Search Results (392)

As an essential type of vaccine, live attenuated vaccines (LAVs) play a crucial role in animal disease prevention and control. Nevertheless, developing LAVs faces the challenge of balancing safety and efficacy. Understanding the mechanisms animal viruses use to antagonize host antiviral innate immunity may help to precisely regulate vaccine strains and maintain strong immunogenicity while reducing their pathogenicity. It may improve the safety and efficacy of LAVs, as well as provide a more reliable means for the prevention and control of infectious livestock diseases. Therefore, exploring viral antagonistic mechanisms is a significant clue for developing LAVs, which helps to explore more viral virulence factors (as new vaccine targets) and provides a vital theoretical basis and technical support for vaccine development. Among animal viruses, ASFV, PRRSV, PRV, CSFV, FMDV, PCV, PPV, and AIV are some typical representatives. It is crucial to conduct in-depth research and summarize the antagonistic strategies of these typical animal viruses. Studies have indicated that animal viruses may antagonize the antiviral innate immunity by directly or indirectly blocking the antiviral signaling pathways. In addition, viruses also do this by antagonizing host restriction factors targeting the viral replication cycle. Beyond that, viruses may antagonize via regulating apoptosis, metabolic pathways, and stress granule formation. A summary of viral antagonistic mechanisms might provide a new theoretical basis for understanding the pathogenic mechanism of animal viruses and developing LAVs based on antagonistic mechanisms and viral virulence factors. Full article

Background/Objectives: Amyloid peptides, whose accumulation in the brain as senile plaques is associated with the onset of Alzheimer’s disease, are also found in cerebral vessels and in circulation. In the bloodstream, amyloid peptides promote platelet adhesion, activation, oxidative stress, and thrombosis, contributing to the cardiovascular complications observed in Alzheimer’s disease patients. Natural compounds, such as curcumin, are known to modulate platelet activation induced by the hemostatic stimuli thrombin and convulxin. In this study, we investigated the ability of curcumin to modulate platelet activation triggered by amyloid peptides, and we compared its effects with those displayed on platelet activation induced by physiological agonists. Methods: Commercial ultrapure curcumin was used, and platelet aggregation, granule secretion, phosphorylation of selected signaling proteins, and reactive oxygen species production were analyzed on isolated human platelets. Results: Our results demonstrate that curcumin effectively suppressed platelet aggregation induced by fibrillar amyloid peptides. This effect was associated with the reduction in intracellular signaling pathways involving PKC, PI3K, and MAPK. By contrast, platelet aggregation and activation induced by thrombin and convulxin were only partially reduced by preincubation with curcumin. Moreover, curcumin completely suppressed granule secretion only when platelets were stimulated with hemostatic agonists, but it had no effects upon stimulation with amyloid peptides. Additionally, curcumin reduced the production of reactive oxygen species induced by amyloid peptides with a stronger efficiency compared to platelets stimulated with thrombin. Conclusions: These results indicate that curcumin displays selective and potent inhibitory activity on platelet responses to pathological stimuli, such as fibrillar amyloid peptides. Full article

This study evaluated the properties and processing of cemented paste backfills (CPBs) for potash mining through loop tests. The CPBs were made with steel slags as the binder, granulated potash tailings as the aggregate, and waste brine water as the liquid phase. The effects of solid concentration and steel slag dosage on the transport and mechanical properties of CPBs were assessed. The loop test demonstrated that all CPB slurries performed well, exhibiting strong long-distance pipeline transport capabilities. The 28-day compressive strength of the backfills exceeded 1 MPa, meeting the design requirements for backfill strength. The key rheological parameters, including yield stress (τ₀) and viscosity coefficient (η), were comprehensively and theoretically analyzed based on the variations in pressure loss per unit distance of the filling slurry measured during the loop test. The empirical formulas for CPB pressure loss, accounting for varying flow rates and pipeline diameters, were derived with an error margin under 2%. The response surface analysis showed that the affecting extents of factors on pressure loss in CPB slurry were ranked as follows: solid concentration > cementing agent content > flow rate. This study offered valuable guidance for the processing of potash mine backfill operations. Full article

The pathogenesis of neurodegenerative diseases results from the interplay between genetic and environmental factors. Aging and chronic oxidative stress are critical contributors to neurodegeneration. UBQLN2, a ubiquitin-related protein, aids in protein degradation and protects against oxidative stress. In ALS neurons harboring UBQLN2 mutations, oxidative stress accelerates pathological changes, yet the precise mechanisms remain unclear. Using induced motor neurons (iMNs) derived from UBQLN2 P497H iPSCs, we observed ALS-like phenotypes, including TDP-43 mislocalization, increased cell death, and reduced viability. Sodium arsenite (SA)-induced oxidative stress triggered stress granule formation, while autophagy dysfunction exacerbated neuronal degeneration. CHX and bosutinib treatments reduced ubiquitinated protein accumulation and alleviated degeneration, highlighting potential therapeutic pathways. These findings emphasize the role of chronic oxidative stress and stress granule formation in UBQLN2 ALS, offering insights into novel therapeutic targets. Full article

Unlike many other fungicides, strobilurins are applied several times during the growing season for prophylactic purposes, thus heightening the risk of environmental contamination. In the EU, the dimoxystrobin approval period lasted for 17 years. It has been classified as moderately toxic to birds and highly toxic to earthworms, and it is suspected to be carcinogenic to humans. However, it is still commercialized in several countries. The effects of dimoxystrobin are still largely underexplored, with only three studies reporting sublethal alterations in fish. Here, we evaluated for the first time the effects of dimoxystrobin on zebrafish liver after short-term exposure (96 h) to two sublethal and environmentally relevant concentrations (6.56 and 13.13 μg/L), providing evidence of morphological, functional, and ultrastructural modifications. We revealed severe alterations encompassing three reaction patterns: circulatory disturbance, regressive and progressive changes, which also showed a dose-dependent trend. Furthermore, we revealed that dimoxystrobin induced a significant increase in lipid content, a decrease in glycogen granules and affected the defensive response against oxidative stress through a significant downregulation of SOD and CAT. The information presented here demonstrates that the hazardous properties of dimoxystrobin may result from several pathological events involving multiple targets. Our results also emphasize the importance of the combined use of morphological, ultrastructural and functional investigation in ecotoxicological studies. Full article

To date, seven human coronaviruses (HCoVs) have been identified. Four of these viruses typically manifest as a mild respiratory disease, whereas the remaining three can cause severe conditions that often result in death. The reasons for these differences remain poorly understood, but they may be related to the properties of individual viral proteins. The nucleocapsid (N) protein plays a crucial role in the packaging of viral genomic RNA and the modification of host cells during infection, in part due to its capacity to form dynamic biological condensates via liquid–liquid phase separation (LLPS). In this study, we investigated the capacity of N proteins derived from all HCoVs to form condensates when transiently expressed in cultured human cells. Some of the transfected cells were observed to contain cytoplasmic granules in which most of the N proteins were accumulated. Notably, the N proteins of SARS-CoV and SARS-CoV-2 showed a significantly reduced tendency to form cytoplasmic condensates. The condensate formation was not a consequence of overexpression of N proteins, as is typical for LLPS-inducing proteins. These condensates contained components of stress granules (SGs), indicating that the expression of N proteins caused the formation of SGs, which integrate N proteins. Thus, the N proteins of two closely related viruses, SARS-CoV and SARS-CoV-2, have the capacity to antagonize SG induction and/or assembly, in contrast to all other known HCoVs. Full article

Low temperature, as a major abiotic stress, impacts the formation of high-quality tobacco seedlings. It is urgent to take appropriate measures to improve the low-temperature tolerance of tobacco seedlings. A hydroponics experiment was conducted with a tobacco cv. Y2001 under 25 °C (control temperature) and 10 °C (low-temperature stress). Three phosphorus (P) levels including the traditional P concentration (2 mM PO₄³⁻) and higher P levels (3 mM PO₄³⁻ and 4 mM PO₄³⁻) were applied to investigate their effects on antioxidant metabolism and carbohydrate metabolism in low-temperature-stressed tobacco seedlings. The results showed that the low temperature decreased plant height, stem diameter, and biomass of shoots and roots, while the higher P levels promoted plant height and shoot biomass of low-temperature-stressed tobacco seedlings compared to the traditional P level. The leaf net photosynthetic rate (A_N) was decreased by the low temperature, while the A_N of low-temperature-stressed tobacco leaves was increased by 38.6–61.3% for the higher P levels than the traditional P level. Higher O₂⁻ and H₂O₂ were observed in tobacco leaves exposed to low-temperature stress, damaging the A_N, although the low temperature upregulated the expression of encoding superoxide dismutase (NtSOD), peroxidase (NtPOD), and catalase (NtCAT). However, compared with the traditional P level, the higher P levels further upregulated the expression of NtSOD and NtCAT in low-temperature-stressed tobacco leaves to accelerate O₂⁻ and H₂O₂ removal. Higher leaf sucrose content was detected since the low temperature significantly downregulated the expression of NtSuSy, NtCWINV, and NtNINV encoding sucrose synthase, the cell wall, and alkaline invertases, respectively, inhibiting sucrose hydrolysis. Compared with the traditional P level, higher P levels downregulated the expression of NtCWINV in low-temperature-stressed tobacco leaves, further promoting leaf sucrose content. The low temperature downregulated the expression of NtAGP encoding ADP-glucose pyrophosphorylase, NtSSS encoding soluble starch synthase, and NtGBSS encoding granule-bound starch synthase, thereby restricting starch biosynthesis. Additionally, the low temperature upregulated the expression of α-amylase and β-amylase, accelerating starch hydrolysis. These led to a lower starch content in low-temperature-stressed tobacco leaves. The higher P levels further upregulated the expression of α-amylase in low-temperature-stressed tobacco leaves than the traditional P level, further lowering the starch content. Moreover, the leaf soluble sugar content was higher under the low temperature than the control temperature, which helped the tobacco plants resist low-temperature stress. And higher P levels further promoted the soluble sugar content in low-temperature-stressed tobacco leaves compared with the traditional P level, further improving tobacco seedlings’ low-temperature tolerance. Therefore, these results indicated that increasing the P application level can alleviate the adverse impacts of cold stress on antioxidant metabolism and carbohydrate metabolism in tobacco seedlings. Full article

Stress granules (SGs) are membrane-less aggregates that form in response to various cellular stimuli through a process called liquid–liquid phase separation (LLPS). Stimuli such as heat shock, osmotic stress, oxidative stress, and infections can induce the formation of SGs, which play crucial roles in regulating gene expression to help cells adapt to stress conditions. Various mRNAs and proteins are aggregated into SGs, particularly those associated with the protein translation machinery, which are frequently found in SGs. When induced by infections, SGs modulate immune cell activity, supporting the cellular response against infection. The roles of SGs differ in viral versus microbial infections, and depending on the type of immune cell involved, SGs function differently in response to infection. In this review, we summarize our current understanding of the implication of SGs in immunity and cellular organelles in the context of infectious diseases. Importantly, we explore insights into the regulatory functions of SGs in the context of host cells under infection. Full article

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein (RBP) that plays a multifunctional role in RNA metabolism. TIA1 has three RNA-Recognition Motifs (RRMs) and a prion-like carboxyl C-terminal domain (LCD) with intrinsically disordered regions (IDR) implicated in the dynamics (i.e., formation, assembly, and disassembly) of transient RNA-protein aggregates known as stress granules (SGs). A protein related to TIA1 is its paralog TIA1-related/like protein (TIAR/TIAL1), whose amino acid sequence, structural organisation, and molecular and cellular functions are highly conserved with TIA1. Both proteins are the main components of SGs, which are non-membranous RNA-protein condensates formed under stress to promote cell survival. Welander distal myopathy (WDM) is a late-onset muscular dystrophy that has been linked to a single-nucleotide substitution (c.1362G>A; p.E384K) in the gene encoding the TIA1 protein, which impacts TIA1-dependent SGs dynamics. Herein, we have analysed cellular and molecular aspects by targeting mutagenesis to position 384 to understand its molecular grammar in an amino acid/proteinogenic-dependent or -independent manner under oxidative stress. The observations suggest differential, even opposing, behaviours between TIA1 and TIAR in the presence of specific amino acids with negative and positive charges, and also uncharged acids, at equivalent positions of TIA1 and TIAR, respectively. Collectively, these findings illustrate a characteristic molecular grammar of TIAR- and TIA1-dependent SGs under oxidative conditions, suggesting a gain of versatility between two structurally and functionally highly conserved/related proteins. Full article

Background: Melt-based 3D printing technologies are currently extensively evaluated for research purposes as well as for industrial applications. Classical approaches often require intermediates, which can pose a risk to stability and add additional complexity to the process. The Advanced Melt Drop Deposition (AMDD) technology, is a 3D printing process that combines the principles of melt extrusion with pressure-driven ejection, similar to injection molding. This method offers several advantages over traditional melt-based 3D printing techniques, making it particularly suitable for pharmaceutical applications. Objectives: This study evaluates the AMDD printing system for producing solid oral dosage forms, with a primary focus on the thermo-stable polymer polyvinyl alcohol (PVA). The suitability of AMDD technology for creating amorphous solid dispersions (ASDs) is also examined. Finally, the study aims to define the material requirements and limitations of the raw materials used in the process. Methods: The active pharmaceutical ingredients (APIs) indometacin and ketoconazole were used, with PVA 4-88 serving as the carrier polymer. Powders, wet granulates, and pellets were investigated as raw materials and characterized. Dissolution testing and content analyses were performed on the printed dosage forms. Solid-state characterization was conducted using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Degradation due to thermal and mechanical stress was analyzed using nuclear magnetic resonance spectroscopy (NMR). Results/Conclusions: The results demonstrate that the AMDD 3D printing process is well-suited for producing solid dosage forms. Tablets were successfully printed, meeting mass uniformity standards. Adjusting the infill volume from 30% to 100% effectively controlled the drug release rate of the tablets. Solid-state analysis revealed that the AMDD process can produce amorphous solid dispersions with enhanced solubility compared to their crystalline form. The experiments also demonstrated that powders with a particle size of approximately 200 µm can be directly processed using AMDD technology. Full article

The probiotic bacterium Bifidobacterium animalis subsp. lactis BB-12 (BB-12) was encapsulated in two composites, alginate/agar and alginate/agar/casein. The network structure and physicochemical properties of these composites are influenced by complex interactions, including hydrogen bonding, electrostatic forces between biopolymers, calcium ions, and the encapsulated bacteria. The composites demonstrated a granular surface, with the granules being spatially oriented on the alginate/agar/BB-12 surface and linearly oriented on the alginate/agar/casein/BB-12 surface. They possess a highly organized microparticle structure and exhibit viscoelastic solid-like behavior. The alginate/agar/BB-12 composite showed higher storage modulus, shear stress, and shear strain values, indicating enhanced stability in various physical environments. Both composites displayed good thermal stability, aligning with their rheological properties, confirming their well-ordered structures. Despite differences in composite structures, the release mechanism of bacteria is governed by Fickian diffusion through the composite matrix. Based on physicochemical properties, the alginate/agar/casein composite is recommended for dairy product fermentation, while the alginate/agar composite seems more suitable for oral use. These findings provide new insights into the interactions between bacterial cultures and alginate composite ingredients. Full article

Background/Objectives: Improving the production rates of modern tablet presses places ever greater demands on the performance of excipients. Although co-processing has emerged as a promising solution, there is still a lack of directly compressible excipients for modified-release formulations. The aim of the present study was to address this issue by investigating the potential of novel co-processed excipients for the manufacture of modified-release tablets containing ibuprofen. Methods: The excipients were prepared by melt granulation of lactose monohydrate with glyceryl palmitostearate as a binder. The influence of glyceryl palmitostearate particle size, ibuprofen content, compression pressure, and compression speed on the compaction behavior of the tablet blends was analyzed. Results: Novel co-processed excipients ensured good flowability and acceptable mechanical properties of the tablets containing up to 70% ibuprofen. Furthermore, lipid-based co-processed excipients proved to be very promising for directly compressible formulations with high-dose, highly adhesive active pharmaceutical ingredients such as ibuprofen, as they do not require additional lubricants. The influence of compression speed on the tensile strength of the tablets prepared was not pronounced, indicating the robustness of these directly compressible excipients. The investigated lipid-based excipients enabled a prolonged release of ibuprofen over 10 h. Conclusions: The novel lipid-based co-processed excipients have shown great potential for directly compressible formulations with modified release of high-dose, challenging active pharmaceutical ingredients. Full article

Two novel membranes based on collagen and two polyphenols, taxifolin pentaglutarate (TfG5) and a conjugate of taxifolin with glyoxylic acid (DfTf), were prepared. Fourier transform infrared spectroscopy examination confirmed the preservation of the triple helical structure of collagen. A scanning electron microscopy study showed that both materials had a porous structure. The incorporation of DfTf into the freeze-dried collagen matrix increased the aggregation of collagen fibers to a higher extent than the incorporation of TfG5, resulting in a more compact structure of the material containing DfTf. It was found that NIH/3T3 mouse fibroblasts were attached to, and relatively evenly spread out on, the surface of both newly obtained membranes. In addition, it was shown that the membranes enhanced skin wound healing in rats with a chemical burn induced by acetic acid. The treatment with the materials led to a faster reepithelization and granulation tissue formation compared with the use of other agents (collagen without polyphenols and buffer saline). It was also found that, in the wound tissue, the level of thiobarbituric acid reactive substances (TBARS) was significantly higher and the level of low-molecular-weight SH-containing compounds (RSH) was significantly lower than those in healthy skin, indicating a rise in oxidative stress at the site of injury. The treatment with collagen membranes containing polyphenols significantly decreased the TBARS level and increased the RSH level, suggesting the antioxidant/anti-inflammatory effect of the materials. The membrane containing TfG5 was more effective than other ones (the collagen membrane containing DfTf and collagen without polyphenols). On the whole, the data obtained indicate that collagen materials containing DfTf and TfG5 have potential as powerful therapeutic agents for the treatment of burn wounds. Full article

Anticancer drugs cause anemia in patients through eryptosis and hemolysis. We thus studied the in vitro toxicity of galangin (GAL) in red blood cells (RBCs). RBCs were exposed to 50–500 μM of GAL and analyzed for markers of eryptosis and hemolysis. Ca²⁺ nucleation, phosphatidylserine (PS) externalization, oxidative stress, and cell size were detected via fluorescence-activated cell sorting using Fluo4/AM, annexin-V-FITC, 2′,7′-dichlorodihydrofluorescein diacetate, and forward scatter (FSC), respectively. Acetylcholinesterase (AChE) activity was measured via Ellman’s assay and ultrastructural morphology was examined via scanning electron microscopy. Membrane rupture and extracellular hemoglobin, aspartate transaminase (AST), and lactate dehydrogenase (LDH) were assessed via colorimetric methods. Distinct experiments were carried out to identify protective agents and signaling pathways using small-molecule inhibitors. GAL triggered sucrose-sensitive hemolysis with AST and LDH leakage, increased annexin-V-FITC and Fluo4 fluorescence, and decreased FSC and AChE activity which was associated with the formation of granulated echinocytes. Ca²⁺ omission and energy replenishment with glucose, adenine, and guanosine blunted PS externalization and preserved cellular volume. Moreover, caffeine, Trolox, heparin, and uric acid had similar ameliorative effects. Hemolysis was abrogated via caffeine, Trolox, heparin, mannitol, lactate, melatonin, and PEG 8000. Notably, co-treatment of cells with GAL and staurosporin, D4476, or acetylsalicylic acid prevented PS externalization whereas only the presence of SB203580 and NSC23766 rescued the cells from GAL-induced hemolysis. Ca²⁺ nucleation and metabolic collapse mediated by PKC/CK1α/COX/p38/Rac1 drive GAL-induced eryptosis and hemolysis. These novel findings carry ramifications for the clinical prospects of GAL in anticancer therapy. Full article

It is of great interest to utilize saline fields to promote rice production in China. It has still not been established how salinity stress affects grain-filling characteristics and the relationships with yield formation of rice in a saline field. This experiment was conducted with Ningjing 7 (salinity-tolerant rice variety) and Wuyunjing 30 (salinity-susceptible rice variety) in a non-saline field and a high-saline field in 2021 and 2022. The grain yields of Ningjing 7 and Wuyunjing 30 in a high-saline field were 37.7% and 49.8% lower (p < 0.05) than in a non-saline field across two years. Ningjing 7 exhibited a higher (p < 0.05) grain yield than Wuyunjing 30 in a high-saline field. The reductions in filled-grain percentage and grain weight in inferior grains were greater than in superior grains of Ningjing 7 and Wuyunjing 30. For Ningjing 7 and Wuyunjing 30, the total starch contents in superior and inferior grains at 15, 30, and 45 days after heading were reduced (p < 0.05) in a high-saline field compared to a non-saline field. The ADP–glucose pyrophosphorylase, granule-bound starch synthase, and starch synthase activities after heading in superior and inferior grains in a high-saline field were lower (p < 0.05) than those in a non-saline field, and the reductions were more pronounced for Wuyunjing 30. The maximum grain-filling rate and mean grain-filling rate were decreased, while the time to achieve the maximum grain-filling rate was increased in a high-saline field compared to a non-saline field, especially for Wuyunjing 30. The mean grain-filling rate and grain-filling amount in superior and inferior grains during the early, middle, and late stages were lower in a high-saline field than in a non-saline field. For Ningjing 7 and Wuyunjing 30, the reductions in the grain-filling amount in the inferior grains during the early, middle, and late stages in a high-saline field were greater than those in superior grains. Our results suggest that salinity stress inhibited the grain-filling rate, reduced the total starch content and affected key enzyme activities, which led to the poor sink-filling efficiency and yield performance of rice in a saline field, especially for the salinity-susceptible variety. Full article