Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (245)

Search Parameters:
Keywords = SoxB

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
21 pages, 632 KiB  
Review
DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives—A Narrative Review
by Dragoş Puia, Marius Ivănuță and Cătălin Pricop
Int. J. Mol. Sci. 2025, 26(15), 7507; https://doi.org/10.3390/ijms26157507 (registering DOI) - 3 Aug 2025
Abstract
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current [...] Read more.
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article
(This article belongs to the Section Molecular Oncology)
Show Figures

Figure 1

24 pages, 528 KiB  
Review
Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review
by Ioana Cristina Rotar, Elena Bernad, Liviu Moraru, Viviana Ivan, Adrian Apostol, Sandor Ianos Bernad, Daniel Muresan and Melinda-Ildiko Mitranovici
Diagnostics 2025, 15(15), 1872; https://doi.org/10.3390/diagnostics15151872 - 25 Jul 2025
Viewed by 221
Abstract
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are [...] Read more.
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are involved in tumor initiation and development, metastasis, and recurrence. Method. A narrative review of significant scientific publications related to the topic and its applicability in endometrial cancer (EC) was performed with the aim of identifying current knowledge about the identification of CSC populations in endometrial cancer, their biological significance, prognostic impact, and therapeutic targeting. Results: Therapy against the tumor population alone has no or negligible effect on CSCs. CSCs, due to their stemness and therapeutic resistance, cause tumor relapse. They target CSCs that may lead to noticeable persistent tumoral regression. Also, they can be used as a predictive marker for poor prognosis. Reverse transcription–polymerase chain reaction (RT-PCR) demonstrated that the cultured cells strongly expressed stemness-related genes, such as SOX-2 (sex-determining region Y-box 2), NANOG (Nanog homeobox), and Oct 4 (octamer-binding protein 4). The expression of surface markers CD133+ and CD44+ was found on CSC as stemness markers. Along with surface markers, transcription factors such as NF-kB, HIF-1a, and b-catenin were also considered therapeutic targets. Hypoxia is another vital feature of the tumor environment and aids in the maintenance of the stemness of CSCs. This involves the hypoxic activation of the WNT/b-catenin pathway, which promotes tumor survival and metastasis. Specific antibodies have been investigated against CSC markers; for example, anti-CD44 antibodies have been demonstrated to have potential against different CSCs in preclinical investigations. Anti-CD-133 antibodies have also been developed. Targeting the CSC microenvironment is a possible drug target for CSCs. Focusing on stemness-related genes, such as the transcription pluripotency factors SOX2, NANOG, and OCT4, is another therapeutic option. Conclusions: Stemness surface and gene markers can be potential prognostic biomarkers and management approaches for cases with drug-resistant endometrial cancers. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
Show Figures

Figure 1

29 pages, 23179 KiB  
Article
Oligodendrocyte-Specific STAT5B Overexpression Ameliorates Myelin Impairment in Experimental Models of Parkinson’s Disease
by Yibo Li, Zhaowen Su, Jitong Zhai, Qing Liu, Hongfang Wang, Jiaxin Hao, Xiaofeng Tian, Jiamin Gao, Dandan Geng and Lei Wang
Cells 2025, 14(15), 1145; https://doi.org/10.3390/cells14151145 - 25 Jul 2025
Viewed by 432
Abstract
Background: Parkinson’s disease (PD) involves progressive dopaminergic neuron degeneration and motor deficits. Oligodendrocyte dysfunction contributes to PD pathogenesis through impaired myelination. Methods: Single-nucleus RNA sequencing (snRNA-seq) of PD mice revealed compromised oligodendrocyte differentiation and STAT5B downregulation. Pseudotemporal trajectory analysis via Monocle2 demonstrated impaired [...] Read more.
Background: Parkinson’s disease (PD) involves progressive dopaminergic neuron degeneration and motor deficits. Oligodendrocyte dysfunction contributes to PD pathogenesis through impaired myelination. Methods: Single-nucleus RNA sequencing (snRNA-seq) of PD mice revealed compromised oligodendrocyte differentiation and STAT5B downregulation. Pseudotemporal trajectory analysis via Monocle2 demonstrated impaired oligodendrocyte maturation in PD oligodendrocytes, correlating with reduced myelin-related gene expression (Sox10, Plp1, Mbp, Mog, Mag, Mobp). DoRothEA-predicted regulon activity identified STAT5B as a key transcriptional regulator. Results: Oligodendrocyte-specific STAT5B activation improved myelin integrity, as validated by Luxol Fast Blue staining and transmission electron microscopy; attenuated dopaminergic neuron loss; and improved motor function. Mechanistically, STAT5B binds the MBP promoter to drive transcription, a finding confirmed by the luciferase assay, while the DNMT3A-mediated hypermethylation of the STAT5B promoter epigenetically silences its expression, as verified by MethylTarget sequencing and methylation-specific PCR. Conclusions: DNMT3A inhibited the expression of STAT5B by affecting its methylation, which reduced the transcription of MBP, caused oligodendrocyte myelin damage, and eventually led to dopamine neuron damage and motor dysfunction in an MPTP-induced mouse model. This DNMT3A-STAT5B-MBP axis underlies PD-associated myelin damage, connecting epigenetic dysregulation with oligodendrocyte dysfunction and subsequent PD pathogenesis. Full article
Show Figures

Graphical abstract

20 pages, 3758 KiB  
Article
Metagenomic Sequencing Revealed the Effects of Different Potassium Sulfate Application Rates on Soil Microbial Community, Functional Genes, and Yield in Korla Fragrant Pear Orchard
by Lele Yang, Xing Shen, Linsen Yan, Jie Li, Kailong Wang, Bangxin Ding and Zhongping Chai
Agronomy 2025, 15(7), 1752; https://doi.org/10.3390/agronomy15071752 - 21 Jul 2025
Viewed by 346
Abstract
Potassium fertilizer management is critical for achieving high yields of Korla fragrant pear, yet current practices often overlook or misuse potassium inputs. In this study, a two-year field experiment (2023–2024) was conducted with 7- to 8-year-old pear trees using four potassium levels (0, [...] Read more.
Potassium fertilizer management is critical for achieving high yields of Korla fragrant pear, yet current practices often overlook or misuse potassium inputs. In this study, a two-year field experiment (2023–2024) was conducted with 7- to 8-year-old pear trees using four potassium levels (0, 75, 150, and 225 kg/hm2). Metagenomic sequencing was employed to assess the effects on soil microbial communities, sulfur cycle functional genes, and fruit yield. Potassium treatments significantly altered soil physicochemical properties, the abundance of sulfur cycle functional genes, and fruit yield (p < 0.05). Increasing application rates significantly elevated soil-available potassium and organic matter while reducing pH (p < 0.05). Although alpha diversity was unaffected, NMDS analysis revealed differences in microbial community composition under different treatments. Functional gene analysis showed a significant decreasing trend in betB abundance, a peak in hpsO under K150, and variable patterns for soxX and metX across treatments (p < 0.05). All potassium applications significantly increased yield relative to CK, with K150 achieving the highest yield (p < 0.05). PLS-PM analysis indicated significant positive associations between potassium rate, nutrient availability, microbial abundance, sulfur cycling, and yield, and a significant negative association with pH (p < 0.05). These results provide a foundation for optimizing potassium fertilizer strategies in Korla fragrant pear orchards. It is recommended that future studies combine metagenomic and metatranscriptomic approaches to further elucidate the mechanisms linking potassium-driven microbial functional changes to improvements in fruit quality. Full article
(This article belongs to the Section Soil and Plant Nutrition)
Show Figures

Figure 1

23 pages, 1028 KiB  
Review
Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment
by Leonor Barroso, Pedro Veiga, Joana Barbosa Melo, Isabel Marques Carreira and Ilda Patrícia Ribeiro
Biology 2025, 14(7), 842; https://doi.org/10.3390/biology14070842 - 10 Jul 2025
Viewed by 567
Abstract
Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety [...] Read more.
Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. Full article
(This article belongs to the Section Cancer Biology)
Show Figures

Figure 1

27 pages, 4850 KiB  
Review
Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer
by Mohammad Esfini Farahani, Yanquan Zhang, Amos Olalekan Akinyemi, Fatemeh Seilani, Md Rakibul Alam and Xiaoqi Liu
Biomedicines 2025, 13(7), 1642; https://doi.org/10.3390/biomedicines13071642 - 4 Jul 2025
Viewed by 600
Abstract
Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)—plays a [...] Read more.
Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)—plays a crucial role in therapeutic resistance and disease progression. OCT4, in coordination with SOX2 and NANOG, acts as a master regulator of stemness and is frequently upregulated in prostate cancer stem cells (PCSCs). This upregulation contributes to tumor initiation, metastasis, and resistance to both androgen deprivation therapy (ADT) and chemotherapy. In this review, we explore the role of OCT4 in mediating lineage plasticity in prostate cancer, with particular emphasis on its involvement in treatment resistance and neuroendocrine differentiation. We also examine therapeutic strategies aimed at targeting OCT4 directly, such as microRNA-mediated suppression, small-molecule inhibitors, and suicide gene therapy, as well as indirect approaches that modulate OCT4 expression via FGFR and NF-κB signaling pathways. While these strategies offer promising avenues, challenges such as adaptive resistance and the intricate signaling networks within PCSCs remain significant hurdles. A deeper understanding of the molecular mechanisms underlying OCT4-driven plasticity may pave the way for novel therapeutic approaches and improved outcomes in advanced prostate cancer. Full article
(This article belongs to the Special Issue Molecular Biomarkers of Tumors: Advancing Genetic Studies)
Show Figures

Figure 1

21 pages, 2099 KiB  
Article
Identifying Molecular Modulators of the Vascular Invasion in Rectal Carcinoma: Role of ADAMTS8 and Its Co-Dependent Genes
by Bojana Kožik, Tarik Čorbo, Naris Pojskić, Ana Božović, Lidija Todorović, Ana Kolaković, Vesna Mandušić and Lejla Pojskić
Int. J. Mol. Sci. 2025, 26(13), 6261; https://doi.org/10.3390/ijms26136261 - 28 Jun 2025
Viewed by 957
Abstract
Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways [...] Read more.
Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways most likely associated with VI in rectal carcinoma. As ADAMTS8 showed statistically significant negative relations with the VI in RC patients, we further analyzed its top co-dependent genes—DNAL4, EVI2B, PPP1R35, PTGR3, RPL21, SOX4, and ZNF3—for the experimentally proven molecular modulators. We identified a total of 23 compounds from the Comparative Toxicogenomics Database based on previously reported data for all eight target genes. The search was expanded to include additional chemical agents by structure similarity using the PubChem database, which revealed 9661 additional compounds. These were subsequently used for molecular interaction analysis against target proteins co-expressed with, or associated with, ADAMTS8 in RC with VI. Ultimately, we identified four high-affinity compounds—cyanoginosin LR, doxorubicin, benzo[a]pyrene, and dibenzo(a,e)pyrene—that interacted with all target proteins. These compounds show potential for further assessment of their role in modulating processes related to vascular invasion, which is a strong negative predictor of RC outcomes. Full article
(This article belongs to the Special Issue Genomics and Proteomics of Cancer)
Show Figures

Figure 1

25 pages, 7791 KiB  
Article
Argan Callus Extract Restores Skin Cells via AMPK-Dependent Regulation of Energy Metabolism, Autophagy, and Inflammatory Pathways
by Ramona Hartinger, Felix Quirin Fenzl, Vanessa Martina Nalewaja and Karima Djabali
Antioxidants 2025, 14(7), 804; https://doi.org/10.3390/antiox14070804 - 28 Jun 2025
Viewed by 650
Abstract
Skin aging is driven by cellular senescence, oxidative stress, and diminished regenerative capacity. In this study, we investigated the effects of PhytoCellTec™ Argan, an argan callus extract (PC), on primary human fibroblasts and adult stem cells. PC treatment (0.1% and 0.5%) significantly enhanced [...] Read more.
Skin aging is driven by cellular senescence, oxidative stress, and diminished regenerative capacity. In this study, we investigated the effects of PhytoCellTec™ Argan, an argan callus extract (PC), on primary human fibroblasts and adult stem cells. PC treatment (0.1% and 0.5%) significantly enhanced fibroblast proliferation, reduced senescence-associated β-galactosidase activity, and decreased the expression of p16, p21, and phosphorylated NFκB. PC treatment lowered intracellular ROS levels, increased ATP production, and promoted autophagy via LC3B-II accumulation and p62 reduction. In skin-derived precursor cells (SKPs), as well as mesenchymal stem cells (MSCs), PC treatment improved spheroid formation and growth while preserving the expression of key stemness markers, including Sox2, Oct4, and Nestin. Furthermore, PC exhibited antioxidant capacity (TEAC assay) and inhibited elastase, supporting its anti-aging potential. These findings suggest that PC is safe at concentrations below 1% and may serve as an effective natural compound to restore cellular homeostasis, reduce senescence and inflammation, and support stem cell health during aging. Full article
Show Figures

Figure 1

24 pages, 6213 KiB  
Article
Transmembrane Protease Serine 11B Modulates Lactate Transport Through SLC16A1 in Pancreatic Ductal Adenocarcinoma—A Functional Link to Phenotype Heterogeneity
by Dinara Baiskhanova, Maike Menzel, Claudia Geismann, Christoph Röcken, Eric Beitz, Susanne Sebens, Anna Trauzold and Heiner Schäfer
Int. J. Mol. Sci. 2025, 26(11), 5398; https://doi.org/10.3390/ijms26115398 - 4 Jun 2025
Viewed by 625
Abstract
Tumor cell heterogeneity, e.g., in stroma-rich pancreatic ductal adenocarcinoma (PDAC), includes a differential metabolism of lactate. While being secreted as waste product by most cancer cells characterized by the glycolytic Warburg metabolism, it is utilized by a subset of highly malignant cancer cells [...] Read more.
Tumor cell heterogeneity, e.g., in stroma-rich pancreatic ductal adenocarcinoma (PDAC), includes a differential metabolism of lactate. While being secreted as waste product by most cancer cells characterized by the glycolytic Warburg metabolism, it is utilized by a subset of highly malignant cancer cells running the reverse Warburg metabolism. Key drivers of lactate transport are the carrier proteins SLC16A1 (import/export) and SLC16A3 (export). Expression and function of both carriers are controlled by the chaperone Basigin (BSG), which itself is functionally controlled by the transmembrane protease serine 11B (TMPRSS11B). In this study we explored the impact of TMPRSS11B on the phenotype of PDAC cells under reverse Warburg conditions. Amongst a panel of PDAC cell lines, Panc1 and BxPc3 cells were identified to express TMPRSS11B at a high level, whilst other cell lines such as T3M4 did not. ShRNA-mediated TMPRSS11B knock-down in Panc1 and BxPc3 cells enhanced lactate import through SLC16A1, as shown by GFP/iLACCO1 lactate uptake assay, whereas TMPRSS1B overexpression in T3M4 dampened SLC16A1-driven lactate uptake. Moreover, knock-down and overexpression of TMPRSS11B differentially impacted proliferation and chemoresistance under reverse Warburg conditions in Panc1 or BxPc3 and T3M4 cells, respectively, as well as their stemness properties indicated by altered colony formation rates and expression of the stem cell markers Nanog, Sox2, KLF4 and Oct4. These effects of TMPRSS11B depended on both SLC16A1 and BSG as shown by gene silencing. Immunohistochemical analysis revealed a reciprocal expression of TMPRSS11B and BSG together with SLC16A1 in some areas of tumor tissues from PDAC patients. Those regions exhibiting low or no TMPRSS11B expression but concomitant high expression of SLC16A1 and BSG revealed greater amounts of KLF4. In contrast, other tumor areas exhibiting high expression of TMPRSS11B together with BSG and SLC16A1 were largely negative for KLF4 expression. Thus, the differential expression of TMPRSS11B adds to metabolic heterogeneity in PDAC and its absence supports the reverse Warburg metabolism in PDAC cells by the enhancement of BSG-supported lactate uptake through SLC16A1 and subsequent phenotype alterations towards greater stemness. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Pancreatic Cancer: 2nd Edition)
Show Figures

Figure 1

35 pages, 1408 KiB  
Article
Feasibility and Cost-Benefit Analysis of Methanol as a Sustainable Alternative Fuel for Ships
by Pei-Chi Wu and Cherng-Yuan Lin
J. Mar. Sci. Eng. 2025, 13(5), 973; https://doi.org/10.3390/jmse13050973 - 17 May 2025
Cited by 1 | Viewed by 1348
Abstract
The amendment to MARPOL Annex VI, which limits the sulfur content in marine fuels to a maximum of 0.5 wt.%, came into effect in January 2020. This includes reducing sulfur oxide (SOX) emissions and establishing nitrogen oxide (NOX) emission [...] Read more.
The amendment to MARPOL Annex VI, which limits the sulfur content in marine fuels to a maximum of 0.5 wt.%, came into effect in January 2020. This includes reducing sulfur oxide (SOX) emissions and establishing nitrogen oxide (NOX) emission standards (Tiers I, II, and III) based on the ship’s engine type and construction date. Furthermore, the regulations require oil tankers to control volatile organic compound (VOC) emissions and prohibit the installation of new equipment containing ozone-depleting substances. After a four-year exploration phase, global shipping companies still lack consistent evaluation criteria for the selection and use of alternative fuels, resulting in divergence across the industry. According to the latest data, methanol can reduce NOX, SOX, and particulate matter (PM) emissions by approximately 80%, 99%, and 95%, respectively, compared to traditional heavy fuel oil. Furthermore, green methanol has the potential for near-zero greenhouse gas emissions and can meet the stringent standards of Emission Control Areas. Therefore, this study adopts a cost-benefit analysis method to evaluate the feasibility and implementation benefits of two promising strategies: methanol dual fuel and very low-sulfur fuel oil (VLSFO). A 6600-TEU container ship was selected as a representative case, and the evaluation was conducted by replacing an older ship with a newly built one. The reductions in total pollutants and CO2-equivalent emissions of the container ship, as well as the cost-effectiveness of each specific strategy, were calculated. This study found that, in the first five years of operation, the total incremental cost of Vessel A, which uses 100% VLSFO, will be significantly lower than that of Vessel B, which uses a blend of 30% e-methanol + 70% VLSFO as fuel. Furthermore, compared to a scenario without any improvement strategies, the total incremental cost for Vessels A and B will increase by 69.90% and 178.15%, respectively, over five years. Vessel B effectively reduced the total greenhouse gas emission equivalent (CO2e) of CO2, CH4, and N2O by 24.72% over five years, while Vessel A reduced the CO2e amount by 12.18%. Furthermore, the cost-benefit ratio (CBR) based on total pollutant emission reduction is higher for Vessel A than for Vessel B within five years of operation. However, in terms of the cost-effectiveness of CO2e emission reduction, the CBR of Vessel A becomes lower than Vessel B after 4.7 years of operation. Therefore, Vessel A’s strategy should be considered a short-term option for reducing CO2e within 4.7 years, whereas the strategy of Vessel B is more suitable as a long-term solution for more than 4.7 years. Full article
(This article belongs to the Section Marine Environmental Science)
Show Figures

Figure 1

21 pages, 8909 KiB  
Article
Isolation, Sphalerite Bioleaching, and Whole Genome Sequencing of Acidithiobacillus ferriphilus QBS3 from Zinc-Rich Sulfide Mine Drainage
by Kan Wang, Yuandong Liu, Run Liu, Wissal Belqadi, Weimin Zeng, Runlan Yu and Xueling Wu
Life 2025, 15(5), 792; https://doi.org/10.3390/life15050792 - 15 May 2025
Cited by 1 | Viewed by 527
Abstract
The genus Acidithiobacillus has been widely used in bioleaching, and novel strains in this genus, such as A. ferriphilus, have also been confirmed to possess bioleaching capabilities. In this study, an Acidithiobacillus ferriphilus strain, QBS3, was isolated from zinc-rich sulfide mine drainage [...] Read more.
The genus Acidithiobacillus has been widely used in bioleaching, and novel strains in this genus, such as A. ferriphilus, have also been confirmed to possess bioleaching capabilities. In this study, an Acidithiobacillus ferriphilus strain, QBS3, was isolated from zinc-rich sulfide mine drainage using the gradient dilution method. QBS3 is a Gram-negative, 1.3 µm rod-shaped bacterium with small red colonies. It showed a high iron oxidation efficiency of 0.361 g/(L·h) and a sulfur oxidation efficiency of 0.206 g/(L·d). QBS3 has sphalerite bioleaching ability; using QBS3 for pure sphalerite bioleaching, 18.8% of zinc was extracted in 14 days at 1% pulp density. Whole genome sequencing was performed on QBS3. Functional prediction showed that 9.13% of the genes were involved in replication, recombination, and repair. Bioleaching-related genes were analyzed, including iron and sulfur oxidation genes, and carbon and nitrogen fixation genes. For iron oxidation, the Cyc2→RusA pathway and Iro→RusB pathway were found in QBS3. In terms of sulfur oxidation, QBS3 has an incomplete SOX system and lacks the SDO gene, but Rho and Trx may complement the SOX system, enabling QBS3 to oxidize sulfur. QBS3 has multiple sets of carbon fixation genes, and nitrogen fixation genes were also identified. A hypothetical sphalerite bioleaching model is proposed; this study provides a theoretical basis for the zinc sulfide ore bioleaching industry. Full article
Show Figures

Figure 1

11 pages, 2051 KiB  
Article
Identification and Validation of Th1-Selective Epitopes Derived from Proteins Overexpressed in Breast Cancer Stem Cells
by Denise L. Cecil, Daniel Herendeen, Meredith Slota, Megan M. O’Meara, Yushe Dang, Lauren Corulli and Mary L. Disis
Vaccines 2025, 13(5), 525; https://doi.org/10.3390/vaccines13050525 - 15 May 2025
Viewed by 667
Abstract
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a [...] Read more.
Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a promising therapeutic approach. Methods: Twelve candidate CSC/EMT-associated proteins were identified through a systematic literature review. Human serum samples were assessed for antigen-specific IgG using ELISA. Th1/Th2 cytokine profiles, in response to predicted MHC II epitopes, were measured by ELISPOT in PBMCs. Epitope immunogenicity and tumor inhibition were evaluated in murine models, using either TNBC or luminal B syngeneic breast cancer cell lines. Results: Six of the candidate proteins (SOX2, YB1, FOXQ1, MDM2, CDH3, CD105) elicited antigen-specific IgG in human serum. Th1-selective epitopes, defined by high Th1/Th2 ratios, were identified for five of these proteins. Immunization of mice with peptide pools derived from CD105, CDH3, MDM2, SOX2, and YB1 induced significant antigen-specific IFN-γ responses. Tumor growth was significantly inhibited in the vaccinated mice across both the TNBC and luminal B breast cancer models, with mean tumor volume reductions ranging from 61% to 70%. Conclusions: CSC/EMT-associated antigens are immunogenic in humans and can be targeted using Th1-selective epitope-based vaccines. Immunization with these epitopes effectively inhibits tumor growth in multiple murine models of breast cancer. These findings support further clinical evaluation of CSC/EMT-targeted vaccines, especially for high-risk or advanced-stage breast cancer patients. Full article
Show Figures

Figure 1

17 pages, 10504 KiB  
Article
Construction and Influence of Induced Pluripotent Stem Cells on Early Embryo Development in Black Bone Sheep
by Daqing Wang, Yiyi Liu, Lu Li, Xin Li, Xin Cheng, Zhihui Guo, Guifang Cao and Yong Zhang
Biology 2025, 14(5), 484; https://doi.org/10.3390/biology14050484 - 28 Apr 2025
Viewed by 617
Abstract
The piggyBac+TET-on transposon induction system has a high efficiency in integrating exogenous genes in multiple cell types, can precisely integrate to reduce genomic damage, has a flexible gene expression regulation, and a strong genetic stability. When used in conjunction with somatic cell nuclear [...] Read more.
The piggyBac+TET-on transposon induction system has a high efficiency in integrating exogenous genes in multiple cell types, can precisely integrate to reduce genomic damage, has a flexible gene expression regulation, and a strong genetic stability. When used in conjunction with somatic cell nuclear transfer experiments, it can precisely and effectively reveal the intrinsic mechanisms of early biological development. This study successfully reprogrammed black-boned sheep fibroblasts (SFs) into induced pluripotent stem cells (iPSCs) using the piggyBac+TET-on transposon system and investigated their impact on early embryonic development. Seven exogenous reprogramming factors (bovine OCT4, SOX2, KLF4, cMyc, porcine NANOG, Lin-28, and SV40 Large T) were delivered into SFs, successfully inducing iPSCs. A growth performance analysis revealed that iPSC clones exhibited a raised or flat morphology with clear edges, positive alkaline phosphatase staining, and normal karyotypes. The transcriptome analysis indicated a significant enrichment of iPSCs in oxidative phosphorylation and cell proliferation pathways, with an up-regulated expression of the ATP5B, SDHB, Bcl-2, CDK1, and Cyclin D1 genes and a down-regulated expression of BAX (p < 0.05). Somatic cell nuclear transfer experiments demonstrated that the cleavage rate (85% ± 2.12) and blastocyst rate (52% ± 2.11) of the iPSCs were significantly higher than those of the SFs (p < 0.05). The detection of trilineage marker genes confirmed that the expression levels of endoderm (DCN, NANOS3, FOXA2, FOXD3, SOX17), mesoderm (KDR, CD34, NFH), and ectoderm (NEUROD) markers in iPSCs were significantly higher than in SFs (p < 0.01). The findings demonstrate that black-boned sheep iPSCs possess pluripotency and the potential to differentiate into all three germ layers, revealing the mechanisms by which reprogrammed iPSCs influence early embryonic development and providing a critical foundation for research on sheep pluripotent stem cells. Full article
Show Figures

Figure 1

26 pages, 4125 KiB  
Article
Adult B-Cell Acute Lymphoblastic Leukaemia Antigens and Enriched Pathways Identify New Targets for Therapy
by Eithar Mohamed, Sara Goodman, Leah Cooksey, Daniel M. Fletcher, Olivia Dean, Viktoriya B. Boncheva, Ken I. Mills, Kim H. Orchard and Barbara-ann Guinn
Onco 2025, 5(2), 19; https://doi.org/10.3390/onco5020019 - 22 Apr 2025
Viewed by 1546
Abstract
Background: Adult B-cell acute lymphoblastic leukaemia (aB-ALL) is characterised by abnormal differentiation and proliferation of lymphoid progenitors. Despite a significant improvement in relapse-free and overall survival for children with B-ALL, aB-ALL has a particularly poor prognosis with a 5-year survival rate of 20%. [...] Read more.
Background: Adult B-cell acute lymphoblastic leukaemia (aB-ALL) is characterised by abnormal differentiation and proliferation of lymphoid progenitors. Despite a significant improvement in relapse-free and overall survival for children with B-ALL, aB-ALL has a particularly poor prognosis with a 5-year survival rate of 20%. First remission is achieved for most patients, but relapse is common with a high associated mortality. New treatments such as immunotherapy offer an opportunity to extend remission and prevent relapse. Methods: aB-ALL antigens were identified using different sources—immunoscreening, protoarrays, two microarrays and one cancer-testis antigen database, and a review of the genomic analyses of aB-ALL. A total of 385 aB-ALL-associated gene products were examined for their association with patient survival. Results: We identified 87 transcripts with differential expression between aB-ALL and healthy volunteers (peripheral blood, bone marrow and purified CD19+ cells), and 42 that were associated with survival. Enrichr analysis showed that the Transforming Growth Factor-β (TGFβ), Wnt and Hippo pathways were highly represented (p < 0.02). We found that SOX4 and ROCK1 were upregulated in all types of B-ALL (ROCK1 having a p < 0.001 except in t(8;14) patients), as well as SMAD3 and TEAD4 upregulation being associated with survival (p = 0.0008, 0.05 and 0.001, respectively). Expression of each aB-ALL antigen was verified by qPCR, but only TEAD4 showed significant transcript upregulation in aB-ALL compared to healthy volunteer CD19+ cells (p = 0.01). Conclusions: We have identified a number of antigens and their pathways that play key roles in aB-ALL and may act as useful targets for future immunotherapy strategies. Full article
Show Figures

Figure 1

16 pages, 3702 KiB  
Article
γ-Aminobutyric Acid Transporter Mutation GAT1 (S295L) Substantially Impairs Neurogenesis in Dentate Gyrus
by Weitong Liu, Yantian Yang, Yichen Liu, Bingyan Ni, Hua Zhuang, Kexin Chen, Jiahao Shi, Chenxin Zhu, Haoyue Wang and Jian Fei
Brain Sci. 2025, 15(4), 393; https://doi.org/10.3390/brainsci15040393 - 13 Apr 2025
Viewed by 671
Abstract
Background: GABAergic signaling plays a crucial role in modulating neuronal proliferation, migration, and the formation of neural network connections. The termination of GABA transmission primarily occurs through the action of GABA transporter 1 (GAT1), encoded by the SLC6A1 gene. Multiple SLC6A1 mutations [...] Read more.
Background: GABAergic signaling plays a crucial role in modulating neuronal proliferation, migration, and the formation of neural network connections. The termination of GABA transmission primarily occurs through the action of GABA transporter 1 (GAT1), encoded by the SLC6A1 gene. Multiple SLC6A1 mutations have been implicated in neurodevelopmental disorders, but their effects on the nervous system are unclear. Methods: We estimated the expression pattern of the GAT1 (S295L) protein using the Slc6a1S295L/S295L mouse model via RT-PCR, Western blotting, and confocal immunofluorescence. The effect of GAT1 (S295L) on hippocampal neurogenesis was investigated by neuronal marker staining (Sox2, Tbr2, NeuroD1, DCX, NeuN) and BrdU label experiments. The dendritic complexity was mapped through Sholl analysis. RNA-Seq was utilized to explore the signaling pathways and molecules associated with neurodevelopmental disorders. Results: We detected a remarkable decline in the quantity of type-2b intermediate progenitor cells, neuroblasts, and immature neurons in the dentate gyrus (DG) of Slc6a1S295L/S295L mice at 4 weeks. These abnormalities were exacerbated in adulthood, as evidenced by compromised dendritic length and height as well as the complexity of immature neurons. Immunofluorescence staining showed the abnormal aggregation of GAT1 (S295L) protein in neurons. RNA-seq analysis identified pathways associated with neurodevelopment, neurological disorders, protein homeostasis, and neuronutrition. The neurotrophin Bdnf decreased at all ages in the Slc6a1S295L/S295L mice. Conclusions: Our data provide new evidence that GAT1 (S295L) causes impaired neurogenesis in the DG. GAT1 mutation not only disrupts GABA homeostasis but also impairs the neurotrophic support necessary for normal hippocampal development, which may be one of the factors contributing to impaired neurogenesis. Full article
(This article belongs to the Special Issue Molecular Genetics of Neurodevelopment Disorders)
Show Figures

Figure 1

Back to TopTop