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Keywords = intrinsic resistance (IRES)

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51 pages, 38711 KB  
Article
Design and Synthesis of Novel Morpholine-Derived Nitrogen-Rich Scaffolds as Multifunctional Anticancer and Antibacterial Agents: Biological Evaluation and Computational Studies
by Hagar S. El-Hema, Esraa Adel, Wagdy I. El-Dougdoug, Ashraf A. F. Wasfy, Ahmed F. El-Sayed, Eman S. Nossier, Modather F. Hussein, Reem Binsuwaidan, Asmaa Saleh and Adel A. -H. Abdel-Rahmanh
Pharmaceutics 2026, 18(8), 982; https://doi.org/10.3390/pharmaceutics18080982 - 9 Aug 2026
Viewed by 445
Abstract
Background/Objectives: The development of multifunctional small molecules capable of simultaneously addressing cancer progression and antimicrobial resistance represents an important challenge in medicinal chemistry. This study aimed to design, synthesize, and biologically evaluate a series of novel morpholine-based nitrogen-rich heterocyclic hybrids as potential anticancer [...] Read more.
Background/Objectives: The development of multifunctional small molecules capable of simultaneously addressing cancer progression and antimicrobial resistance represents an important challenge in medicinal chemistry. This study aimed to design, synthesize, and biologically evaluate a series of novel morpholine-based nitrogen-rich heterocyclic hybrids as potential anticancer and antibacterial agents, supported by computational investigations. Methods: Twelve morpholine-derived nitrogen-enriched heterocyclic hybrids incorporating pyran, triazine, pyrimidinone, and sulfur-containing scaffolds were synthesized and fully characterized using IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. Their antiproliferative activities were evaluated against MCF-7 and HCT-116 cancer cell lines. The most active compounds were further investigated through kinase inhibition assays, cell cycle analysis, apoptosis, mitochondrial membrane potential, intracellular ROS determination, and apoptosis-related gene expression. Antibacterial, antibiofilm, antioxidant, and computational studies, including molecular docking, molecular dynamics simulations, MM-GBSA/MM-PBSA binding free-energy calculations, DFT calculations, and ADMET prediction, were also performed. Results: Compounds 3, 10, and 12 exhibited the highest antiproliferative activity, with compound 10 emerging as the lead candidate. It potently inhibited EGFR, PI3K, and mTOR, with IC50 values of 0.086 ± 0.003, 0.107 ± 0.005, and 0.223 ± 0.008 μM, respectively. Mechanistic investigations revealed G2/M arrest in MCF-7 cells and G0/G1 arrest in HCT-116 cells, accompanied by apoptosis rates of 32.66% and 37.12%; mitochondrial membrane depolarization; a 3.55-fold increase in intracellular ROS; upregulation of caspase-3, caspase-9, and Bax; and downregulation of Bcl-2, supporting activation of the intrinsic apoptotic pathway. Compound 10 also displayed the broadest antibacterial spectrum, surpassed ciprofloxacin against several tested isolates, exhibited MIC values of 5–20 μg/mL, achieved 42.80% inhibition of Pseudomonas aeruginosa biofilm formation, and showed the strongest antioxidant activity in DPPH and ABTS assays. Computational analyses supported the experimental findings by predicting stable interactions with EGFR and Staphylococcus aureus DNA gyrase, together with favorable MM-GBSA/MM-PBSA binding free energies of −23.44 and −24.99 ± 2.71 kcal/mol, respectively. Conclusions: The present findings identify compound 10 as a promising multifunctional lead with potent anticancer, antibacterial, antibiofilm, antioxidant, and multitarget kinase inhibitory activities. The combined biochemical, cellular, and computational findings support the proposed involvement of the EGFR/PI3K/mTOR signaling pathway in its antiproliferative activity and identify DNA gyrase as a potential antibacterial target. Nevertheless, the present study is limited to in vitro biological evaluation and computational investigations. Therefore, further in vivo efficacy studies, pharmacokinetic profiling, toxicity assessment, and experimental validation of the proposed molecular targets are warranted before considering preclinical development. Full article
(This article belongs to the Section Drug Targeting and Design)
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26 pages, 2825 KB  
Review
The Benefits of Non-Pharmaceutic Interventions on Intrinsic Capacity in Insulin-Resistant Adult and Geriatric Populations—A Narrative Review
by Iulia-Daniela Lungu, Adina Carmen Ilie, Ramona Ștefăniu, Sabinne-Marie Albișteanu, Ana-Maria Turcu, Gabriela Grigoraș, Diana-Gabriela Constantinescu, Anca-Iuliana Pîslaru and Ioana Dana Alexa
J. Clin. Med. 2026, 15(15), 6101; https://doi.org/10.3390/jcm15156101 - 5 Aug 2026
Viewed by 303
Abstract
Insulin resistance (IR) is a well-established metabolic disorder characterized by reduced responsiveness of peripheral tissues to insulin, leading to hyperglycemia and compensatory hyperinsulinemia. Background: In older adults, IR tends to develop gradually and may remain undiagnosed for years due to the insidious [...] Read more.
Insulin resistance (IR) is a well-established metabolic disorder characterized by reduced responsiveness of peripheral tissues to insulin, leading to hyperglycemia and compensatory hyperinsulinemia. Background: In older adults, IR tends to develop gradually and may remain undiagnosed for years due to the insidious nature of the condition, which often lacks overt symptoms. Non-pharmacological interventions refer to the sum of all measures taken in order to improve a certain biological determination or physical parameter and they consist of lifestyle and dietary modifications. Although insulin resistance is recognized as a central mechanism involved in the development of numerous chronic diseases associated with aging, its impact on intrinsic capacity and the mechanisms underlying this relationship are insufficiently synthesized in the literature. In this context, the present narrative review aims to integrate the current evidence on the interaction between insulin resistance and intrinsic capacity, highlighting common biological mechanisms and potential therapeutic and preventive strategies to promote healthy aging. Methods: We conducted a literature search in PubMed, Scopus and Web of Science databases, screening the literature published between 2010 and January 2026. The search strategy included keywords and Boolean operators in order to refine the suggestions. Relevant articles, reviews, studies and guidelines were selected based on their relevance to the objective of this review. Results and Conclusions: The results of the review highlight that insulin resistance represents a central mechanism contributing to the decline in intrinsic capacity through chronic inflammation, oxidative stress, mitochondrial dysfunction and alteration of the gut microbiota. Current evidence suggests that nutritional interventions, in particular the Mediterranean diet and the DASH diet, can improve insulin sensitivity by modulating the microbiota and reducing systemic inflammation, with the potential to contribute to maintaining functional capacity and promoting healthy aging. Full article
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33 pages, 1151 KB  
Review
Mitochondria-Targeting Metal Complexes: Design Principles, Mechanisms of Action, and Translational Perspectives
by Donatella Coradduzza, Giacomo Senzacqua, Rosita Cappai and Serenella Medici
Biomolecules 2026, 16(7), 987; https://doi.org/10.3390/biom16070987 - 4 Jul 2026
Viewed by 513
Abstract
Mitochondria-targeting metal complexes (MTMCs) are a mechanistically distinct class of metallopharmaceuticals. Unlike first-generation platinum drugs that form nuclear DNA adducts, MTMCs exploit organelle-specific vulnerabilities such as hyperpolarised mitochondrial membrane potential (ΔΨm), elevated reactive oxygen species (ROS), limited mitochondrial DNA (mtDNA) repair capacity, and [...] Read more.
Mitochondria-targeting metal complexes (MTMCs) are a mechanistically distinct class of metallopharmaceuticals. Unlike first-generation platinum drugs that form nuclear DNA adducts, MTMCs exploit organelle-specific vulnerabilities such as hyperpolarised mitochondrial membrane potential (ΔΨm), elevated reactive oxygen species (ROS), limited mitochondrial DNA (mtDNA) repair capacity, and redox-dependent enzymes such as thioredoxin reductase (TrxR). We systematically searched PubMed, Web of Science, Scopus, and Google Scholar databases for studies published between 2016 and 2026, applying predefined inclusion criteria that included subcellular localization evidence and functional bioenergetic endpoints. The search identified 147 studies covering Pt(II/IV), Ru(II/III), Au(I/III), Ir(III), Os(II), Re(I), and V(IV/V) complexes and metal–organic framework nanoplatforms. Mechanistic evidence converges on four intramitochondrial target categories: inhibition of ETC (Electron Transport Chain) Complexes I/III with consequent ATP depletion; ROS overproduction, coupled with glutathione and TrxR depletion; outer mitochondrial membrane permeabilization and intrinsic apoptotic cascade activation; and mtDNA damage within a compartment limited to base excision repair. Multi-modal cell death—the co-occurrence of apoptosis, ferroptosis, necroptosis, and autophagic cell death—was a recurrent finding across the reviewed studies. This review thoroughly surveys the latest trends in MTMC drug design (metals, ligand structures, and mechanisms of action) and summarises analytical techniques for speciation, pharmacokinetics, safe monitoring, and resistance, while critically analysing translational barriers and clinical failures. To address the field’s inconsistent terminology, we introduce an explicit localization evidence hierarchy that distinguishes mitochondria-targeting complexes (through quantitative ICP-MS fractionation or co-localization with defined Pearson/Manders coefficients) from simply mitochondria-localising or mitochondria-perturbing agents, and we apply it throughout. We also point out that the idea of selectivity being purely driven by membrane voltage (ΔΨm) and thermodynamics is constrained by membrane and protein binding, as well as the transmembrane pH gradient, kinetic limitations, and demonstrated heterogeneity of cancer-cell membrane potential, and, as such, the functional mitochondrial effects must not be equated with mitochondrial accumulation. Since elemental quantification cannot distinguish intact complex from protein adducts and decomposition products, speciation-aware pharmacokinetics emerges as a prerequisite for a credible exposure–response interpretation. The translational progress will depend less on new chemotypes than on this analytical and pharmacokinetic rigour, together with organelle-level safety monitoring and biomarker-guided patient selection. Full article
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12 pages, 536 KB  
Article
Insulin Resistance and Metabolic Dysfunction in Early-Stage Parkinson’s Disease: Evidence from a Preliminary Case-Control Study
by Elena Contaldi, Lorenzo Ciocca, Francesco Mignone, Michela Barichella, Alessia Siribelli, Giulia Lazzeri, Ioannis Ugo Isaias, Gianni Pezzoli and Federica Invernizzi
J. Clin. Med. 2026, 15(3), 1021; https://doi.org/10.3390/jcm15031021 - 27 Jan 2026
Viewed by 996
Abstract
Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem disorder in which metabolic dysfunction may contribute to disease susceptibility and progression. Peripheral insulin resistance (IR) has been implicated in PD, but data in levodopa-naïve patients are currently limited. Objective: To investigate the [...] Read more.
Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem disorder in which metabolic dysfunction may contribute to disease susceptibility and progression. Peripheral insulin resistance (IR) has been implicated in PD, but data in levodopa-naïve patients are currently limited. Objective: To investigate the prevalence of IR and metabolic dysfunction in early-stage, levodopa-naïve PD patients and their association with clinical features. Methods: We conducted an exploratory case–control study including 20 levodopa-naïve PD patients and 40 age-, sex-, and BMI-matched healthy controls. Participants underwent comprehensive clinical and metabolic assessments, including fasting glucose, insulin, lipid profiles, and HOMA-IR calculation. Peripheral IR was defined using HOMA-IR cut-offs of ≥2.0 (primary analysis) and ≥2.5 (sensitivity analysis). ANCOVA adjusted for age, sex, and BMI was used for between-group comparisons. Results: PD patients exhibited higher fasting insulin (10.7 ± 5.2 vs. 8.0 ± 4.4 µIU/mL; p = 0.020) and HOMA-IR (2.63 ± 1.40 vs. 1.89 ± 1.21; p = 0.014) compared to controls. Using a HOMA-IR ≥ 2.0, IR prevalence was 70% in PD vs. 32.5% in controls (OR = 4.85, 95% CI 1.52–15.50, p = 0.012). ANCOVA analysis confirmed group differences after adjusting for covariates (respectively, p = 0.032 for insulin and p = 0.023 for HOMA-IR). A sensitivity analysis excluding six patients receiving dopaminergic therapy further supported the robustness of the results. No significant correlations were observed between IR and disease severity scores. Conclusions: Early-stage, levodopa-naïve PD patients exhibit a higher prevalence of peripheral insulin resistance compared with matched controls. These findings support the hypothesis that metabolic dysfunction is an intrinsic component of PD pathophysiology and may represent a target for early intervention. Full article
(This article belongs to the Special Issue Parkinson's Disease: Recent Advances in Diagnosis and Treatment)
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41 pages, 4627 KB  
Review
Research Progress in Chitin/Chitosan-Based Biomass Adhesives: Extraction Processes, Composite and Chemical Modification
by Yizhang Luo, Ziying Zhang, Jiachen Zuo and Libo Zhang
Polymers 2026, 18(3), 337; https://doi.org/10.3390/polym18030337 - 27 Jan 2026
Cited by 8 | Viewed by 2188
Abstract
Traditional fossil-based adhesives, hindered by issues such as formaldehyde emission, dependence on fossil resources, and poor biodegradability, struggle to meet the global demand for low-carbon green development. Biomass-based adhesives have thus emerged as a core alternative. Among them, chitin/chitosan derived from biomass waste [...] Read more.
Traditional fossil-based adhesives, hindered by issues such as formaldehyde emission, dependence on fossil resources, and poor biodegradability, struggle to meet the global demand for low-carbon green development. Biomass-based adhesives have thus emerged as a core alternative. Among them, chitin/chitosan derived from biomass waste such as shrimp and crab shells demonstrates significant potential in the adhesive field due to its renewability, controllable structure, biocompatibility, and inherent antibacterial properties. However, mainstream biomass adhesives like soy protein and starch adhesives suffer from poor water resistance and insufficient wet adhesion strength. Pure chitin/chitosan-based adhesive systems also exhibit low wet strength retention. Furthermore, the overall development faces challenges including high extraction costs, insufficient performance synergy, poor industrial compatibility, and a lack of standardized systems. This review follows the framework of “resource–extraction–modification–performance–application–challenges” to systematically summarize relevant research progress. It clarifies the molecular structure and intrinsic advantages of chitin/chitosan, outlines extraction processes such as acid/alkali and enzymatic methods, and characterization techniques including FT-IR and XRD. The review focuses on analyzing modification strategies such as composite modification, chemical modification, biomineralization, and biomimetic design, and verifies the application potential of these adhesives in wood processing, biomedicine, paper-based packaging, and other fields. Research indicates that chitin/chitosan-based adhesives provide an effective pathway for the green transformation of the adhesive industry. Future efforts should concentrate on developing green extraction processes, designing multifunctional integrated systems, and achieving full resource utilization of biomass. Additionally, establishing comprehensive standardized systems and promoting the translation of laboratory research into industrial applications are crucial to driving the industry’s green transition. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
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21 pages, 3438 KB  
Article
Physicochemical Properties of Biochar Produced from Grapevine-Pruning Residues of 12 Cultivars
by Danko Cvitan, Dominik Anđelini, Melissa Prelac, Qaiser Javed, Zoran Užila, Igor Pasković, Nikola Major, Marko Černe, Smiljana Goreta Ban, Marijan Bubola, Ana Jeromel, Tomislav Karažija, Marko Petek, Ivan Nemet and Igor Palčić
Horticulturae 2026, 12(1), 4; https://doi.org/10.3390/horticulturae12010004 - 19 Dec 2025
Cited by 3 | Viewed by 1594
Abstract
The valorization of grapevine pruning residues through pyrolysis provides a sustainable approach to agricultural waste management, producing biochar with agricultural use potential and carbon sink functionality. This study investigated pruning residues from 12 grapevine cultivars to evaluate the cultivar effects on biochar properties. [...] Read more.
The valorization of grapevine pruning residues through pyrolysis provides a sustainable approach to agricultural waste management, producing biochar with agricultural use potential and carbon sink functionality. This study investigated pruning residues from 12 grapevine cultivars to evaluate the cultivar effects on biochar properties. Samples were collected along the Croatian coast from Istria to Dalmatia and included six indigenous cultivars (Malvazija istarska, Pošip, Maraština, Teran, Plavina, and Plavac mali) and six introduced cultivars (Chardonnay, Pinot blanc, Sauvignon blanc, Merlot, Cabernet Sauvignon, and Syrah). For each cultivar, residues were collected from three distinct vineyards with three replicates per vineyard. Pyrolysis was conducted in a muffle furnace at 400 °C. The pruning residues showed acidic pH (4.79–5.45), moderate electrical conductivity (1694–2390 µS cm−1), and ash contents of 2.65–3.49% among all cultivars. Significant differences were observed among cultivars in residue carbon content and ash fraction, which were reflected in the resulting biochar. Biochar yield ranged from 32% to 35%, while pH values were alkaline, ranging from 10.20 to 11.13. Total carbon increased from 43.77 to 45.36% in grapevine-pruning residues to 65.88–71.57% in biochar. FT-IR spectra revealed cultivar-dependent variation in aromatic C=C intensification, while SEM analysis indicated differences in pore abundance and surface area (1.63–4.13 m2 g−1) between cultivars. These results demonstrate that carbon-dense cultivars produced biochars with greater structural stability, indicating enhanced resistance to decomposition. Spectroscopic and microscopic analyses consistently showed increased aromatic condensation, reduced aliphatic functionality, and greater porosity following pyrolysis. These cultivar-dependent differences highlight pruning residues as a chemically heterogeneous but predictable feedstock, with biochar properties primarily governed by the intrinsic characteristics of the source material. Full article
(This article belongs to the Special Issue Driving Sustainable Agriculture Through Scientific Innovation)
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16 pages, 1400 KB  
Review
Factors Contributing to Resistance to Ischemia-Reperfusion Injury in Olfactory Mitral Cells
by Choong-Hyun Lee, Ji Hyeon Ahn and Moo-Ho Won
Int. J. Mol. Sci. 2025, 26(11), 5079; https://doi.org/10.3390/ijms26115079 - 25 May 2025
Cited by 3 | Viewed by 2228
Abstract
Brain ischemia-reperfusion (IR) injury is a critical pathological process that leads to extensive neuronal death, with hippocampal pyramidal cells, particularly those in the cornu Ammonis 1 (CA1) subfield, being highly vulnerable. Until now, human olfactory mitral cell resistance to IR injury has not [...] Read more.
Brain ischemia-reperfusion (IR) injury is a critical pathological process that leads to extensive neuronal death, with hippocampal pyramidal cells, particularly those in the cornu Ammonis 1 (CA1) subfield, being highly vulnerable. Until now, human olfactory mitral cell resistance to IR injury has not been directly studied, but olfactory dysfunction in humans is frequently reported in systemic vascular conditions such as ischemic heart failure and may serve as an early clinical marker of neurological or cardiovascular disease. Mitral cells, the principal neurons of the olfactory bulb (OB), exhibit remarkable resistance to IR injury, suggesting the presence of unique molecular adaptations that support their survival under ischemic stress. Several factors may contribute to the resilience of mitral cells. They have a lower susceptibility to excitotoxicity, mitigating the harmful effects of excessive glutamate signaling. Additionally, they maintain efficient calcium homeostasis, preventing calcium overload—a major trigger for cell death in vulnerable neurons. Mitral cells may also express high baseline levels of antioxidant enzymes and their activities, counteracting oxidative stress. Their robust mitochondrial function enhances energy production and reduces susceptibility to metabolic failure. Furthermore, neuroprotective signaling pathways, including phosphatidylinositol-3-kinase (PI3K)/Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated antioxidative responses, further bolster their resistance. In addition to these intrinsic mechanisms, the unique microvascular architecture and metabolic support within the olfactory bulb provide an extra layer of protection. By comparing mitral cells to ischemia-sensitive neurons, key vulnerabilities—such as oxidative stress, excitotoxicity, calcium dysregulation, and mitochondrial dysfunction—can be identified and potentially mitigated in other brain regions. Understanding these molecular determinants of neuronal survival may offer valuable insights for developing novel neuroprotective strategies to combat IR injury in highly vulnerable areas, such as the hippocampus and cortex. Full article
(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion: 2nd Edition)
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22 pages, 3004 KB  
Article
Defective Intracellular Insulin/IGF-1 Signaling Elucidates the Link Between Metabolic Defect and Autoimmunity in Vitiligo
by Silvia Caputo, Federica Papaccio, Ramona Marrapodi, Gianluca Lopez, Paolo Iacovelli, Alessia Pacifico, Emilia Migliano, Carlo Cota, Anna Di Nardo, Mauro Picardo and Barbara Bellei
Cells 2025, 14(8), 565; https://doi.org/10.3390/cells14080565 - 9 Apr 2025
Cited by 6 | Viewed by 2515
Abstract
Background: Vitiligo is featured by the manifestation of white maculae and primarily results from inflammatory/immune-selective aggression to melanocytes. The trigger mechanism leading to the activation of resident immune cells in the skin still lacks a molecular description. There is growing evidence linking altered [...] Read more.
Background: Vitiligo is featured by the manifestation of white maculae and primarily results from inflammatory/immune-selective aggression to melanocytes. The trigger mechanism leading to the activation of resident immune cells in the skin still lacks a molecular description. There is growing evidence linking altered mitochondrial metabolism to vitiligo, suggesting that an underlying metabolic defect may enable a direct activation of the immune system. Recent evidence demonstrated the association of vitiligo with disorders related to systemic metabolism, including insulin resistance (IR) and lipid disarrangements. However, IR, defined as a cellular defect in the insulin-mediated control of glucose metabolism, and its possible role in vitiligo pathogenesis has not been proven yet. Methods: In this study, we compared the Ins/IGF-1 intracellular signaling of dermal and epidermal cells isolated from non-lesional vitiligo skin to that belonging to cells obtained from healthy donors. Results: We demonstrated that due to the intensified glucose uptake, S6, and insulin receptor substrate 1 (IRS1) chronic phosphorylation, their inducibilities were downsized, a condition that coincides with the definition of insulin resistance at the cellular level. Correspondingly, the mitogenic and metabolic activities normally provoked by Ins/IGF-1 exposure resulted in significantly compromised vitiligo cells (p ≤ 0.05). Besides all the vitiligo-derived skin cells manifesting an energetic disequilibrium consisting of a low ATP, catabolic processes activation, and chronic oxidative stress, the functional consequences of this state appear amplified in the keratinocyte lineage. Conclusion: The presented data argue for insulin and IGF-1 resistance collocating dysfunctional glucose metabolism in the mechanisms of vitiligo pathogenesis. In vitiligo keratinocytes, the intrinsic impairment of intracellular metabolic activities, particularly when associated with stimulation with Ins/IGF-1, converges into an aberrant pro-inflammatory phenotype that may initiate immune cell recruitment. Full article
(This article belongs to the Section Cellular Metabolism)
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18 pages, 1542 KB  
Article
Impacts of Epihomobrassinolide and Thiamethoxam·Flutolanil·Azoxystrobin on the Continuous Cropping Stress of Pinellia ternata
by Bing Tian, Chenglin Tang, Jiaqi Liu, Qiuping Wang, Wenhao Feng, Yue Su, Cheng Zhang and Yang Lei
Horticulturae 2024, 10(7), 696; https://doi.org/10.3390/horticulturae10070696 - 1 Jul 2024
Cited by 6 | Viewed by 1470
Abstract
Continuous cropping (CC) stress severely limits the growth and industrial development of Pinellia ternata. Epihomobrassinolide (EBR) is a natural product that widely participates in many the physiological activities of many plants. Thiamethoxam·flutolanil·azoxystrobin (TFA) has been registered as a seed coating agent in [...] Read more.
Continuous cropping (CC) stress severely limits the growth and industrial development of Pinellia ternata. Epihomobrassinolide (EBR) is a natural product that widely participates in many the physiological activities of many plants. Thiamethoxam·flutolanil·azoxystrobin (TFA) has been registered as a seed coating agent in crop production. In this work, the effects of seeds soaked with EBR, seeds coated with TFA, and their co-application on the plant growth, electrophysiological information (as physiological activities related to plant electrical signals), leaf photosynthesis, plant resistance, bulb quality, and yield of CC P. ternata were evaluated. The aim of this work is to excogitate a practicable agronomic measure for ameliorating the growth of CC P. ternata. The results show that soaking the seeds with EBR or coating the seeds with TFA could effectively enhance the plant height, leaf area, and stem diameter of CC P. ternata, promote its emergence seedling ratio, and decrease its inverted seedling ratio, and their associated application was found to be more efficient. Additionally, their associated application effectively enhanced the intrinsic capacitance (IC), intracellular water metabolism, nutrient transport, and metabolic activity and decreased the intrinsic resistance (IR), impedance (IZ), capacitive reactance (IXc), and inductive reactance (IXL). Meanwhile, their associated application could reliably enhance the photosynthetic capacity and stress resistance, and effectively improve the bulb quality and yield. This study emphasizes that the associated application of seeds soaked with a 0.004% aqueous EBR solution diluted 1000 times and seeds coated with a 24% TFA flowable concentrate at 1.6 mL kg−1 seed can be used as a novel and practicable technology for alleviating the CC stress of P. ternata and ameliorating its growth, electrophysiological information, resistance, quality, and yield. Full article
(This article belongs to the Section Biotic and Abiotic Stress)
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23 pages, 2264 KB  
Article
A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy
by Karen Gambaro, Maud Marques, Suzan McNamara, Mathilde Couetoux du Tertre, Cyrla Hoffert, Archana Srivastava, Anna Schab, Thierry Alcindor, Adrian Langleben, Lucas Sideris, Mahmoud Abdelsalam, Mustapha Tehfe, Felix Couture, Gerald Batist and Petr Kavan
Int. J. Mol. Sci. 2024, 25(1), 43; https://doi.org/10.3390/ijms25010043 - 19 Dec 2023
Cited by 2 | Viewed by 3756
Abstract
Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of [...] Read more.
Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients’ responses to regorafenib treatment. Full article
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30 pages, 7860 KB  
Article
Elaboration of Nanostructured Levan-Based Colloid System as a Biological Alternative with Antimicrobial Activity for Applications in the Management of Pathogenic Microorganisms
by Vitalijs Radenkovs, Anda Valdovska, Daiga Galina, Stefan Cairns, Dmitrijs Jakovlevs, Sergejs Gaidukovs, Ingmars Cinkmanis and Karina Juhnevica-Radenkova
Nanomaterials 2023, 13(22), 2969; https://doi.org/10.3390/nano13222969 - 17 Nov 2023
Cited by 10 | Viewed by 3297
Abstract
Considering the documented health benefits of bacterial exopolysaccharides (EPSs), specifically of bacterial levan (BL), including its intrinsic antimicrobial activity against certain pathogenic species, the current study concentrated on the development of active pharmaceutical ingredients (APIs) in the form of colloid systems (CoSs) containing [...] Read more.
Considering the documented health benefits of bacterial exopolysaccharides (EPSs), specifically of bacterial levan (BL), including its intrinsic antimicrobial activity against certain pathogenic species, the current study concentrated on the development of active pharmaceutical ingredients (APIs) in the form of colloid systems (CoSs) containing silver nanoparticles (AgNPs) employing in-house biosynthesized BL as a reducing and capping agent. The established protocol of fermentation conditions implicating two species of lactic acid bacteria (LAB), i.e., Streptococcus salivarius K12 and Leuconostoc mesenteroides DSM 20343, ensured a yield of up to 25.7 and 13.7 g L−1 of BL within 72 h, respectively. An analytical approach accomplished by Fourier-transform infrared (FT-IR) spectroscopy allowed for the verification of structural features attributed to biosynthesized BL. Furthermore, scanning electron microscopy (SEM) revealed the crystalline morphology of biosynthesized BL with a smooth and glossy surface and highly porous structure. Molecular weight (Mw) estimated by multi-detector size-exclusion chromatography (SEC) indicated that BL biosynthesized using S. salivarius K12 has an impressively high Mw, corresponding to 15.435 × 104 kilodaltons (kDa). In turn, BL isolated from L. mesenteroides DSM 20343 was found to have an Mw of only 26.6 kDa. Polydispersity index estimation (PD = Mw/Mn) of produced BL displayed a monodispersed molecule isolated from S. salivarius K12, corresponding to 1.08, while this was 2.17 for L. mesenteroides DSM 20343 isolate. The presence of fructose as the main backbone and, to a lesser extent, glucose and galactose as side chain molecules in EPS hydrolysates was supported by HPLC-RID detection. In producing CoS-BL@AgNPs within green biosynthesis, the presence of nanostructured objects with a size distribution from 12.67 ± 5.56 nm to 46.97 ± 20.23 was confirmed by SEM and energy-dispersive X-ray spectroscopy (EDX). The prominent inhibitory potency of elaborated CoS-BL@AgNPs against both reference test cultures, i.e., Pseudomonas aeruginosa, Escherichia coli, Enterobacter aerogenes, and Staphylococcus aureus and those of clinical origin with multi-drug resistance (MDR), was confirmed by disc and well diffusion tests and supported by the values of the minimum inhibitory and bactericidal concentrations. CoS-BL@AgNPs can be treated as APIs suitable for designing new antimicrobial agents and modifying therapies in controlling MDR pathogens. Full article
(This article belongs to the Special Issue Advances in Nanomedicine Biotechnologies)
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14 pages, 2483 KB  
Article
Appropriate Sodium Bicarbonate Concentration Enhances the Intracellular Water Metabolism, Nutrient Transport and Photosynthesis Capacities of Coix lacryma-jobi L.
by Haitao Li, Jiamei Lv, Yue Su and Yanyou Wu
Agronomy 2023, 13(7), 1790; https://doi.org/10.3390/agronomy13071790 - 3 Jul 2023
Cited by 18 | Viewed by 11576
Abstract
Karst ecological stresses are harmful to plant growth, especially high bicarbonate concentrations, drought, high pH, etc. In this study, the effects of 0, 2.0, 7.0 and 12.0 mmol L−1 sodium bicarbonate concentrations on the biomass, electrophysiological properties, intracellular water metabolism, nutrient transport, [...] Read more.
Karst ecological stresses are harmful to plant growth, especially high bicarbonate concentrations, drought, high pH, etc. In this study, the effects of 0, 2.0, 7.0 and 12.0 mmol L−1 sodium bicarbonate concentrations on the biomass, electrophysiological properties, intracellular water metabolism, nutrient transport, photosynthesis and chlorophyll fluorescence of Coix lacryma-jobi L. were investigated. The results show that 2.0 mmol L−1 sodium bicarbonate effectively improved the biomass formation of Coix lacryma-jobi L., notably increased its intrinsic capacitance (IC) and decreased its intrinsic resistance (IR), intrinsic impedance (IZ), intrinsic capacitive reactance (IXc) and intrinsic inductive reactance (IXL) as well as reliably enhanced its intracellular water metabolism, nutrient transport and photosynthetic capacities. However, 7.0 and 12.0 mmol L−1 sodium bicarbonate concentrations exhibited marked inhibitory effects on the plants’ photosynthetic rate, stomatal conductance, transpiration rate and dry weight, whereas they did not significantly change the intracellular water metabolism or the nutrient transport capacity of Coix lacryma-jobi L. This study highlights that appropriate bicarbonate levels could enhance the intracellular water metabolism, nutrient transport, photosynthesis and growth of Coix lacryma-jobi L., which can be rapidly monitored by the plant’s electrophysiological properties. Importantly, plant electrophysiological measurement is significantly superior to photosynthesis measurement. In the future, plant electrophysiological measurement can be used as a means to quickly and effectively evaluate the physiological response of plants to the external environment. Full article
(This article belongs to the Special Issue Emerging Research on Adaptive Plants in Karst Ecosystems)
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10 pages, 3635 KB  
Article
Increasing Electrical Resistivity of P-Type BiFeO3 Ceramics by Hydrogen Peroxide-Assisted Hydrothermal Synthesis
by Cristian Casut, Raul Bucur, Daniel Ursu, Iosif Malaescu and Marinela Miclau
Materials 2023, 16(8), 3130; https://doi.org/10.3390/ma16083130 - 16 Apr 2023
Cited by 1 | Viewed by 2571
Abstract
Bismuth ferrite (BiFeO3, BFO) is still widely investigated both because of the great diversity of its possible applications and from the perspective of intrinsic defect engineering in the perovskite structure. Defect control in BiFeO3 semiconductors could provide a key technology [...] Read more.
Bismuth ferrite (BiFeO3, BFO) is still widely investigated both because of the great diversity of its possible applications and from the perspective of intrinsic defect engineering in the perovskite structure. Defect control in BiFeO3 semiconductors could provide a key technology for overcoming undesirable limitations, namely, a strong leakage current, which is attributed to the presence of oxygen vacancies (VO) and Bi vacancies (VBi). Our study proposes a hydrothermal method for the reduction of the concentration of VBi during the ceramic synthesis of BiFeO3.Using hydrogen peroxide (H2O2) as part of the medium, p-type BiFeO3 ceramics characterized by their low conductivity were obtained. Hydrogen peroxide acted as the electron donor in the perovskite structure, controlling VBi in the BiFeO3 semiconductor, which caused the dielectric constant and loss to decrease along with the electrical resistivity. The reduction of Bi vacancies highlighted by a FT-IR and Mott—Schottky analysis has an expected contribution to the dielectric characteristic. A decrease in the dielectric constant (with approximately 40%) and loss (3 times) and an increase of the electrical resistivity (by 3 times) was achieved by the hydrogen peroxide-assisted hydrothermal synthesized BFO ceramics, as compared with the hydrothermal synthesized BFOs. Full article
(This article belongs to the Special Issue Elaboration of New Materials Using Hydrothermal Methods)
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20 pages, 3855 KB  
Article
Modulation of the Cytotoxic Properties of Pd(II) Complexes Based on Functionalized Carboxamides Featuring Labile Phosphoryl Coordination Sites
by Diana V. Aleksanyan, Aleksandr V. Konovalov, Svetlana G. Churusova, Ekaterina Yu. Rybalkina, Alexander S. Peregudov, Svetlana A. Aksenova, Evgenii I. Gutsul, Zinaida S. Klemenkova and Vladimir A. Kozlov
Pharmaceutics 2023, 15(4), 1088; https://doi.org/10.3390/pharmaceutics15041088 - 28 Mar 2023
Cited by 11 | Viewed by 3142
Abstract
Platinum-based drugs are commonly recognized as a keystone in modern cancer chemotherapy. However, intrinsic and acquired resistance as well as serious side effects often caused by the traditional Pt(II) anticancer agents prompt a continuous search for more selective and efficient alternatives. Today, significant [...] Read more.
Platinum-based drugs are commonly recognized as a keystone in modern cancer chemotherapy. However, intrinsic and acquired resistance as well as serious side effects often caused by the traditional Pt(II) anticancer agents prompt a continuous search for more selective and efficient alternatives. Today, significant attention is paid to the compounds of other transition metals, in particular those of palladium. Recently, our research group has suggested functionalized carboxamides as a useful platform for the creation of cytotoxic Pd(II) pincer complexes. In this work, a robust picolinyl- or quinoline-carboxamide core was combined with a phosphoryl ancillary donor group to achieve hemilabile coordination capable of providing the required level of thermodynamic stability and kinetic lability of the ensuing Pd(II) complexes. Several cyclopalladated derivatives featuring either a bi- or tridentate pincer-type coordination mode of the deprotonated phosphoryl-functionalized amides were selectively synthesized and fully characterized using IR and NMR spectroscopy as well as X-ray crystallography. The preliminary evaluation of the anticancer potential of the resulting palladocycles revealed a strong dependence of their cytotoxic properties on the binding mode of the deprotonated amide ligands and demonstrated certain advantages of the pincer-type ligation. Full article
(This article belongs to the Special Issue Beyond the Platinum in Metal-Based Cancer Therapy, 2nd Edition)
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14 pages, 8685 KB  
Article
Influences of Ultrasonic Treatments on the Structure and Antioxidant Properties of Sugar Beet Pectin
by Yingjie Xu, Jian Zhang, Jinmeng He, Ting Liu and Xiaobing Guo
Foods 2023, 12(5), 1020; https://doi.org/10.3390/foods12051020 - 28 Feb 2023
Cited by 20 | Viewed by 3018
Abstract
The objective of this study was to explore the structural changes and oxidation resistance of ultrasonic degradation products of sugar beet pectin (SBP). The changes in the structures and antioxidant activity between SBP and its degradation products were compared. As the ultrasonic treatment [...] Read more.
The objective of this study was to explore the structural changes and oxidation resistance of ultrasonic degradation products of sugar beet pectin (SBP). The changes in the structures and antioxidant activity between SBP and its degradation products were compared. As the ultrasonic treatment time increased, the content of α-D-1,4-galacturonic acid (GalA) also increased, to 68.28%. In addition, the neutral sugar (NS) content, esterification degree (DE), particle size, intrinsic viscosity and viscosity-average molecular weight (MV) of the modified SBP decreased. Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were used to study the degradation of the SBP structure after ultrasonication. After ultrasonic treatment, the DPPH and ABTS free radical scavenging activities of the modified SBP reached 67.84% and 54.67% at the concentration of 4 mg/mL, respectively, and the thermal stability of modified SBP was also improved. All of the results indicate that the ultrasonic technology is an environmentally friendly, simple, and effective strategy to improve the antioxidant capacity of SBP. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
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