Search Results (638)

Soil salinity severely threatens soybean productivity worldwide. While transcriptional responses to salt stress are well-documented, the role of post-transcriptional regulation, particularly alternative splicing (AS), remains underexplored. This study combines physiological phenotyping, transcriptome-wide analysis, and molecular genetics to uncover the mechanisms behind the differences in salt tolerance between the salt-sensitive variety Huachun 6 (HC6) and the resistant variety Fiskeby III. Under salt stress, Fiskeby III exhibited superior survival rates and maintained ion homeostasis, as evidenced by a lower Na⁺/K⁺ ratio, compared with HC6. Transcriptomic and splicing analysis revealed extensive salt-induced alternative splicing reprogramming. Genes undergoing differential AS were enriched in pathways related to stress response, ion transport, and RNA splicing. Based on the overlap with both differentially expressed genes (DEG) and alternative splicing (DAS) genes under salt stress, a key splicing factor, GmSR34b, was identified as a central regulator of AS under salt stress. Under NaCl stress, the expression of GmSR34b in leaves peaked at 1 h and a salt stress-specific splicing variant was rapidly induced. A comparative analysis showed that the Fiskeby III cultivar prioritized maintenance of the full-length transcript during prolonged stress, whereas the HC6 cultivar accumulated higher levels of the splicing variant. This indicates differences in the regulation of alternative splicing between these two cultivars. Functional validation confirmed that overexpression of GmSR34b in soybean hairy roots inhibited salt tolerance. This study provides novel insights into the molecular mechanisms of salt tolerance in soybean, suggesting potential strategies for breeding resilient crops through the manipulation of splicing regulators. Full article

Microalgae, such as Euglena cantabrica, are rich in secondary metabolites, including polyphenols, which are valued for their antioxidant and therapeutic properties. Here a rapid, cost-effective and efficient protocol using a trichloroacetic acid (TCA) solution was developed for the production of an extract from E. cantabrica (EuPoly). The potential environmental and biomedical applications of this new extract were evaluated. The effects of EuPoly extract were tested on normal human dermal fibroblasts (NHDFs) and on breast cancer cells of the triple-negative MDA-MB-231 cell line. EuPoly was able to increase the NHDFs survival in oxidative -stress conditions and, on the contrary, to induce a decrease in cell viability of the breast cancer cells. EuPoly was also used to functionalize frustules (FEuPoly), mesoporous silica structures from diatoms. FEuPoly were investigated for the complexation of Cu²⁺ and Ni²⁺, as new potential tools for metal-ion decontamination. Finally, the scaffolding properties of FEuPoly were here assessed in the bone marrow mesenchymal stem cells (BM-MSCs) growth and their osteo-differentiation. This study provides new insights into the sustainable valorization of algae extracts, showing that TCA E. cantabrica extract and functionalized frustules may serve as multifunctional, eco-friendly resources for biomedical applications, as antioxidants and cancer cell inhibitor, metal ions-trapping and tissue osteo-repair. Full article

Among many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe³⁺ in vertebrate blood. Neisseria meningitidis, a Gram-negative pathogen causing meningitis, relies on iron for survival and acquires it from human transferrin (hTf) using two surface proteins, TbpA and TbpB. These proteins interact with hTf to form a ternary TbpA–TbpB–hTf complex, enabling iron capture from the host. The absence of an experimental crystal structure for this complex has hindered computational studies, a detailed understanding of Fe³⁺ dissociation, and designing efficient therapeutics. This study presents the first computational model of the ternary complex, its validation, and molecular dynamics simulations. Structural analyses revealed key electrostatic interactions regulating Fe³⁺ coordination and essential contact regions between proteins. The role of Lys359 from TbpA was investigated via QM/MM calculations by evaluating Fe³⁺ binding energies of isolated hTf, the ternary complex, and Lys359Ala, Lys359Arg, Lys359Asp mutant models. Results revealed that the proton transfer from Lys359 leads to disruption of Tyr517–Fe³⁺ coordination, facilitating iron transfer to the bacterial system. Natural bond orbital analysis confirmed this mechanism. The findings provide new molecular insight into N. meningitidis iron acquisition and identify Lys359 as a potential target for covalent inhibitor design, guiding the development of novel therapeutics against meningococcal infection. Full article

Salinity is one of the most critical environmental factors for fish, influencing their reproduction, growth, and physiological and metabolic activities. Lateolabrax japonicus is a major commercially important marine fish that has been widely cultured in China. However, there are few reports on the growth tolerance of fish juveniles of different species under various salinity conditions. In this study, we investigated the effects of acute low-salt stress on the survival, plasma osmolality, blood ion concentration, and Na⁺/K⁺-ATPase (NKA) activity in L. japonicus juveniles of two size groups. Our findings revealed no significant difference in survival rates between 5 cm and 10 cm juveniles at salinities of 0.2, 1, 3, 5, 10, 15, and 25. Plasma osmolality and blood ions exhibited a “decrease-increase-stabilization” pattern; 5 cm juveniles stabilized at 6 h at all salinities, whereas 10 cm juveniles required 48 h to stabilize at a salinity of 1, with isosmotic points of 10.91 and 11.00, respectively. Gill and kidney NKA activity followed an “increase-decrease-stabilization” pattern, with 5 cm juveniles achieving stability 12–24 h earlier than 10 cm individuals under low salinities (1, 3, 5). In conclusion, 5 cm L. japonicus juveniles exhibited superior low-salinity tolerance, accelerated osmoregulatory responses, and enhanced adaptation compared to 10 cm juveniles. These findings strongly support the prioritizing of smaller-sized L. japonicus for low-salinity aquaculture practices. Full article

Panulirus ornatus, the ornate spiny lobster, is a stenohaline weak hyper-osmoregulator, yet its osmoregulatory response to salinity stress remains poorly understood. This study investigated six osmoregulatory genes—Na⁺/K⁺-ATPase (nka), V-type H⁺-ATPase (vhe), Na⁺/HCO₃⁻ exchanger (nbc), Na⁺/K⁺/2Cl⁻ co-transporter (nkcc), Na⁺/H⁺ exchanger (nhe), and carbonic anhydrase (ca)—in juvenile gills exposed to 25 ppt, 34 ppt (control), and 40 ppt salinities during acute (48 h) and chronic (>38 d) phases. Transcriptome analysis revealed that all genes were unresponsive following either 25 ppt or 40 ppt salinity acute exposure. However, nkcc showed a tendency toward for upregulation under 25 ppt salinity during acute exposure. Additionally, glutathione S-transferase and putative ferrous reductase 1 were upregulated under 25 ppt salinity, suggesting increased metabolic demand. In contrast, glutathione peroxidase and an ammonia transporter were upregulated in 40 ppt salinity, indicating protein catabolism. Quantitative PCR confirmed nkcc- and nka upregulation under chronic 25 ppt salinity. Vhe, nbc, nhe and ca showed no response, and 40 ppt salinity did not affect the six target genes. These findings suggest P. ornatus relies on nkcc- and nka-mediated ion transport and lacks mechanisms to tolerate high salinity, resulting in reduced growth and survival. These findings define optimal salinity range for aquaculture (25–34 ppt), highlighting the need to avoid high-salinity stress in lobster water quality management Full article

Among existing radiobiological models, the MKM and its extensions (SMK and OSMK) have demonstrated strong predictive capabilities but remain computationally demanding. To address this, we present pyMKM v0.1.0, an open-source Python package for the generation of microdosimetric tables and radiobiological quantities based on these models. The package includes modules for track structure integration, saturation and stochastic corrections, oxygen modulation, and survival fraction computation. Validation was conducted against multiple published datasets across various ion species, LET values, and cell lines under both normoxic and hypoxic conditions. Quantitative comparisons showed high agreement with reference data, with average log errors typically below 0.06 and symmetric mean absolute percentage errors under 2%. The software achieved full unit test coverage and successful execution across multiple Python versions through continuous integration workflows. These results confirm the numerical accuracy, structural robustness, and reproducibility of pyMKM. The package provides a transparent, modular, and extensible tool for microdosimetric modeling in support of radiobiological studies, Monte Carlo-based dose calculation, and biologically guided treatment planning. Full article

Background/Objectives: Esterases are widely used in various industrial fields. This study aimed to isolate and characterize esterase genes from Laceyella sacchari HS49-1, a thermophilic bacterium from a hot spring, which can survive at 45–60 °C and pH 5-10 with robust esterase activity. Methods: A genomic shotgun library was constructed to identify three esterase genes: two in family XII (Est2 and Est7) and one in family VIII (Est1). Sequence analysis revealed significant divergence from other genera. Only Est1 was successfully expressed in Escherichia coli. Its activity, optimal conditions, thermostability, and structure were investigated using p-NP butyrate, temperature/pH assays, heating pre-treatment, and fluorescence quenching. Results: Est1 demonstrated high activity (57.43 ± 0.04 U/mg) towards short-chain p-NP butyrate (C4). Molecular-docking analyses revealed that Est1’s catalytic motif (GXSXG) interacts with various p-NP esters, with binding energy and interaction types varying by acyl chain length. The optimal temperature was 60 °C, and the optimal pH was 8. Est1 exhibited excellent thermostability, retaining 90% of its activity after pre-treatment at 50 °C for 8 h and 69.8% after pre-treatment at 80 °C for the same duration. Fluorescence quenching showed that after 1 h at 80 °C, the fluorescence was reduced by only 16.6%, indicating remarkable heat resistance. Additionally, Est1 did not require metal ions as cofactors and maintained 74.8% of its activity in the presence of 0.1% SDS. Conclusions: The unique properties of Est1 from L. sacchari HS49-1 highlight its potential for industrial applications. Further exploration of this thermophilic bacterium could uncover more valuable genes. Full article

Introduction: The work presented here is part of our study series aimed at investigating the countermeasure effectiveness of apigenin (AP) against both early and late effects of heavy silicon (²⁸Si) on the same cohort of exposed male C57BL/6 mice. We previously reported the countermeasure of AP against ²⁸Si-induced early effects of ²⁸Si ions. This section focuses on the protective effects of AP on late effects, specifically on the induction of acute lymphoma/lymphoblastic leukemia. Method: Mice received a diet containing 20 mg/kg body weight of AP for five days before and after total-body irradiation with either 0 or 0.5 Gy of 260 MeV ²⁸Si ions. They were divided into four groups based on AP intake and irradiation status. At one-week after irradiation, six mice from each group were euthanized to assess AP’s effectiveness against early inflammation (in the bone marrow and gut tissues) and gut dysbiosis. The remaining mice were monitored until approximately 770 days of age. Incidence rates were analyzed using Chi-Square tests, while survival data were evaluated with Kaplan–Meier plots and log-rank tests, setting significance at p ≤ 0.05. Results: At 770 days, survival rates were 37% for ²⁸Si-exposed mice and 63% for those consuming AP, despite irradiation. There was a 2.57-fold increase in acute lymphoma/lymphoblastic leukemia incidence among ²⁸Si-exposed mice not receiving AP compared to controls and AP-fed mice. Together with our previous report on the countermeasure activity of AP against early effects, these findings suggest that the gut–bone marrow axis plays an important role in ²⁸Si-induced acute lymphoma/lymphoblastic leukemia. Conclusion: Our findings demonstrate that AP is an effective means of tackling the challenges posed by space radiation, and it has the potential to revolutionize protection in this critical area. Full article

Salinity is a pivotal environmental factor that significantly influences the survival, growth, development, and reproduction of aquatic organisms. However, the characteristics of serum metabolites and their mechanistic roles in mediating the response of grass carp (Ctenopharyngodon idellus) to long-term salinity stress remain incompletely understood. Therefore, the present study exposed grass carp to different salinity levels (0, 4, and 8 g/L) for 60 days to evaluate the associated physiological alterations and metabolic responses. The results revealed that high salinity (8 g/L) significantly suppressed growth performance (p < 0.05), whereas low salinity (4 g/L) caused no significant reduction in growth or survival. Physiological analyses indicated that fish in the 8 g/L group exhibited markedly reduced levels of lactic acid and total protein, along with elevated concentrations of total cholesterol, triglycerides, glucose, and glutamic-oxaloacetic transaminase (p < 0.05). Serum ion homeostasis was also disrupted under high salinity, characterized by increased Ca²⁺, Na⁺, and Cl⁻ levels and decreased Mg²⁺ (p < 0.05). Furthermore, oxidative stress was evident in the high-salinity group through heightened activities of antioxidant enzymes (SOD, CAT, GPx), accumulation of oxidative damage markers (protein carbonyl, 8-OHdG) (p < 0.05). Metabolomic profiling identified 367 and 403 significantly altered metabolites in the 4 g/L and 8 g/L groups, respectively, primarily belonging to lipids and lipid-like molecules along with organic acids and derivatives. KEGG enrichment analysis revealed that these differential metabolites were chiefly involved in amino acid biosynthesis, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids, and glycine, serine, and threonine metabolism. Trend analysis further uncovered eight distinct expression patterns of metabolites across salinity gradients. These results provide novel insights into the metabolic adaptations of grass carp to salinity stress, demonstrating that high salinity induces oxidative stress, disrupts ion regulation, and drives extensive metabolic reprogramming. The study offers valuable theoretical support for improving salinity tolerance management in aquaculture and informs the selective breeding of salt-tolerant fish strains. Full article

Endometrial cancer is one of the most common malignancies of the female reproductive system, with incidence rising globally due to population ageing and life-style-related risk factors. Calcium (Ca²⁺) is a ubiquitous second messenger regulating diverse physiological processes, and its dysregulation has been increasingly implicated in carcinogenesis, including endometrial. Altered expression and function of Ca²⁺ channels, pumps, exchangers, and binding proteins disrupt the finely tuned balance of Ca²⁺ influx, efflux, and intracellular storage, leading to aberrant signalling that promotes tumour proliferation, migration, survival, and metastasis. This review summarises current knowledge on the molecular “Ca²⁺ toolkit” in the human uterus, highlighting the role of voltage-gated calcium channels (VGCCs), transient receptor potential (TRP) channels, store-operated calcium entry (SOCE) components, Na⁺/Ca²⁺ exchangers, purinergic receptors, P-type ATPases (SERCA, SPCA, PMCA), ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP₃R) receptors, and mitochondrial Ca²⁺ uniporter (MCU) complexes in endometrial cancer progression. Multiple Ca²⁺-handling proteins, including CACNA1D, CACNA2D1, TRPV4, TRPV1, TRPM4, MCU, and RyR1, exhibit cancer-associated overexpression or functional changes, correlating with poor prognosis and aggressive disease features. Emerging evidence supports the therapeutic potential of targeting Ca²⁺ homeostasis using small-molecule inhibitors, ion channel modulators or gene-silencing strategies. These interventions may restore Ca²⁺ balance, induce apoptosis or autophagy, and suppress metastatic behaviour. While no clinical trials have yet explicitly focused on Ca²⁺ modulation in endometrial cancer, the diversity of dysregulated Ca²⁺ pathways offers a rich landscape for novel therapeutic strategies. Targeting key components of the Ca²⁺ signalling network holds promise for improving outcomes in endometrial cancer. Full article

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. This study aimed to evaluate the effectiveness of CIRT in this patient population. Methods: A retrospective analysis was conducted in 76 patients with unresectable RPS treated with CIRT. Of these, 95% had a confirmed prognosis until 2022. In 74 patients, the prescribed relative biological effectiveness dose was 70.4 Gy, delivered in 16 fractions over 4 weeks. Respiratory gating was used, and spot scanning irradiation has been performed in all patients since 2016. Results: The 3- and 5-year overall survival rates for the entire cohort were 68.3% and 49.4%, respectively, with a median overall survival time of 58.1 months. The 3- and 5-year local control rates were 79.0% and 72.0%, respectively. Among 47 naïve patients with treatment-naïve tumors, the 3- and 5-year abdominal recurrence-free survival rates were 51.1% and 29.1%, respectively. Late adverse events of grade 3 or higher occurred in 4 (5.2%) patients. Conclusions: CIRT represents a definitive treatment option for patients with unresectable RPS. In the future, multicenter studies should be conducted to evaluate the effectiveness of CIRT for RPS in larger patient cohorts. Full article

Background/Objectives: Modular dual mobility (MDM) cups are constituted by a cobalt-chromium liner inserted into a standard acetabular shell, allowing for intraoperative indication and supplementary screw fixation of the acetabular component. MDM could face mechanical and biological issues, with the associated risk of elevated blood metal ions levels and adverse local tissue reactions. Methods: This is a monocentric retrospective study on a consecutive series of 105 patients who underwent primary unilateral THA with the G7 Dual Mobility Acetabular System cup (Zimmer Biomet, Warsaw, IN, USA) from March 2019 to April 2023, and who were evaluated clinically and radiographically at a minimum two-year follow-up. All complications and revisions were recorded. Survivorship analysis with any revision surgery as endpoint was performed using Kaplan–Meier survival curves. Results: There were eighty-nine patients (follow-up rate 84.8%) who underwent clinical and radiographic follow-up. The mean follow-up was 2.5 ± 0.8 years. Revision-free survival was 98.0%. Three complications (2.8%) were recorded: one case of posterior dislocation, one periprosthetic joint infection and one post-traumatic periprosthetic femur fracture. Dislocation rate and infection rate were less than 1.0%. None of the patients were revised for adverse local tissue reactions. No cup loosening was observed. No cases of intraprosthetic dislocation, liner malseating or femoral notching were observed. Retroacetabular stress shielding was present in 43.0% of patients. Clinical scores significantly improved at the last follow-up compared with preoperative status (p < 0.0001): the final mean mHHS was 87.5 ± 5.3 and the final mean VAS was 0.5 ± 0.9. Conclusions: The Zimmer G7 modular dual mobility cup appears to be a safe and effective option and does not present specific implant-related mechanical and biological issues in primary total hip arthroplasty at a minimum two-year follow-up. Full article

The voltage-gated proton channel (H_v1) selectively transports protons (H⁺) across biological membranes in response to membrane potential changes. H_v1 is assembled as a dimer, and unlike most voltage-gated ion channels, it lacks a traditional central pore domain; instead, the voltage-sensing domain (VSD) of each monomer facilitates proton conduction via a hydrogen-bond network. H_v1 is widely expressed in various human cell types (e.g., immune cells, sperm, etc.) including tumor cells. In tumor cells, the accumulation of acidic intermediates generated by glycolysis under hypoxic conditions or ROS production leads to significant cytosolic acidification. H_v1 can remove protons from the cytosol rapidly, contributing to the adaptation of the cells to the tumor microenvironment, which may have significant consequences in tumor cell survival, proliferation, and progression. Therefore, H_v1 may be very promising not only as a tumor marker but also as a potential therapeutic target in oncology. Molecules that modulate the proton flux through H_v1 can be divided into two broad groups: inhibitors and activators. H_v1 inhibitors can be simple ions, small molecules, lipids, and peptides. In contrast, fewer H_v1 activators are known, including albumin, NH29, quercetin, and arachidonic acid. The mechanism of action of some inhibitors is well described, but not all. H_v1 modulation has profound effects on cellular physiology, especially under stress or pathological conditions, like cancer and inflammation. The therapeutic application of selective H_v1 inhibitors or activators could be a very promising strategy in the treatment of several serious diseases. Full article

Groundwater is a vital water source for human survival and regulates the hydrological cycle within the uppermost strata. Through the processes of recharge and discharge, as well as solute exchange, it interacts with surface water systems in Zhengzhou, e.g., the Yellow River and the Jialu River. Therefore, systematically assessing its hydrochemical characteristics, driving factors, and health risks is crucial for ensuring the safety of public drinking water and regional development. This study focuses on shallow (45~55 m), medium-deep (80~350 m), deep (350~800 m), and ultra-deep (800~1200 m) groundwater in Zhengzhou City. A descriptive statistical analysis was employed to identify the primary chemical constituents of groundwater at various depths within the study area. Piper diagrams and the Shukarev classification method were employed to determine the hydrochemical types of the groundwater. Additionally, Gibbs diagrams, correlation coefficient methods, ion ratio coefficient methods and chlorine–alkali indices were employed to investigate the formation mechanisms of the chemical components of the groundwater, and the health risks in the study area were evaluated. Results: Ca²⁺ dominates the shallow/medium-deep groundwater, Na⁺ dominates the deep/ultra-deep groundwater; HCO₃⁻ (70~82%) is the dominant anion. Water chemistry shifts from HCO₃-Ca to HCO₃-Na with depth. Solubilisation, cation exchange, counter-cation exchange, and mixed processes primarily govern the formation of the groundwater’s chemical composition in the study area. Nitrate health risk assessments indicate significant differences in non-carcinogenic risks across four population groups (infants, children, young adults, and adults). Medium-depth groundwater poses a potential risk to all groups, while shallow and deep groundwater threaten only infants. Ultra-deep groundwater carries the lowest risk. Full article

Sugarcane wax-derived policosanol (POL) is well recognized for its multifaceted biological activities, particularly in dyslipidemia management, whereas sugar cane extract powder (SEP), prepared from whole sugar juice blended with supplementary components, has not been thoroughly investigated for its biological activities and potential toxicities. Herein, the comparative dietary effect of four distinct SEPs (SEP-1 to SEP-4) and Cuban sugarcane wax extracted POL were examined to prevent the pathological events in high-cholesterol diet (HCD)-induced hyperlipidemic zebrafish. Among the SEPs, a 14-week intake of SEP-2 emerged with the least zebrafish survival probability (0.75, log-rank: χ² = 14.1, p = 0.015), while the POL supplemented group showed the utmost survival probability. A significant change in body weight and morphometric parameters was observed in the SEP-2 supplemented group compared to the HCD group, while non-significant changes had appeared in POL, SEP-1, SEP-3, and SEP-4 supplemented groups. The HCD elevated total cholesterol (TC) and triglyceride (TG) levels were significantly minimized by the supplementation of POL, SEP-1, and SEP-2. However, an augmented HDL-C level was only noticed in POL-supplemented zebrafish. Likewise, only the POL-supplemented group showed a reduction in blood glucose, malondialdehyde (MDA), AST, and ALT levels, and an elevation in sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Also, plasma from the POL-supplemented group showed the highest antioxidant activity and protected zebrafish embryos from carboxymethyllysine (CML)-induced toxicity and developmental deformities. POL effectively mitigated HCD-triggered hepatic neutrophil infiltration, steatosis, and the production of interleukin (IL)-6 and inhibited cellular senescence in the kidney and minimized the ROS generation and apoptosis in the brain. Additionally, POL substantially elevated spermatozoa count in the testis and safeguarded ovaries from HCD-generated ROS and senescence. The SEP products (SEP-1, SEP-3, and SEP-4) showed almost non-significant protective effect; however, SEP-2 exhibited an additive effect on the adversity posed by HCD in various organs and biochemical parameters. The multivariate examination, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), demonstrates the positive impact of POL on the HCD-induced pathological events in zebrafish, which are notably diverse, with the effect mediated by SEPs. The comparative study concludes that POL has a functional superiority over SEPs in mitigating adverse events in hyperlipidemic zebrafish. Full article