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18 pages, 932 KiB  
Article
Agronomic Performance of Newly Developed Elite Cowpea Mutant Lines in Eswatini
by Kwazi A. K. Mkhonta, Hussein Shimelis, Seltene Abady and Asande Ngidi
Agriculture 2025, 15(15), 1631; https://doi.org/10.3390/agriculture15151631 - 27 Jul 2025
Abstract
Cowpea (Vigna unguiculata [L.] Walp) is a vital food security crop in sub-Saharan Africa, including Eswatini. The productivity of the crop is low (<600 kg/ha) in the country due to a lack of improved, locally adapted, and farmer-preferred varieties with biotic and [...] Read more.
Cowpea (Vigna unguiculata [L.] Walp) is a vital food security crop in sub-Saharan Africa, including Eswatini. The productivity of the crop is low (<600 kg/ha) in the country due to a lack of improved, locally adapted, and farmer-preferred varieties with biotic and abiotic stress tolerance. The objective of the study was to assess the agronomic performance of newly developed elite cowpea mutants to select best-yielding and adapted pure lines for production and genetic improvement in Eswatini. A total of 30 cowpea genotypes, including 24 newly developed advanced mutant lines, their 3 founder parents and 3 local checks, were profiled for major agronomic traits in two selected sites (Lowveld Experiment and Malkerns Research Stations) using a 6 × 5 alpha lattice design with three replications. A combined analysis of variance revealed that the genotype x location interaction effects were significant (p < 0.05) for germination percentage (DG %), days to flowering (DTF), days to maturity (DMT), number of pods per plant (NPP), pod length (PDL), number of seeds per pod (NSP), hundred seed weight (HSW), and grain yield (GYD). Elite mutant genotypes, including NKL9P7, BRR4P11, SHR9P5, and NKL9P7-2 exhibited higher grain yields at 3158.8 kg/ha, 2651.6 kg/ha, 2627.5 kg/ha, and 2255.8 kg/ha in that order. The highest-yielding mutant, NKL9P7, produced 70%, 61%, and 54% more grain yield than the check varieties Mtilane, Black Eye, and Accession 792, respectively. Furthermore, the selected genotypes displayed promising yield components such as better PDL (varying from 13.1 to 26.3 cm), NPP (15.9 to 26.8), and NSP (9.8 to 16.2). Grain yield had significant positive correlations (p < 0.05) with DG %, NSP, and NPP. The principal component analysis (PCA) revealed that 81.5% of the total genotypic variation was attributable to the assessed quantitative traits. Principal component (PC) 1 accounted for 48.6%, while PC 2 and PC 3 contributed 18.9% and 14% of the overall variation, respectively. Key traits correlated with PC1 were NPP with a loading score of 0.91, NSP (0.83), PDL (0.73), GYD (0.68), HSW (0.58), DMT (−0.60), and DTF (−0.43) in a desirable direction. In conclusion, genotypes NKL9P7, BRR4P11, SHR9P5, NKL9P7-2, Bira, SHR3P4, and SHR2P7 were identified as complementary parents with relatively best yields and local adaptation, making them ideal selections for direct production or breeding. The following traits, NPP, NSP, PDL, GYD, and HSW, offered unique opportunities for genotype selection in the cowpea breeding program in Eswatini. Full article
(This article belongs to the Section Crop Genetics, Genomics and Breeding)
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18 pages, 889 KiB  
Article
Dynamic Leader Election and Model-Free Reinforcement Learning for Coordinated Voltage and Reactive Power Containment Control in Offshore Island AC Microgrids
by Xiaolu Ye, Zhanshan Wang, Qiufu Wang and Shuran Wang
J. Mar. Sci. Eng. 2025, 13(8), 1432; https://doi.org/10.3390/jmse13081432 - 27 Jul 2025
Abstract
Island microgrids are essential for the exploitation and utilization of offshore renewable energy resources. However, voltage regulation and accurate reactive power sharing remain significant technical challenges that need to be addressed. To tackle these issues, this paper proposes an algorithm that integrates a [...] Read more.
Island microgrids are essential for the exploitation and utilization of offshore renewable energy resources. However, voltage regulation and accurate reactive power sharing remain significant technical challenges that need to be addressed. To tackle these issues, this paper proposes an algorithm that integrates a dynamic leader election (DLE) mechanism and model-free reinforcement learning (RL). The algorithm aims to address the issue of fixed leaders restricting reactive power flow between buses during heavy load variations in island microgrids, while also overcoming the challenge of obtaining model parameters such as resistance and inductance in practical microgrids. First, we establish a voltage containment control and reactive power error model for island alternating current (AC) microgrids and construct a corresponding value function based on this error model. Second, a dynamic leader election algorithm is designed to address the issue of fixed leaders restricting reactive power flow between buses due to preset voltage limits under unknown or heavy load conditions. The algorithm adaptively selects leaders based on bus load, allowing the voltage limits to adjust accordingly and regulating reactive power flow. Then, to address the difficulty of accurately acquiring parameters such as resistance and inductance in microgrid lines, a model-free reinforcement learning method is introduced. This method relies on real-time measurements of voltage and reactive power data, without requiring specific model parameters. Ultimately, simulation experiments on offshore island microgrids are conducted to validate the effectiveness of the proposed algorithm. Full article
(This article belongs to the Section Ocean Engineering)
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16 pages, 3903 KiB  
Article
Identification of Salt Tolerance-Related NAC Genes in Wheat Roots Based on RNA-Seq and Association Analysis
by Lei Zhang, Aili Wei, Weiwei Wang, Xueqi Zhang, Zhiyong Zhao and Linyi Qiao
Plants 2025, 14(15), 2318; https://doi.org/10.3390/plants14152318 - 27 Jul 2025
Abstract
Excavating new salt tolerance genes and utilizing them to improve salt-tolerant wheat varieties is an effective way to utilize salinized soil. The NAC gene family plays an important role in plant response to salt stress. In this study, 446 NAC sequences were isolated [...] Read more.
Excavating new salt tolerance genes and utilizing them to improve salt-tolerant wheat varieties is an effective way to utilize salinized soil. The NAC gene family plays an important role in plant response to salt stress. In this study, 446 NAC sequences were isolated from the whole genome of common wheat and classified into 118 members based on subgenome homology, named TaNAC1 to TaNAC118. Transcriptome analysis of salt-tolerant wheat breeding line CH7034 roots revealed that 144 of the 446 TaNAC genes showed significant changes in expression levels at least two time points after NaCl treatment. These differentially expressed TaNACs were divided into four groups, and Group 4, containing the largest number of 78 genes, exhibited a successive upregulation trend after salt treatment. Single nucleotide polymorphisms (SNPs) of the TaNAC gene family in 114 wheat germplasms were retrieved from the public database and were subjected to further association analysis with the relative salt-injury rates (RSIRs) of six root phenotypes, and then 20 SNPs distributed on chromosomes 1B, 2B, 2D, 3B, 3D, 5B, 5D, and 7A were correlated with phenotypes involving salt tolerance (p < 0.0001). Combining the results of RT-qPCR and association analysis, we further selected three NAC genes from Group 4 as candidate genes that related to salt tolerance, including TaNAC26-D3.2, TaNAC33-B, and TaNAC40-B. Compared with the wild type, the roots of the tanac26-d3.2 mutant showed shorter length, less volume, and reduced biomass after being subjected to salt stress. Four SNPs of TaNAC26-D3.2 formed two haplotypes, Hap1 and Hap2, and germplasms with Hap2 exhibited better salt tolerance. Snp3, in exon 3 of TaNAC26-D3.2, causing a synonymous mutation, was developed into a Kompetitive Allele-Specific PCR marker, K3, to distinguish the two haplotypes, which can be further used for wheat germplasm screening or marker-assisted breeding. This study provides new genes and molecular markers for improvement of salt tolerance in wheat. Full article
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26 pages, 3811 KiB  
Article
Development and Validation of Multi-Locus GWAS-Based KASP Markers for Maize Ustilago maydis Resistance
by Tao Shen, Huawei Gao, Chao Wang, Yunxiao Zheng, Weibin Song, Peng Hou, Liying Zhu, Yongfeng Zhao, Wei Song and Jinjie Guo
Plants 2025, 14(15), 2315; https://doi.org/10.3390/plants14152315 - 26 Jul 2025
Viewed by 104
Abstract
Corn smut, caused by Ustilago maydis, significantly threatens maize production. This study evaluated 199 maize inbred lines at the seedling stage under greenhouse conditions for resistance to U. maydis, identifying 39 highly resistant lines. A genome-wide association study (GWAS) using the [...] Read more.
Corn smut, caused by Ustilago maydis, significantly threatens maize production. This study evaluated 199 maize inbred lines at the seedling stage under greenhouse conditions for resistance to U. maydis, identifying 39 highly resistant lines. A genome-wide association study (GWAS) using the mrMLM model detected 19 significant single-nucleotide polymorphism (SNP) loci. Based on a linkage disequilibrium (LD) decay distance of 260 kb, 226 candidate genes were identified. Utilizing the significant loci chr1_244281660 and chr5_220156746, two kompetitive allele-specific PCR (KASP) markers were successfully developed. A PCR-based sequence-specific oligonucleotide probe hybridization technique applied to the 199 experimental lines and 60 validation lines confirmed polymorphism for both markers, with selection efficiencies of 48.12% and 43.33%, respectively. The tested materials were derived from foundational inbred lines of domestic and foreign origin. Analysis of 39 highly resistant lines showed that the advantageous alleles carrying thymine/cytosine (T/C) predominated at frequencies of 94.87% and 53.84%, respectively. The genotype TTCC conferred high resistance, while CCTT was highly susceptible. The resistance exhibited high heritability and significant gene-by-environment interaction. This work systematically dissects the genetic basis of common smut resistance in maize, identifies favorable alleles, and provides a novel KASP marker-based strategy for developing disease-resistant germplasm. Full article
(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)
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21 pages, 861 KiB  
Review
Bispecific Antibodies and Antibody–Drug Conjugates in Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma, Focusing on Diffuse Large B-Cell Lymphoma
by Santino Caserta, Chiara Campo, Gabriella Cancemi, Santo Neri, Fabio Stagno, Donato Mannina and Alessandro Allegra
Cancers 2025, 17(15), 2479; https://doi.org/10.3390/cancers17152479 - 26 Jul 2025
Viewed by 88
Abstract
Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to [...] Read more.
Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody–drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody–drug conjugates. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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24 pages, 10103 KiB  
Article
Design Technique and Efficient Polyphase Implementation for 2D Elliptically Shaped FIR Filters
by Doru Florin Chiper and Radu Matei
Sensors 2025, 25(15), 4644; https://doi.org/10.3390/s25154644 - 26 Jul 2025
Viewed by 54
Abstract
This paper presents a novel analytical approach for the efficient design of a particular class of 2D FIR filters, having a frequency response with an elliptically shaped support in the frequency plane. The filter design is based on a Gaussian shaped prototype filter, [...] Read more.
This paper presents a novel analytical approach for the efficient design of a particular class of 2D FIR filters, having a frequency response with an elliptically shaped support in the frequency plane. The filter design is based on a Gaussian shaped prototype filter, which is frequently used in signal and image processing. In order to express the Gaussian prototype frequency response as a trigonometric polynomial, we developed it into a Fourier series up to a specified order, given by the imposed approximation precision. We determined analytically a 1D to 2D frequency transformation, which was applied to the factored frequency response of the prototype, yielding directly the factored frequency response of a directional, elliptically shaped 2D filter, with specified selectivity and an orientation angle. The designed filters have accurate shapes and negligible distortions. We also designed a 2D uniform filter bank of elliptical filters, which was then applied in decomposing a test image into sub-band images, thus proving its usefulness as an analysis filter bank. Then, the original image was accurately reconstructed from its sub-band images. Very selective directional elliptical filters can be used in efficiently extracting straight lines with specified orientations from images, as shown in simulation examples. A computationally efficient implementation at the system level was also discussed, based on a polyphase and block filtering approach. The proposed implementation is illustrated for a smaller size of the filter kernel and input image and is shown to have reduced computational complexity due to its parallel structure, being much more arithmetically efficient compared not only to the direct filtering approach but also with the most recent similar implementations. Full article
(This article belongs to the Section Sensing and Imaging)
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13 pages, 617 KiB  
Article
Management and Outcomes of Blunt Renal Trauma: A Retrospective Analysis from a High-Volume Urban Emergency Department
by Bruno Cirillo, Giulia Duranti, Roberto Cirocchi, Francesca Comotti, Martina Zambon, Paolo Sapienza, Matteo Matteucci, Andrea Mingoli, Sara Giovampietro and Gioia Brachini
J. Clin. Med. 2025, 14(15), 5288; https://doi.org/10.3390/jcm14155288 - 26 Jul 2025
Viewed by 67
Abstract
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are [...] Read more.
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are primarily dictated by hemodynamic stability, overall clinical condition, comorbidities, and injury severity graded according to the AAST classification. This study aimed to evaluate the effectiveness of non-operative management (NOM) in high-grade renal trauma (AAST grades III–V), beyond its established role in low-grade injuries (grades I–II). Secondary endpoints included the identification of independent prognostic factors for NOM failure and in-hospital mortality. Methods: We conducted a retrospective observational study including patients diagnosed with blunt renal trauma who presented to the Emergency Department of Policlinico Umberto I in Rome between 1 January 2013 and 30 April 2024. Collected data comprised demographics, trauma mechanism, vital signs, hemodynamic status (shock index), laboratory tests, blood gas analysis, hematuria, number of transfused RBC units in the first 24 h, AAST renal injury grade, ISS, associated injuries, treatment approach, hospital length of stay, and mortality. Statistical analyses, including multivariable logistic regression, were performed using SPSS v28.0. Results: A total of 244 patients were included. Low-grade injuries (AAST I–II) accounted for 43% (n = 105), while high-grade injuries (AAST III–V) represented 57% (n = 139). All patients with low-grade injuries were managed non-operatively. Among high-grade injuries, 124 patients (89%) were treated with NOM, including observation, angiography ± angioembolization, stenting, or nephrostomy. Only 15 patients (11%) required nephrectomy, primarily due to persistent hemodynamic instability. The overall mortality rate was 13.5% (33 patients) and was more closely associated with the overall injury burden than with renal injury severity. Multivariable analysis identified shock index and active bleeding on CT as independent predictors of NOM failure, whereas ISS and age were significant predictors of in-hospital mortality. Notably, AAST grade did not independently predict either outcome. Conclusions: In line with the current international literature, our study confirms that NOM is the treatment of choice not only for low-grade renal injuries but also for carefully selected hemodynamically stable patients with high-grade trauma. Our findings highlight the critical role of physiological parameters and overall ISS in guiding management decisions and underscore the need for individualized assessment to minimize unnecessary nephrectomies and optimize patient outcomes. Full article
(This article belongs to the Special Issue Emergency Surgery: Clinical Updates and New Perspectives)
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24 pages, 2603 KiB  
Article
Discrete Meta-Modeling Method of Breakable Corn Kernels with Multi-Particle Sub-Area Combinations
by Jiangdong Xu, Yanchun Yao, Yongkang Zhu, Chenxi Sun, Zhi Cao and Duanyang Geng
Agriculture 2025, 15(15), 1620; https://doi.org/10.3390/agriculture15151620 - 26 Jul 2025
Viewed by 62
Abstract
Simulation is an important technical tool in corn threshing operations, and the establishment of the corn kernel model is the core part of the simulation process. The existing modeling method is to treat the whole kernel as a rigid body, which cannot be [...] Read more.
Simulation is an important technical tool in corn threshing operations, and the establishment of the corn kernel model is the core part of the simulation process. The existing modeling method is to treat the whole kernel as a rigid body, which cannot be crushed during the simulation process, and the calculation of the crushing rate needs to be considered through multiple criteria such as the contact force, the number of collisions, and so on. Aiming at the issue that kernel crushing during maize threshing cannot be accurately modeled in discrete element simulations, in this study, a sub-area crushing model was constructed; representative samples with 26%, 30% and 34% moisture content were selected from a double-season maturing region in China; based on the physical dimensions and biological structure of the maize kernel, three stress regions were defined; and mechanical property tests were conducted on each of the three stress regions using a texturometer as a way to determine the different crushing forces due to the heterogeneity of the maize structure. The correctness of the model was verified by stacking angle and mechanical property experiments. A discrete element model of corn kernels was established using the Bonding V2 method and sub-area modeling. Bonding parameters were calculated by combining stacking angle tests and mechanical property tests. The flattened corn kernel was used as a prototype, and the bonding parameters were determined through size and mechanical property tests. A 22-ball bonding model was developed using dimensional parameters, and the kernel density was recalculated. Results showed that the relative error between the stacking angle test and the measured mean value was 0.31%. The maximum deviation of axial compression simulation results from the measured mean value was 22.8 N, and the minimum deviation was 3.67 N. The errors between simulated and actual rupture forces at the three force areas were 5%, 10%, and 0.6%, respectively. The decreasing trend of the maximum rupture force for the three moisture levels in the simulation matched that of the actual rupture force. The discrete element model can accurately reflect the rupture force, energy relationship, and rupture process on both sides, top, and bottom of the grain, and it can solve the error problem caused by the contact between the threshing element and the grain line in the actual threshing process to achieve the design optimization of the threshing drum. The modeling method provided in this study can also be applied to breakable discrete element models for wheat and soybean, and it provides a reference for optimizing the design of subsequent threshing devices. Full article
(This article belongs to the Section Agricultural Technology)
14 pages, 1203 KiB  
Article
Evaluation of the Kernel Test Weight and Selection of Identification Indexes of Maize Inbred Lines
by Tao Shen, Jianping Li, Chao Wang, Haihong Fan, Yunxiao Zheng, Yifan Liu, Shuzhen Zhang, Liying Zhu, Xiaoyan Jia, Yongfeng Zhao, Wei Song and Jinjie Guo
Agronomy 2025, 15(8), 1807; https://doi.org/10.3390/agronomy15081807 - 26 Jul 2025
Viewed by 56
Abstract
Kernel test weight (KTW) is one of the important assessment indexes of maize quality grade and one of the important influencing factors of yield. This study analyzed 12 traits related to KTW in 321 maize inbred lines using multivariate methods. The principal component [...] Read more.
Kernel test weight (KTW) is one of the important assessment indexes of maize quality grade and one of the important influencing factors of yield. This study analyzed 12 traits related to KTW in 321 maize inbred lines using multivariate methods. The principal component analysis (PCA) indicated that the four PCs covered 78.176% of the information of the 12 traits in 321 maize inbred lines. Cluster analysis categorized the maize lines into six groups, identifying 16 elite inbred lines with the highest KTW. A stepwise regression model for KWT evaluation was developed using four PCA traits: starch content, amylopectin content, 100-kernel weight, and kernel circumference. The findings of this study serve as a valuable reference point for the genetic improvement of maize germplasm re-sources in kernel test weight and the creation of high kernel test weight maize resources. Full article
(This article belongs to the Section Crop Breeding and Genetics)
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12 pages, 1243 KiB  
Article
The Pharmacological Evidences for the Involvement of AhR and GPR35 Receptors in Kynurenic Acid-Mediated Cytokine and Chemokine Secretion by THP-1-Derived Macrophages
by Katarzyna Sawa-Wejksza, Jolanta Parada-Turska and Waldemar Turski
Molecules 2025, 30(15), 3133; https://doi.org/10.3390/molecules30153133 - 26 Jul 2025
Viewed by 166
Abstract
Kynurenic acid (KYNA), a tryptophan metabolite, possesses immunomodulatory properties, although the molecular mechanism of this action has not yet been resolved. In the present study, the effects of KYNA on the secretion of selected cytokines and chemokines by macrophages derived from the human [...] Read more.
Kynurenic acid (KYNA), a tryptophan metabolite, possesses immunomodulatory properties, although the molecular mechanism of this action has not yet been resolved. In the present study, the effects of KYNA on the secretion of selected cytokines and chemokines by macrophages derived from the human THP-1 cell line are investigated. Furthermore, the involvement of the aryl hydrocarbon receptor (AhR) and the G protein-coupled receptor 35 (GPR35) in mediating the effects of KYNA was examined. In lipopolysaccharide (LPS)-stimulated THP-1-derived macrophages, KYNA significantly reduced IL-6 and CCL-2, but increased IL-10 and M-CSF levels. AhR antagonist CH-223191 reduced the KYNA influence on IL-6, CCL-2, and M-CSF production, while the GPR35 antagonist, ML-145, blocked KYNA-induced IL-10 production. Furthermore, it was shown that THP-1 derived macrophages were capable of synthesizing and releasing KYNA and that its production was increased in the presence of LPS. These findings suggest that THP-1-derived macrophages are a source of KYNA and that KYNA modulates inflammatory responses predominantly through AhR and GPR35 receptors. Our study provides further evidence for the involvement of macrophages in immunomodulatory processes that are dependent on AhR and GPR35 receptors, as well as the potential role of KYNA in these phenomena. Full article
(This article belongs to the Section Medicinal Chemistry)
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24 pages, 2279 KiB  
Article
Insights into the Structural Patterns in Human Glioblastoma Cell Line SF268 Activity and ADMET Prediction of Curcumin Derivatives
by Lorena Coronado, Johant Lakey-Beitia, Marisin Pecchio, Michelle G. Ng, Ricardo Correa, Gerardo Samudio-Ríos, Jessica Cruz-Mora, Arelys L. Fuentes, K. S. Jagannatha Rao and Carmenza Spadafora
Pharmaceutics 2025, 17(8), 968; https://doi.org/10.3390/pharmaceutics17080968 - 25 Jul 2025
Viewed by 195
Abstract
Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable [...] Read more.
Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: Twenty-one curcumin derivatives were assessed and subjected to in vitro MTT cytotoxicity assays in SF268 glioblastoma and Vero cells. On the basis of the cytotoxicity results, six derivatives with the most favorable characteristics were selected for additional mechanistic studies, which included microtubule depolymerization, mitochondrial membrane potential (ΔΨm), and BAX activation assays. ADMET properties were determined in silico. Results: Compounds 24, 6, and 11 demonstrated better activity (IC50: 0.59–3.97 µg/mL and SI: 3–20) than curcumin (IC50: 6.3 µg/mL; SI: 2.5). Lead derivatives destabilized microtubules, induced ΔΨm collapse, and activated BAX. In silico ADMET prediction analysis revealed that compounds 4 and 6 were the most promising for oral administration from a biopharmaceutical and pharmacokinetic point of view. Conclusions: Strategic modifications were made to one or both hydroxyl groups of the aromatic rings of curcumin to increase its physicochemical stability and activity against glioblastoma cell line SF268. Compound 4, bearing fully protected aromatic domains, was identified as a prime candidate for in vivo validation and formulation development. Full article
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17 pages, 440 KiB  
Review
Diagnosis and Management of Upper Tract Urothelial Carcinoma: A Review
by Domenique Escobar, Christopher Wang, Noah Suboc, Anishka D’Souza and Varsha Tulpule
Cancers 2025, 17(15), 2467; https://doi.org/10.3390/cancers17152467 - 25 Jul 2025
Viewed by 170
Abstract
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable [...] Read more.
Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article
(This article belongs to the Special Issue Upper Tract Urothelial Carcinoma: Current Knowledge and Perspectives)
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21 pages, 2352 KiB  
Article
Saponins from Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh: Comparative Assessment of Cytotoxic Potential Against a Wide Panel of Cancer Cell Lines
by Karolina Grabowska, Adam Mynarski, Agnieszka Galanty, Dagmara Wróbel-Biedrawa, Paweł Żmudzki and Irma Podolak
Molecules 2025, 30(15), 3126; https://doi.org/10.3390/molecules30153126 - 25 Jul 2025
Viewed by 81
Abstract
Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound 1), were isolated from the fruits of Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound 4) and a commercially available [...] Read more.
Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound 1), were isolated from the fruits of Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound 4) and a commercially available 28-O-β-D-glucopyranosyl hederagenin ester (compound 3), were evaluated for cytotoxicity and selectivity across a wide panel of human cancer cell lines (skin, prostate, gastrointestinal, thyroid, and lung). All four compounds exhibited dose- and time-dependent effects, with varying potency depending on the specific cancer type. The isolated bidesmosidic saponin (3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin 28-O-β-D-glucopyranosyl ester—compound 2) showed the strongest activity and selectivity, with an IC50 = 6.52 μg/mL after 48 h incubation against WM793 melanoma, and almost no effect on normal HaCaT skin cells (IC50 = 39.94 μg/mL). Multivariate analysis of the obtained data using principal component analysis (PCA) and hierarchical cluster analysis (HCA) supported the assumption that cytotoxicity is influenced by the type of compound, its concentration, and the intrinsic sensitivity of the cell line. Structure-activity observations between closely related hederagenin derivatives are also briefly presented. Full article
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23 pages, 2161 KiB  
Review
Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines
by Dyllan Rives, Tara Richbourg, Sierra Gurtler, Julia Martone and Mark A. Blenner
Int. J. Mol. Sci. 2025, 26(15), 7189; https://doi.org/10.3390/ijms26157189 - 25 Jul 2025
Viewed by 111
Abstract
Chinese hamster ovary (CHO) cells are the most common protein production platform for glycosylated biopharmaceuticals due to their relatively efficient secretion systems, post-translational modification (PTM) machinery, and quality control mechanisms. However, high productivity and titer demands can overburden these processes. In particular, the [...] Read more.
Chinese hamster ovary (CHO) cells are the most common protein production platform for glycosylated biopharmaceuticals due to their relatively efficient secretion systems, post-translational modification (PTM) machinery, and quality control mechanisms. However, high productivity and titer demands can overburden these processes. In particular, the endoplasmic reticulum (ER) can become overwhelmed with misfolded proteins, triggering the unfolded protein response (UPR) as evidence of ER stress. The UPR increases the expression of multiple genes/proteins, which are beneficial to protein folding and secretion. However, if the stressed ER cannot return to a state of homeostasis, a prolonged UPR results in apoptosis. Because ER stress poses a substantial bottleneck for secreting protein therapeutics, CHO cells are both selected for and engineered to improve high-quality protein production through optimized UPR and ER stress management. This is vital for optimizing industrial CHO cell fermentation. This review begins with an overview of common ER-stress related markers. Next, the optimal UPR profile of high-producing CHO cells is discussed followed by the context-dependency of a UPR profile for any given recombinant CHO cell line. Recent efforts to control and engineer ER stress-related responses in CHO cell lines through the use of various bioprocess operations and activation/inhibition strategies are elucidated. Finally, this review concludes with a discussion on future directions for engineering the CHO cell UPR. Full article
(This article belongs to the Special Issue New Insights into the Molecular Mechanisms of the UPR and Cell Stress)
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24 pages, 1222 KiB  
Article
Advancing Port Sustainability in the Baltic Sea Region: A Comparative Analysis Using the SMCC Framework
by Mari-Liis Tombak, Deniece Melissa Aiken, Eliise Toomeoja and Ulla Pirita Tapaninen
Sustainability 2025, 17(15), 6764; https://doi.org/10.3390/su17156764 - 25 Jul 2025
Viewed by 258
Abstract
Ports in the Baltic Sea region play an integral role in advancing sustainable maritime practices in the area, due to their geographic interconnectedness, economic importance, and sensitivity to environmental challenges. While numerous port sustainability assessment methods exist, most of which are grounded in [...] Read more.
Ports in the Baltic Sea region play an integral role in advancing sustainable maritime practices in the area, due to their geographic interconnectedness, economic importance, and sensitivity to environmental challenges. While numerous port sustainability assessment methods exist, most of which are grounded in the Triple Bottom Line (TBL) metric, many tend to emphasise whether specific targets have been met, rather than evaluating port sustainability on a scalar basis. This study explores the sustainability strategies of seven selected ports in five Baltic Sea countries using an innovative qualitative evaluation framework developed by the Swedish Maritime Competence Centre (SMCC). The SMCC model integrates the three core pillars of sustainability-environmental, social, and economic dimensions, while incorporating energy efficiency and digitalisation as critical enablers of modern port operations. The findings reveal significant variation in sustainability performance among the selected ports, shaped by regional contexts, operational profiles, and prior engagement with sustainability initiatives. Also, the results bring into light the most common sustainable practices used in the ports, e.g., LED lightning, onshore power supply, and port information systems. Full article
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