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17 pages, 7385 KiB  
Article
Microbial Alliance of Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 Enhances Nitrogen Fixation, Yield, and Salinity Tolerance in Black Gram Under Saline, Nutrient-Depleted Soils
by Praveen Kumar Tiwari, Anchal Kumar Srivastava, Rachana Singh and Alok Kumar Srivastava
Nitrogen 2025, 6(3), 66; https://doi.org/10.3390/nitrogen6030066 (registering DOI) - 7 Aug 2025
Abstract
Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus [...] Read more.
Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 on black gram performance under saline field conditions (EC: 8.87 dS m−1; pH: 8.37) with low organic carbon (0.6%) and nutrient deficiencies. In vitro assays demonstrated the biocontrol potential of SPR11, inhibiting Fusarium oxysporum and Macrophomina phaseolina by 76% and 62%, respectively. Germination assays and net house experiments under 300 mM NaCl stress showed that co-inoculation significantly improved physiological traits, including germination rate, root length (61.39%), shoot biomass (59.95%), and nitrogen fixation (52.4%) in nitrogen-free media. Field trials further revealed enhanced stress tolerance markers: chlorophyll content increased by 54.74%, proline by 50.89%, and antioxidant enzyme activities (SOD, CAT, PAL) were significantly upregulated. Electrolyte leakage was reduced by 55.77%, indicating improved membrane stability. Agronomic performance also improved, with co-inoculated plants showing increased root length (7.19%), grain yield (15.55 q ha−1; 77.04% over control), total biomass (26.73 q ha−1; 57.06%), and straw yield (8.18 q ha−1). Pod number, seed count, and seed weight were also enhanced. Nutrient analysis showed elevated uptake of nitrogen, phosphorus, potassium, and key micronutrients (Zn, Fe) in both grain and straw. To the best of our knowledge, this is the very first field-based report demonstrating the synergistic benefits of co-inoculating Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 in black gram under saline, nutrient-poor conditions without external nitrogen inputs. The results highlight a sustainable strategy to enhance legume productivity and resilience in salt-affected soils. Full article
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19 pages, 3275 KiB  
Article
Polysialylation of Glioblastoma Cells Is Regulated by Autophagy Under Nutrient Deprivation
by Sofia Scibetta, Giuseppe Pepe, Marco Iuliano, Alessia Iaiza, Elisabetta Palazzo, Marika Quadri, Thomas J. Boltje, Francesco Fazi, Vincenzo Petrozza, Sabrina Di Bartolomeo, Alba Di Pardo, Antonella Calogero, Giorgio Mangino, Vittorio Maglione and Paolo Rosa
Int. J. Mol. Sci. 2025, 26(15), 7625; https://doi.org/10.3390/ijms26157625 - 6 Aug 2025
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant [...] Read more.
Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article
(This article belongs to the Special Issue Targeting Glioblastoma Metabolism)
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20 pages, 7055 KiB  
Article
Cardiopulmonary Bypass-Induced IL-17A Aggravates Caspase-12-Dependent Neuronal Apoptosis Through the Act1-IRE1-JNK1 Pathway
by Ruixue Zhao, Yajun Ma, Shujuan Li and Junfa Li
Biomolecules 2025, 15(8), 1134; https://doi.org/10.3390/biom15081134 - 6 Aug 2025
Abstract
Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose [...] Read more.
Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery. Full article
(This article belongs to the Section Molecular Medicine)
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17 pages, 972 KiB  
Article
A Preliminary Investigation into Heavy Metal Tolerance in Pseudomonas Isolates: Does the Isolation Site Have an Effect?
by Alessandro De Santis, Antonio Bevilacqua, Angela Racioppo, Barbara Speranza, Maria Rosaria Corbo, Clelia Altieri and Milena Sinigaglia
Agriculture 2025, 15(15), 1692; https://doi.org/10.3390/agriculture15151692 - 5 Aug 2025
Abstract
One hundred presumptive Pseudomonas isolates, recovered from 15 sites impacted by anthropogenic activity in the Foggia district (Italy), were screened for key adaptive and functional traits important for environmental applications. The isolates were phenotypically characterized for their ability to grow under combined pH [...] Read more.
One hundred presumptive Pseudomonas isolates, recovered from 15 sites impacted by anthropogenic activity in the Foggia district (Italy), were screened for key adaptive and functional traits important for environmental applications. The isolates were phenotypically characterized for their ability to grow under combined pH (5.0–8.0) and temperature (15–37 °C) conditions, to produce proteolytic enzymes, pigments, and exopolysaccharides, and to tolerate SDS. Moreover, the resistance to six environmentally relevant heavy metals (Cd, Co, Cu, Ni, Zn, As) was qualitatively assessed. The results highlighted wide inter-strain variability, with distinct clusters of isolates showing unique combinations of stress tolerance, enzymatic potential, and resistance profile. PERMANOVA analysis revealed significant effects of both the isolation site and the metal type, as well as their interaction, on the observed resistance patterns. A subset of isolates showed co-tolerance to elevated temperatures and heavy metals. These findings offer an initial yet insightful overview of the adaptive diversity of soil-derived Pseudomonas, laying the groundwork for the rational selection of strains for bioaugmentation in contaminated soils. Full article
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18 pages, 1602 KiB  
Article
Interacting Effects of Heat and Nanoplastics Affect Wheat (Triticum turgidum L.) Seedling Growth and Physiology
by Debora Fontanini, Stefania Bottega, Monica Ruffini Castiglione and Carmelina Spanò
Plants 2025, 14(15), 2426; https://doi.org/10.3390/plants14152426 - 5 Aug 2025
Abstract
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that [...] Read more.
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that their interaction may exacerbate the effects observed under each stressor individually, we investigated the response of seedlings of Triticum turgidum to treatments with fluorescent polystyrene nanoplastics under optimal (25 °C) and elevated (35 °C) temperature conditions. We evaluated seedling growth, photosynthetic pigment content, and oxidative stress markers using both biochemical and histochemical techniques. In addition, we assessed enzymatic and non-enzymatic antioxidant responses. The use of fluorescently labeled nanoplastics enabled the visualization of their uptake and translocation within plant tissues. Elevated temperatures negatively affect plant growth, increasing the production of proline, a key protective molecule, and weakly activating secondary defense mechanisms. Nanoplastics disturbed wheat seedling physiology, with these effects being amplified under high temperature conditions. Combined stress enhances nanoplastic uptake in roots, increases oxidative damage, and alters antioxidant responses, reducing defense capacity in leaves while triggering compensatory mechanisms in roots. These findings underscore a concerning interaction between plastic pollution and climate warming in crop plants. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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19 pages, 3457 KiB  
Article
Transcriptome Analysis Revealed the Immune and Metabolic Responses of Grass Carp (Ctenopharyngodon idellus) Under Acute Salinity Stress
by Leshan Ruan, Baocan Wei, Yanlin Liu, Rongfei Mu, Huang Li and Shina Wei
Fishes 2025, 10(8), 380; https://doi.org/10.3390/fishes10080380 - 5 Aug 2025
Viewed by 135
Abstract
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its [...] Read more.
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its physiological adaptations to fluctuating salinity gradients. We used high-throughput mRNA sequencing and differential gene expression profiling to analyze transcriptional dynamics in intestinal and kidney tissues of grass carp exposed to heterogeneous salinity stressors. Concurrent serum biochemical analyses showed salinity stress significantly increased Na+, Cl, and osmolarity, while decreasing lactate and glucose. Salinity stress exerted a profound impact on the global transcriptomic landscape of grass carp. A substantial number of co-regulated differentially expressed genes (DEGs) in kidney and intestinal tissues were enriched in immune and metabolic pathways. Specifically, genes associated with antigen processing and presentation (e.g., cd4-1, calr3b) and apoptosis (e.g., caspase17, pik3ca) exhibited upregulated expression, whereas genes involved in gluconeogenesis/glycolysis (e.g., hk2, pck2) were downregulated. KEGG pathway enrichment analyses revealed that metabolic and cellular structural pathways were predominantly enriched in intestinal tissues, while kidney tissues showed preferential enrichment of immune and apoptotic pathways. Rigorous validation of RNA-seq data via qPCR confirmed the robustness and cross-platform consistency of the findings. This study investigated the core transcriptional and physiological mechanisms regulating grass carp’s response to salinity stress, providing a theoretical foundation for research into grass carp’s resistance to salinity stress and the development of salt-tolerant varieties. Full article
(This article belongs to the Special Issue Adaptation and Response of Fish to Environmental Changes)
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20 pages, 4055 KiB  
Article
Biphasic Salt Effects on Lycium ruthenicum Germination and Growth Linked to Carbon Fixation and Photosynthesis Gene Expression
by Xinmeng Qiao, Ruyuan Wang, Lanying Liu, Boya Cui, Xinrui Zhao, Min Yin, Pirui Li, Xu Feng and Yu Shan
Int. J. Mol. Sci. 2025, 26(15), 7537; https://doi.org/10.3390/ijms26157537 - 4 Aug 2025
Viewed by 166
Abstract
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been [...] Read more.
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been proposed as a viable strategy. In the study, we investigated the physiological and molecular responses of Lycium ruthenicum Murr. to varying NaCl concentrations. Results revealed a concentration-dependent dual effect: low NaCl levels significantly promoted seed germination, while high concentrations exerted strong inhibitory effects. To elucidate the mechanisms underlying these divergent responses, a combined analysis of metabolomics and transcriptomics was applied to identify key metabolic pathways and genes. Notably, salt stress enhanced photosynthetic efficiency through coordinated modulation of ribulose 5-phosphate and erythrose-4-phosphate levels, coupled with the upregulation of critical genes encoding RPIA (Ribose 5-phosphate isomerase A) and RuBisCO (Ribulose-1,5-bisphosphate carboxylase/oxygenase). Under low salt stress, L. ruthenicum maintained intact cellular membrane structures and minimized oxidative damage, thereby supporting germination and early growth. In contrast, high salinity severely disrupted PS I (Photosynthesis system I) functionality, blocking energy flow into this pathway while simultaneously inducing membrane lipid peroxidation and triggering pronounced cellular degradation. This ultimately suppressed seed germination rates and impaired root elongation. These findings suggested a mechanistic framework for understanding L. ruthenicum adaptation under salt stress and pointed out a new way for breeding salt-tolerant crops and understanding the mechanism. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 17592 KiB  
Article
Functional Identification of Acetyl-CoA C-Acetyltransferase Gene from Fritillaria unibracteata
by Zichun Ma, Qiuju An, Xue Huang, Hongting Liu, Feiying Guo, Han Yan, Jiayu Zhou and Hai Liao
Horticulturae 2025, 11(8), 913; https://doi.org/10.3390/horticulturae11080913 (registering DOI) - 4 Aug 2025
Viewed by 51
Abstract
Fritillaria unibracteata is a rare and endangered medicinal plant in the Liliaceae family, whose bulbs have been used in traditional Chinese traditional medicine for over 2000 years. The mevalonate (MVA) pathway is involved in the growth, development, response to environmental stress, and active [...] Read more.
Fritillaria unibracteata is a rare and endangered medicinal plant in the Liliaceae family, whose bulbs have been used in traditional Chinese traditional medicine for over 2000 years. The mevalonate (MVA) pathway is involved in the growth, development, response to environmental stress, and active ingredient production of plants; however, the functional characterization of MVA-pathway genes in the Liliaceae family remains poorly documented. In this study, an Acetyl-CoA C-acetyltransferase gene (FuAACT) was first cloned from F. unibracteata. It exhibited structural features of the thiolase family and showed the highest sequence identity with the Dioscorea cayenensis homolog. The Km, Vmax, and Kcat of the recombinant FuAACT were determined to be 3.035 ± 0.215 μM, 0.128 ± 0.0058 μmol/(min·mg), and 1.275 ± 0.0575 min−1, respectively. The optimal catalytic conditions for FuAACT were ascertained to be 30 °C and pH 8.9. It was stable below 50 °C. His361 was confirmed to be a key amino acid residue to enzymatic catalysis by site-directed mutagenesis. Subsequent subcellular localization experiments demonstrated that FuAACT was localized in chloroplasts and cytoplasm. FuAACT-overexpressing transgenic Arabidopsis thaliana plants showed higher drought tolerance than wild-type plants. This phenotypic difference was corroborated by significant differences in seed germination rate, lateral root number, plant height, and leaf number (p < 0.05). Furthermore, the FuAACT transgenic plants resulted in the formation of a more developed fibrous root system. These results indicated that the FuAACT gene revealed substantial biological activity in vitro and in vivo, hopefully providing the basis for its further research and application in liliaceous ornamental and medicinal plants. Full article
(This article belongs to the Special Issue Tolerance of Horticultural Plants to Abiotic Stresses)
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17 pages, 5839 KiB  
Article
Salvianolic Acid A Activates Nrf2-Related Signaling Pathways to Inhibit Ferroptosis to Improve Ischemic Stroke
by Yu-Fu Shang, Wan-Di Feng, Dong-Ni Liu, Wen-Fang Zhang, Shuang Xu, Dan-Hong Feng, Guan-Hua Du and Yue-Hua Wang
Molecules 2025, 30(15), 3266; https://doi.org/10.3390/molecules30153266 - 4 Aug 2025
Viewed by 196
Abstract
Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, [...] Read more.
Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article
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25 pages, 7432 KiB  
Article
Integration of mRNA and miRNA Analysis Reveals the Regulation of Salt Stress Response in Rapeseed (Brassica napus L.)
by Yaqian Liu, Danni Li, Yutong Qiao, Niannian Fan, Ruolin Gong, Hua Zhong, Yunfei Zhang, Linfen Lei, Jihong Hu and Jungang Dong
Plants 2025, 14(15), 2418; https://doi.org/10.3390/plants14152418 - 4 Aug 2025
Viewed by 154
Abstract
Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus [...] Read more.
Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways. Combined with weighted gene co-expression network analysis (WGCNA) and RT-qPCR validation, five candidate genes (WRKY6, WRKY70, NHX1, AVP1, and NAC072) were identified as the regulators of salt tolerance in rapeseed. Haplotype analysis based on association mapping showed that NAC072, ABI5, and NHX1 exhibited two major haplotypes that were significantly associated with salt tolerance variation under salt stress in rapeseed. Integrated miRNA-mRNA analysis and RT-qPCR identified three regulatory miRNA-mRNA pairs (bna-miR160a/BnaA03.BAG1, novel-miR-126/BnaA08.TPS9, and novel-miR-70/BnaA07.AHA1) that might be involved in S268 salt tolerance. These results provide novel insights into the post-transcriptional regulation of salt tolerance in B. napus, offering potential targets for genetic improvement. Full article
(This article belongs to the Special Issue Applications of Bioinformatics in Plant Science)
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16 pages, 1313 KiB  
Article
Mycorrhizas Promote Total Flavonoid Levels in Trifoliate Orange by Accelerating the Flavonoid Biosynthetic Pathway to Reduce Oxidative Damage Under Drought
by Lei Liu and Hong-Na Mu
Horticulturae 2025, 11(8), 910; https://doi.org/10.3390/horticulturae11080910 (registering DOI) - 4 Aug 2025
Viewed by 137
Abstract
Flavonoids serve as crucial plant antioxidants in drought tolerance, yet their antioxidant regulatory mechanisms within mycorrhizal plants remain unclear. In this study, using a two-factor design, trifoliate orange (Poncirus trifoliata (L.) Raf.) seedlings in the four-to-five-leaf stage were either inoculated with Funneliformis [...] Read more.
Flavonoids serve as crucial plant antioxidants in drought tolerance, yet their antioxidant regulatory mechanisms within mycorrhizal plants remain unclear. In this study, using a two-factor design, trifoliate orange (Poncirus trifoliata (L.) Raf.) seedlings in the four-to-five-leaf stage were either inoculated with Funneliformis mosseae or not, and subjected to well-watered (70–75% of field maximum water-holding capacity) or drought stress (50–55% field maximum water-holding capacity) conditions for 10 weeks. Plant growth performance, photosynthetic physiology, leaf flavonoid content and their antioxidant capacity, reactive oxygen species levels, and activities and gene expression of key flavonoid biosynthesis enzymes were analyzed. Although drought stress significantly reduced root colonization and soil hyphal length, inoculation with F. mosseae consistently enhanced the biomass of leaves, stems, and roots, as well as root surface area and diameter, irrespective of soil moisture. Despite drought suppressing photosynthesis in mycorrhizal plants, F. mosseae substantially improved photosynthetic capacity (measured via gas exchange) and optimized photochemical efficiency (assessed by chlorophyll fluorescence) while reducing non-photochemical quenching (heat dissipation). Inoculation with F. mosseae elevated the total flavonoid content in leaves by 46.67% (well-watered) and 14.04% (drought), accompanied by significantly enhanced activities of key synthases such as phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), 4-coumarate:coA ligase (4CL), and cinnamate 4-hydroxylase (C4H), with increases ranging from 16.90 to 117.42% under drought. Quantitative real-time PCR revealed that both mycorrhization and drought upregulated the expression of PtPAL1, PtCHI, and Pt4CL genes, with soil moisture critically modulating mycorrhizal regulatory effects. In vitro assays showed that flavonoid extracts scavenged radicals at rates of 30.07–41.60% in hydroxyl radical (•OH), 71.89–78.06% in superoxide radical anion (O2•−), and 49.97–74.75% in 2,2-diphenyl-1-picrylhydrazyl (DPPH). Mycorrhizal symbiosis enhanced the antioxidant capacity of flavonoids, resulting in higher scavenging rates of •OH (19.07%), O2•− (5.00%), and DPPH (31.81%) under drought. Inoculated plants displayed reduced hydrogen peroxide (19.77%), O2•− (23.90%), and malondialdehyde (17.36%) levels. This study concludes that mycorrhizae promote the level of total flavonoids in trifoliate orange by accelerating the flavonoid biosynthesis pathway, hence reducing oxidative damage under drought. Full article
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17 pages, 972 KiB  
Article
SARS-CoV-2 Main Protease Dysregulates Hepatic Insulin Signaling and Glucose Uptake: Implications for Post-COVID-19 Diabetogenesis
by Praise Tatenda Nhau, Mlindeli Gamede, Andile Khathi and Ntethelelo Sibiya
Pathophysiology 2025, 32(3), 39; https://doi.org/10.3390/pathophysiology32030039 - 4 Aug 2025
Viewed by 129
Abstract
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, [...] Read more.
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (Mpro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of Mpro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of Mpro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 Mpro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the Mpro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under Mpro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 Mpro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article
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21 pages, 5496 KiB  
Article
Optimisation of Response Surface Methodology Based on Finite Element Analysis for Laser Cladding of Highly Hardened WC(Co,Ni) Coatings
by Dezheng Wu, Canyu Ding and Mingder Jean
Materials 2025, 18(15), 3658; https://doi.org/10.3390/ma18153658 - 4 Aug 2025
Viewed by 189
Abstract
In the present work, the optimization of ceramic-based composite WC(Co,Ni) welds by laser cladding was carried out using response surface methodology based on finite element analysis. The heat distribution and temperature field of laser-melted WC(Co,Ni) ceramic coatings were simulated using ANSYS software, which [...] Read more.
In the present work, the optimization of ceramic-based composite WC(Co,Ni) welds by laser cladding was carried out using response surface methodology based on finite element analysis. The heat distribution and temperature field of laser-melted WC(Co,Ni) ceramic coatings were simulated using ANSYS software, which allowed the computation of the distribution of residual stresses. The results show that the isotherms in the simulation of the temperature field are elliptical in shape, and that the isotherms in front of the moving heat source are dense with a larger temperature gradient, while the isotherms behind the heat source are sparse with a smaller temperature gradient. In addition, the observed microstructural evolution shows that the melting zone domains of WC(Co,Ni) are mainly composed of unmelted carbides. These carbides are dendritic, rod-like, leaf-like, or net-like, and are agglomerated into smaller groups. The W content of these unmelted carbides exceeds 80%, while the C content is around 1.5–3.0%. The grey areas are composed of WC, Co and Ni compounds. Based on the regression model, a quadratic model was successfully constructed. A three-dimensional profile model of the residual stress behaviour was further explored. The estimated values of the RSM-based FEA model for residual stress are very similar to the actual results, which shows that the model is effective in reducing residual stress by laser cladding. Full article
(This article belongs to the Special Issue Advances in Plasma and Laser Engineering (Second Edition))
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18 pages, 3891 KiB  
Review
Navigating Brain Organoid Maturation: From Benchmarking Frameworks to Multimodal Bioengineering Strategies
by Jingxiu Huang, Yingli Zhu, Jiong Tang, Yang Liu, Ming Lu, Rongxin Zhang and Alfred Xuyang Sun
Biomolecules 2025, 15(8), 1118; https://doi.org/10.3390/biom15081118 - 4 Aug 2025
Viewed by 266
Abstract
Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial [...] Read more.
Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article
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18 pages, 1256 KiB  
Article
Algae Extracts and Zeolite Modulate Plant Growth and Enhance the Yield of Tomato Solanum lycopersicum L. Under Suboptimum and Deficient Soil Water Content
by José Antonio Miranda-Rojas, Aurelio Pedroza-Sandoval, Isaac Gramillo-Ávila, Ricardo Trejo-Calzada, Ignacio Sánchez-Cohen and Luis Gerardo Yáñez-Chávez
Horticulturae 2025, 11(8), 902; https://doi.org/10.3390/horticulturae11080902 (registering DOI) - 3 Aug 2025
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Abstract
Drought and water scarcity are some of the most important challenges facing agricultural producers in dry environments. This study aimed to evaluate the effect of algae extract and zeolite in terms of their biostimulant action on water stress tolerance to obtain better growth [...] Read more.
Drought and water scarcity are some of the most important challenges facing agricultural producers in dry environments. This study aimed to evaluate the effect of algae extract and zeolite in terms of their biostimulant action on water stress tolerance to obtain better growth and production of tomato Lycopersicum esculentum L. grown in an open field under suboptimum and deficient soil moisture content. Large plots had a suboptimum soil moisture content (SSMC) of 25% ± 2 [28% below field capacity (FC)] and deficient soil moisture content (DSMC) of 20% ± 2 [11% above permanent wilting point (PWP)]; both soil moisture ranges were based on field capacity FC (32%) and PWP (18%). Small plots had four treatments: algae extract (AE) 50 L ha−1 and zeolite (Z) 20 t ha−1, a combination of both products (AE + Z) 25 L ha−1 and 10 t h−1, and a control (without application of either product). By applying AE, Z, and AE + Z, plant height, plant vigor, and chlorophyll index were significantly higher compared to the control by 20.3%, 10.5%, and 22.3%, respectively. The effect on relative water content was moderate—only 2.6% higher than the control applying AE, while the best treatment for the photosynthesis variable was applying Z, with a value of 20.9 μmol CO2 m−2 s−1, which was 18% higher than the control. Consequently, tomato yield was also higher compared to the control by 333% and 425% when applying AE and Z, respectively, with suboptimum soil moisture content. The application of the biostimulants did not show any mitigating effect on water stress under soil water deficit conditions close to permanent wilting. These findings are relevant to water-scarce agricultural areas, where more efficient irrigation water use is imperative. Plant biostimulation through organic and inorganic extracts plays an important role in mitigating environmental stresses such as those caused by water shortages, leading to improved production in vulnerable agricultural areas with extreme climates. Full article
(This article belongs to the Special Issue Optimized Irrigation and Water Management in Horticultural Production)
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