gene enrichment analysis was performed, as well as multilayered analysis of mitochondrial transcriptional rhythms by integrating the regulatory networks and Mito 3.0 database. The results were further verified using RT-qPCR. IL-33-overexpressing mice exhibited depressive behaviors associated with rhythmic disorders and shortened circadian cycles. Differential KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that the top 20 pathways with the lowest p-values included mood-related, immune-related, and circadian rhythm-related pathways. Differential gene GO (Gene Ontology) enrichment analysis showed that 20 of the top 30 pathways with the lowest p-values were related to metabolism. Transcriptome data from IL-33-overexpressing mice showed that the mitochondrial-encoded subunit of the oxidative respiratory complex showed predominantly increased expression during the light period. Metabolic disorders and disrupted mitochondrial transcriptional rhythm were also observed. Weighted gene correlation network analysis showed that the circadian cycle is associated with depression-like behavior disorders. Network analysis showed that circadian-related genes were enriched in mitochondrial pathways related to metabolism and oxidative phosphorylation. Multilayer analysis of mitochondrial transcriptional rhythms using the mitochondrial database Mito 3.0 revealed that mitochondrial dynamics and surveillance pathways were the most enriched. The depressive behavior in mice caused by long-term IL-33 stimulation may be related to changes in the transcriptional rhythms of metabolism-related genes and the interaction between mitochondria and clock genes. This suggests that mitochondrial transcriptional rhythms are central to the pathogenesis of microinflammation-induced depression, further supporting the potential of mitochondria as a target for the prevention and treatment of depression.
Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Aetiology and Potential Treatments
Authors: Bansal Amolak Singh , Seton Katharine A. , Brooks Jonathan C. W. , Carding Simon R.
Published: February 2025

Systemic infection and inflammation impair mental function through a combination of altered attention and cognition. Here, we comprehensively review the relevant literature and report personal clinical observations to discuss the relationship between infection, peripheral inflammation, and cerebral and cognitive dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive dysfunction in ME/CFS could result from low-grade persistent inflammation associated with raised pro-inflammatory cytokines. This may be caused by both infectious and non-infectious stimuli and lead to altered regional cerebral blood flow accompanied by disturbed neuronal function. Immune dysregulation that manifests as a subtle immunodeficiency or the autoimmunity targeting of one or more neuronal receptors may also be a contributing factor. Efforts to reduce low-grade systemic inflammation and viral reactivation and to improve mitochondrial energy generation in ME/CFS have the potential to improve cognitive dysfunction in this highly disabling condition.
Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever
Authors: Sun Der-Shan , Lien Te-Sheng , Chang Hsin-Hou
Published: February 2025

Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.
Early-Life Stress Caused by Maternal Deprivation Impacts Dendritic Morphology of Adult Male Mouse Neocortical Interneurons
Authors: Nakhal Mohammed M. , Yassin Lidya K. , Al Houqani Shaikha , Mydeen Ayishal B. , Ibrahim Marwa F. , Shehab Safa , Allouh Mohammed Z. , Hamad Mohammad I. K.
Published: February 2025

A substantial body of research suggests that early-life stress (ELS) is associated with neuropathology in adulthood. Maternal deprivation (MD) is a commonly utilised model in mice for the study of specific neurological diseases. The appropriate growth of dendrites is essential for the optimal functioning of the nervous system. However, the impact of ELS on interneuron dendritic morphology remains unclear. To ascertain whether ELS induces alterations in the morphology of GABAergic inhibitory interneurons in layers II/III of the medial entorhinal cortex (mEC), the somatosensory cortex (SSC), the motor cortex (MC), and the CA1 region of the hippocampus (Hp), 9-day-old male GAD-67-EGFP transgenic mice were subjected to a 24 h MD. At postnatal day 60 (P60), the animals were sacrificed, and their brains were subjected to morphological analyses. The results indicated that MD affected the dendritic morphology of GABAergic interneurons. The mean dendritic length and mean dendritic segments of the examined cortical areas, except for the MC, were significantly decreased, whereas the number of primary dendrites was unaffected. Furthermore, the density of GAD67-EGFP-positive interneurons was decreased in the mEC and Hp, but not in the somatosensory and MC. The induction of ELS through MD in a developmental time window when significant morphological changes occur rendered the developing cells particularly susceptible to stress, resulting in a significant reduction in the number of surviving interneurons at the adult stage.
Tumor Regulatory Effect of 15-Hydroxyprostaglandin Dehydrogenase (HPGD) in Triple-Negative Breast Cancer
Authors: Padilla Joselyn , Lee Bok-Soon , Kim Allen , Park Yea-In , Bansal Avani , Lee Jiyoung
Published: February 2025

Prostaglandin regulation is known to play a pivotal role in tumorigenesis; however, the contributions of the prostaglandin-metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) to cancer development remain poorly understood. In this study, we investigate the effects of HPGD on cell viability, proliferation, anchorage-independent growth, and migration in triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. Overexpression of HPGD in human TNBC cells resulted in both positive and negative regulation of cell proliferation and colony formation, with these effects occurring independent of prostaglandin E2 (PGE2). In contrast, overexpression of the mouse homolog, Hpgd, in murine TNBC cells led to a consistent but modest reduction in cell viability and colony formation, indicating that HPGD activity varies depending on species and cell line context. Notably, TNBC cells expressing a mutant form of Hpgd (Hpgdmut), which lacks the ability to bind PGE2, exhibited similar functional outcomes in cell viability and colony formation as those expressing wild-type Hpgd (HpgdWT). These findings suggest that HPGD may exert its tumorigenic effects through non-enzymatic mechanisms, potentially by involving modulation of KRAS signaling in human TNBC cells. Our results highlight the diverse roles of HPGD in cancer biology, particularly in the context of TNBC, and point to non-enzymatic pathways as a significant aspect of its tumorigenic activity.
Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation
Authors: Lin Ni-Hsuan , Jian Wan-Syuan , Perng Ming-Der
Published: February 2025

Glial fibrillary acidic protein (GFAP) is classified as a type III intermediate filament protein predominantly expressed in mature astrocytes. It has the ability to self-assemble into 10 nm filaments in vitro, making it particularly valuable for elucidating the sequences essential for filament assembly. In this study, we created a series of deletion mutants targeting sequences in the N-terminal, C-terminal, and central rod domains to explore the sequences critical for the assembly of GFAP into 10 nm filaments. The impact of these deletions on filament formation was evaluated through in vitro assembly studies and transduction assays conducted with primary astrocytes. Our data revealed that deletions at the carboxy end resulted in abnormalities in either filament diameter calibration or lateral association, whereas deletions at the amino-terminal end significantly disrupted the filament assembly process, particularly restricting filament elongation. Furthermore, we discovered that the filament-forming sequences within the rod domain varied in their contributions to filament assembly and network formation. These findings enhance our understanding of the GFAP assembly process in vitro and provide a detailed mapping of the essential regions required for GFAP assembly. These insights hold significant implications for Alexander disease arising from deletion mutations in GFAP.
Juvenile Hormone and Ecdysteroids Facilitate the Adult Reproduction Through the Methoprene-Tolerant Gene and Ecdysone Receptor Gene in the Female Spodoptera frugiperda
Authors: Zhang Yan , Ding Kui-Ting , Yang Nian-Wan , Lv Zhi-Chuang , Wang Zhen-Ying , Zhang Yong-Jun , Liu Wan-Xue , Guo Jian-Yang
Published: February 2025

Insects, as the most diverse and numerous group in the animal kingdom, are at least partly dependent on the reproduction process, which is strictly regulated by the ‘classic’ insect hormones: juvenile hormone (JH), and 20-hydroxyecdysone (20E). However, the regulatory mechanism governing the reproduction of JH and 20E in Spodoptera frugiperda remains unclear. In this study, ovarian development and ovulation in female S. frugiperda were assessed through dissection of the ovaries following treatment with JH analog (JHA) and 20E. Moreover, the expression patterns of the JH-signal and 20E-signal-related genes were determined by quantitative PCR (qPCR), and RNA interference (RNAi) was used to investigate the role of JH and 20E-induced genes. Ovarian development was observed by microdissection, and JH and 20E titers were determined by ELISA. Kr-h1, Vg, and USP expression were determined by qPCR. Dissection and qPCR results showed that JHA and 20E promoted ovarian development, egg maturation, and egg laying by upregulating Methoprene-Tolerant (Met) and Ecdysone Receptor (EcR)expression. Additionally, the RNAi results showed that the injection of dsMet and dsEcR markedly delayed ovarian development, inhibited egg maturation, and halted egg production. Knockdown of Met and EcR significantly reduced JH and 20E content and inhibited the transcription of Kr-h1 and USP. These results indicate that JH and 20E facilitate adult reproduction through the methoprene-tolerant gene and ecdysone receptor gene in female S. frugiperda.
Influence of Klotho Protein Levels in Obesity and Sarcopenia: A Systematic Review
Authors: Ariadel-Cobo Diana G. , Estébanez Brisamar , González-Arnáiz Elena , García-Pérez María Pilar , Rivera-Viloria Marta , Pintor de la Maza Begoña , Barajas-Galindo David Emilio , García-Sastre Diana , Ballesteros-Pomar María D. , Cuevas María J.
Published: February 2025

The Klotho gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. Klotho protein exists in three forms: α-klotho, β-klotho and γ-klotho. The α-klotho has two isoforms: a membrane-bound form, primarily in the kidney and brain, and a secreted klotho protein present in blood, urine, and cerebrospinal fluid. Klotho functions as a co-receptor for fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. The membrane-bound form controls various ion channels and receptors, while the secreted form regulates endocrine FGFs, including FGF19 and FGF21. The interaction between β-klotho and FGF21 in muscle is critical in the development of sarcopenic obesity. This systematic review, registered in PROSPERO and conducted following PRISMA guidelines, evaluates klotho levels in individuals with obesity or sarcopenic obesity. The study includes overweight, obese, and sarcopenic obese adults compared to those with a normal body mass index. After reviewing 713 articles, 20 studies were selected, including observational, cross-sectional, cohort studies, and clinical trials. Significant associations between klotho levels and obesity, metabolic syndrome (MS), and cardiovascular risk were observed. Exercise and dietary interventions positively influenced klotho levels, which were linked to improved muscle strength and slower decline. Klotho is a potential biomarker for obesity, MS, and sarcopenic obesity. Further research is needed to explore its mechanisms and therapeutic potential.
Genome-Wide Analysis of Soybean Apyrase Gene Family and Functional Characterization of GmAPY1-4 Responses to Aluminum Stress
Authors: Yu Yanyu , Ma Shengnan , Li Lanxin , Song Zhen , Yu Lin , Tang Chunshuang , Liu Chunyan , Chen Qingshan , Xin Dawei , Wang Jinhui
Published: February 2025

Apyrases (APYs) directly regulate intra- and extra-cellular ATP homeostasis and play a key role in the process of plants adapting to various stresses. In this study, we identified and characterized soybean APY (GmAPY) family members at the genomic level. The results identified a total of 18 APYRASE homologous genes with conserved ACR domains. We conducted a bioinformatics analysis of GmAPYs, including sequence alignment, phylogenetic relationships, and conserved motifs. According to the phylogenetic and structural characteristics, GmAPYs in soybeans are mainly divided into three groups. The characteristics of these GmAPYs were systematically evaluated, including their collinearity, gene structure, protein motifs, cis-regulatory elements, tissue expression patterns, and responses to aluminum stress. A preliminary analysis of the function of GmAPY1-4 was also conducted. The results showed that GmAPY1-4 was localized in the nucleus, presenting relatively high levels in roots and root nodules and demonstrating high sensitivity and positive responses under aluminum stress circumstances. Further functional characterization revealed that the overexpression of GmAPY1-4 in hairy roots not only induced root growth under normal growth conditions but also significantly prevented root growth inhibition under aluminum stress conditions and contributed to maintaining a relatively higher fresh root weight. By contrast, RNAi interference with the expression of GmAPY1-4 in hairy roots inhibited root growth under both normal and aluminum stress conditions, but it exerted no significant influence on the dry or fresh root weight. To sum up, these findings support the significant functional role of GmAPY1-4 in root growth and the aluminum stress response. These findings not only enhance our comprehension of the aluminum stress response mechanism by identifying and characterizing the APY gene family in the soybean genome but also provide a potential candidate gene for improving aluminum tolerance in soybeans in the future.
Hesperetin-Enhanced Metformin to Alleviate Cognitive Impairment via Gut–Brain Axis in Type 2 Diabetes Rats
Authors: Zhang Danyang , He Xiaoshi , Wang Yinbo , Wang Xiaoyu , Han Xiao , Liu Haodong , Xing Yan , Jiang Bo , Xiu Zhilong , Bao Yongming , Dong Yuesheng
Published: February 2025

Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus peel, enhanced metformin’s efficacy in reducing blood sugar levels, improving insulin sensitivity, and ameliorating cognitive impairment in diabetic rats. Additionally, it reduced the required dosage of metformin to one-third of its conventional dose. Transcriptome analysis and 16S rRNA sequencing revealed that the activation of insulin and cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathways benefited from the regulation of gut microbiota and the promotion of short-chain fatty acid (SCFA) producers such as Romboutsia. Furthermore, this study demonstrated that hesperetin supplementation counteracted the upregulation of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a pathological factor of Alzheimer’s disease (AD) that was induced by metformin. Our findings reveal that hesperetin can be used in supplementary treatment for cognitive impairment associated with diabetes.
Neurodegenerative Disease: From Molecular Basis to Therapy, 2nd Edition
Authors: Ricci Claudia
Published: February 2025

Neurodegenerative diseases, characterised by the progressive degeneration of neurons, are a heterogeneous group of largely age-related disorders that affect millions of people worldwide [...]
Molecular Biological Comparison of Pulp Stem Cells from Supernumerary Teeth, Permanent Teeth, and Deciduous Teeth for Endodontic Regeneration
Authors: Lu Hui , Shi Fangyang , Wang Boqun , Zheng Yexin , Lu Jiaxuan , Zeng Binghui , Zhao Wei
Published: February 2025

Supernumerary tooth-derived pulp stem cells (SNTSCs) hold promise for endodontic regeneration, yet little is known about the similarities and diversities of SNTSCs relative to other dental-derived mesenchymal stem cells. Herein, we compare the biological characteristics of SNTSCs with dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED). Cell proliferation, migration, and odontogenic differentiation potential, as well as viability and aging-related phenotype after long-term storage, were evaluated. Additionally, gene expressions during induced odontogenic differentiation were profiled by transcriptome sequencing. Our findings indicated that the SNTSCs outperformed the DPSCs but were inferior to the SHED in cell proliferation. The SNTSCs exhibited comparable migratory capacity to the SHED and surpassed the DPSCs. Of particular interest, the odontogenic differentiation potential followed the pattern of SHED > SNTSCs > DPSCs. After two years of storage, the SNTSCs showed weakness in resistance to apoptosis induced by lipopolysaccharide, whereas difference between the SNTSCs and SHED in stemness and senescence was not obvious. Transcriptome analysis revealed that upregulated genes in the SNTSCs were particularly enriched in inflammatory signaling pathways compared to both the DPSCs and SHED. Collectively, SNTSCs share many satisfactory features in proliferation and differentiation with SHED, which may serve as a promising alternative cell source for endodontic regeneration.
Biosynthesis of Gold Nanostructures and Their Virucidal Activity Against Influenza A Virus
Authors: Contreras Fernanda , Rivero Katherine , Rivas-Pardo Jaime Andrés , Liendo Fabiana , Segura Rodrigo , Neira Nicole , Arenas-Salinas Mauricio , Cortez-San Martín Marcelo , Arenas Felipe
Published: February 2025

Bacteria in natural environments often encounter high concentrations of metal ions, leading to the development of defense mechanisms such as chemical reduction. This process can result in the formation of nanostructures (NS) ranging from 1–100 nm, which have valuable properties for various applications, including as virucidal agents. Currently, metallic NS with virucidal activity are used in disinfectants and surface protection products. However, their production mainly relies on physical and chemical methods, which are often complex, toxic, and energy-intensive. A sustainable alternative is the biosynthesis of nanostructures. Our research focuses on the biosynthesis of gold nanostructures (AuNS) using environmental bacteria and their proteins, with the aim of exploring their potential as agents to destroy the influenza A virus. We screened bacteria under conditions with HAuCl4, identifying eight microorganisms capable of growing in high gold concentrations. Staphylococcus haemolyticus BNF01 showed the highest resistance and Au(III) reduction, growing up to 0.25 mM in HAuCl4. Bioinformatic analysis revealed five proteins with potential Au(III)-reductase activity, which were cloned and expressed in Escherichia coli. These proteins reduced gold to form AuNPs, which were purified, characterized for size, shape, and surface charge, and tested against influenza A, showing significant virucidal effects, likely due to interactions with viral proteins.
Advances in Immunotherapy in Hepatocellular Carcinoma
Authors: Bloom Matthew , Podder Sourav , Dang Hien , Lin Daniel
Published: February 2025

Over the past several years, the therapeutic landscape for patients with advanced, unresectable, or metastatic hepatocellular carcinoma has been transformed by the incorporation of checkpoint inhibitor immunotherapy into the treatment paradigm. Frontline systemic treatment options have expanded beyond anti-angiogenic tyrosine kinase inhibitors, such as sorafenib, to a combination of immunotherapy approaches, including atezolizumab plus bevacizumab and durvalumab plus tremelimumab, both of which have demonstrated superior response and survival to sorafenib. Additionally, combination treatments with checkpoint inhibitors and tyrosine kinase inhibitors have been investigated with variable success. In this review, we discuss these advances in systemic treatment with immunotherapy, with a focus on understanding both the underlying biology and mechanism of these strategies and their efficacy outcomes in clinical trials. We also review challenges in identifying predictive biomarkers of treatments and discuss future directions with novel immunotherapy targets.
The Small Molecules of Plant Origin with Anti-Glioma Activity
Authors: Liu Xin , Su Yin-Xiao , Yang Yun-Mei , Li Rong-Tao , Zhang Zhi-Jun
Published: February 2025

Gliomas, originating from glial cells, are prevalent and aggressive brain tumors with high recurrence rates and poor prognosis. Despite advancements in surgical, radiation, and chemotherapeutic treatments, the survival rates remain low. Current standard therapies, such as Temozolomide, have limitations due to cytotoxicity, restricted effectiveness, and severe side effects. So, the development of safer anti-glioma agents is the need of the hour. Bioactive compounds of plant origin, either natural or synthetic, have potential implications due to them actively attacking different targets with a wide range of bioactivities, including anti-glioma activities. In this review, for the first time, there is an overall overview of 51 small molecules of plant origin and seven of their synthetic derivatives, represented as anti-glioma agents in the past decades. The goal of the present review is to provide a summary to comprehend the anti-glioma effects of these compounds in addition to providing a reference for preclinical research into novel anti-glioma agents for future clinical application.
Prognostic Biomarkers in Breast Cancer via Multi-Omics Clustering Analysis
Authors: Malighetti Federica , Villa Matteo , Villa Alberto Maria , Pelucchi Sara , Aroldi Andrea , Cortinovis Diego Luigi , Canova Stefania , Capici Serena , Cazzaniga Marina Elena , Mologni Luca , Ramazzotti Daniele , Cordani Nicoletta
Published: February 2025

Breast cancer (BC) is a highly heterogeneous disease with diverse molecular subtypes, which complicates prognosis and treatment. In this study, we performed a multi-omics clustering analysis using the Cancer Integration via MultIkernel LeaRning (CIMLR) method on a large BC dataset from The Cancer Genome Atlas (TCGA) to identify key prognostic biomarkers. We identified three genes—LMO1, PRAME, and RSPO2—that were significantly associated with poor prognosis in both the TCGA dataset and an additional dataset comprising 146 metastatic BC patients. Patients’ stratification based on the expression of these three genes revealed distinct subtypes with markedly different overall survival (OS) outcomes. Further validation using almost 2000 BC patients’ data from the METABRIC dataset and RNA sequencing data from therapy-resistant cell lines confirmed the upregulation of LMO1 and PRAME, respectively, in patients with worse prognosis and in resistant cells, also suggesting their potential role in drug resistance. Our findings highlight LMO1 and PRAME as potential biomarkers for identifying high-risk BC patients and informing targeted treatment strategies. This study provides valuable insights into the multi-omics landscape of BC and underscores the importance of personalized therapeutic approaches based on molecular profiles.
Comparison of Staphylococcus pettenkoferi Isolated from Human Clinical Cases and Cat Carriers Regarding Antibiotic Susceptibility and Biofilm Production
Authors: Bierowiec Karolina , Delmar Ashley , Karwańska Magdalena , Siedlecka Magdalena , Kumala-Ćwikła Aleksandra , Książczyk Marta , Kapczyńska Katarzyna
Published: February 2025

Staphylococcus pettenkoferi (S. pettenkoferi) is a rare opportunistic bacterium not commonly found in healthy individuals or animals. S. pettenkoferi has increasing clinical significance in both veterinary and human medicine due to its multidrug resistance and biofilm-forming ability. This study analyzed 12 isolates of S. pettenkoferi collected from humans and cats and identified them using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA and partial rpoB gene sequencing. All of the S. pettenkoferi were phenotypically resistant to penicillin, and almost all (except one human strain) were resistant to methicillin. Antibiotic susceptibility testing revealed a high prevalence of multidrug resistance in all human strains with frequent resistance to β-lactams, macrolides, and tetracyclines. A comparative analysis of human and feline isolates indicated the presence of shared resistance genes such as blaZ, mecA, and ermA. Biofilm production varied across isolates, with more potent biofilm formation abilities observed at elevated temperatures (39 °C) and time (48 h). These findings underscore the potential zoonotic risks of S. pettenkoferi and its role in managing multidrug-resistant infections.
Anti-Cancer and Pro-Immune Effects of Lauric Acid on Colorectal Cancer Cells
Authors: Mori Shiori , Fujiwara-Tani Rina , Ogata Ruiko , Ohmori Hitoshi , Fujii Kiyomu , Luo Yi , Sasaki Takamitsu , Nishiguchi Yukiko , Bhawal Ujjal Kumar , Kishi Shingo , Kuniyasu Hiroki
Published: February 2025

Lauric acid (LAA) is a 12-carbon medium-chain fatty acid that reportedly has antitumor and muscle-protecting effects. However, the details of these antitumor effects remain unclear. Therefore, in this study, we investigated the mechanism underlying the antitumor effects of LAA in CT26 and HT29 colorectal cancer (CRC) cell lines. Our in vitro findings demonstrated that LAA suppressed CRC cell proliferation, induced mitochondrial oxidative stress (reactive oxygen species (ROS)), inhibited oxidative phosphorylation (OXPHOS), and induced apoptosis. Moreover, in vivo analysis of LAA showed a more pronounced antitumor effect in CT26 cells in a syngeneic mouse tumor model than in vitro; therefore, we further investigated its impact on host antitumor immunity. We observed that LAA increased the number of effector T cells in mouse tumors, while in vitro LAA activated mouse splenocytes (SplC) and promoted OXPHOS. In two-dimensional co-culture of SplC and CT26 cells, LAA induced cell death in cancer cells. In three-dimensional co-culture, LAA promoted SplC infiltration and suppressed the formation of tumor spheres. Thus, LAA may exert antitumor effects through increased ROS production in cancer cells and effector T cell activation via increased energy metabolism. These results suggest that LAA, when used in combination with existing anti-cancer drugs, is likely to exhibit sensitizing effects in terms of both antitumor and antitumor immune effects, and future clinical studies are anticipated.
Hydrophilic Sulfonate Covalent Organic Frameworks for Serum Glycopeptide Profiling
Authors: Yang Shishu , Jiang Yuheng , Jiang Shijie , Liu Lihong , Liu Si , Zhang Hua , Gu Zhiyuan
Published: February 2025

Aberrant protein glycosylation is closely associated with a number of biological processes and diseases. However, characterizing the types of post-translational modifications (PTMs) from the complex biological samples is challenging for comprehensive glycoproteomic analysis. The development of high-performance enrichment materials and strategies during the sample pretreatment process is a prerequisite to glycoproteome research. Here in this work, a sulfonate-rich covalent organic framework (COF) called TpPa-(SO3H)2 (referred to as SCOF-2) was synthesized using the Schiff base reaction for the identification of glycopeptides. Benefiting from high hydrophilicity and abundant sulfonate affinity, a total of 28 and 16 glycopeptides could be efficiently detected from the standard glycoproteins of horseradish peroxidase (HRP) and immunoglobulin G (IgG) tryptic digest, respectively. Moreover, the as-prepared sulfonate-rich SCOF-2 has an ultralow detection limit (0.01 fmol μL−1), excellent enrichment selectivity (molar ratio HRP:BSA = 1:5000), satisfactory recovery rate (89.1%), high adsorption capacity (150 mg g−1) and good reusability in the individual enrichment. Meanwhile, by using the SCOF-2 adsorbent, 196 and 194 endogenous glycopeptides in the serum of ovarian cancer patients and healthy people among triplicates were successfully enriched and identified, respectively, using combined nanoLC–MS/MS technology. It demonstrated its great application potential in glycoproteomics research and provided a novel insight for the design of affinity materials.
Techniques for Transversal Skill Classification and Relevant Keyword Extraction from Job Advertisements
Authors: Gavrilescu Marius , Leon Florin , Minea Alina-Adriana
Published: February 2025

The recognition of transversal skills from job ads is important for ensuring a proper match between potential candidates and the requirements formulated in job ad texts. We contribute to understanding and interpreting job ad phrasings in two significant ways: firstly, we propose neural network-based classification models for the recognition of the six fundamental transversal skills formulated within the European Skills, Competences, Qualifications, and Occupations (ESCO) platform; secondly, we develop a means of identifying meaningful terms relevant to each transversal skill class, using feature importance-scoring methods that highlight the relevance of the words for recognizing each transversal skill. The resulting pipeline allows for the identification of skills in job ad texts, as well as the highlighting of important key terms for each recognized skill, therefore contributing to a better understanding of the skill taxonomy as well as the correlation of the related skill base with the corresponding formulations from job ads.
Epigenetic Age in Prader–Willi Syndrome and Essential Obesity: A Comparison with Chronological and Vascular Ages
Authors: Rigamonti Antonello E. , Bollati Valentina , Albetti Benedetta , Caroli Diana , Bondesan Adele , Grugni Graziano , Cella Silvano G. , Sartorio Alessandro
Published: February 2025

Background: Prader–Willi syndrome (PWS) is a rare genetic disorder mapping to the imprinted 15q11-13 locus, specifically at the paternally expressed snord116 region, which has been implicated in controlling epigenetic mechanisms. Some aspects of the PWS-related clinical phenotype, such as the high mortality rate in adulthood, might be attributed to accelerated epigenetic ageing. Objectives: The aim of the present case–control study was to evaluate epigenetic age, age acceleration, vascular age (VA), and vascular ageing in adults with PWS (n = 24; F/M = 11/13; age = 36.8 [26.6; 45.3] years; body mass index, BMI = 36.8 [33.9; 44.8] kg/m2), compared with a sex- and age-matched group of subjects with essential obesity (EOB) (n = 36; F/M = 19/17; age = 43.4 [30.6; 49.5] years; BMI = 44.8 [41.2; 51.7] kg/m2). Results: In subjects with PWS, there was a younger epigenetic age and a lower age acceleration than in subjects with EOB. No differences were found between VA and vascular ageing in the two groups. Epigenetic age was associated with chronological age and VA within each group. For each group, no relevant associations of epigenetic age or age acceleration with demographic, biochemical, and clinical parameters were found. When considering individuals with PWS, there were no associations of epigenetic age with growth hormone (GH) deficiency, duration of hormone replacement therapy, and plasma levels of insulin-like growth factor 1 (IGF-1). Conclusions: The hypothesis of accelerated epigenetic ageing in PWS should be rejected. Additionally, considering the existence of a SNORD116-dependent epigenetic dysregulation in PWS, the results of the present study might be misleading, since an epigenetics-based approach was used to measure ageing.