Search Results (440)

Verticillium wilt, caused by Verticillium dahliae, is a major constraint on cotton production. The GASA (Gibberellic Acid-Stimulated in Arabidopsis) proteins are cysteine-rich peptides induced by gibberellin signaling; however, their systemic role in upland cotton (Gossypium hirsutum) resistance to Verticillium wilt remains elusive. Here, we identified 40 GhGASA members from the G. hirsutum genome, which were clustered into three subfamilies. All members possessed a typical gibberellin-regulated domain, and segmental duplication was the primary driver of family expansion. Transcriptomic analyses revealed tissue-specific expression, with high abundance in pistils and roots, and distinct responsive patterns to salt, drought, and cold stresses. Quantitative real-time PCR (qRT-PCR) showed that multiple GhGASA genes were significantly upregulated following V. dahliae inoculation, with transcript levels being much higher in roots and stems than in leaves. Notably, GhGASA17, harboring ethylene-responsive elements, was identified as a key candidate involved in the defense response. Overall, this study provides a comprehensive characterization of the GhGASA gene family, offering a theoretical foundation for understanding its regulatory functions in Verticillium wilt resistance and delivering potential genetic resources for molecular breeding in cotton. Full article

Provision of cow–calf contact (CCC) in combination with pair housing may enhance welfare and stimulate greater intake of both milk and starter feed, thereby improving the performance and health of calves reared under cold conditions. This study was conducted to investigate the effects of combining partial daily CCC (5 h/d) with pair housing (19 h/d) in dairy calves reared in outdoor pens during winter, when the mean ambient temperature was 6.2 ± 0.4 °C throughout the study period. A total of 30 Holstein calves (birth weight = 37.4 ± 3.4 kg) were enrolled at birth. Fourteen calves received daily dam contact and were pair-housed (DC-PH), while the remaining 16 calves had no dam contact (NC); of these, 8 were pair-housed (NC-PH) and 8 were individually housed (NC-IH). Dam contact was maintained until day 60, after which all calves were weaned and group-housed until day 80. Milk consumption was greater in DC than NC calves (7.4 vs. 5.5 L/d). During the pre-weaning period, body weight and average daily gain did not differ between treatments. However, DC-PH calves had greater body weight at day 80 and higher average daily gain between days 60 and 80 than NC-PH calves (p = 0.01 and p = 0.02, respectively). Pre-weaning starter feed intake and feed efficiency did not differ across treatment groups. Dry matter digestibility was significantly greater in NC-PH than in NC-IH calves (87.7% vs. 81.4%; p = 0.03), but no significant effects were observed on NDF and DM digestibility between NC-PH and DC-PH calves. On day 54 (the pre-weaning phase), compared with NC-PH calves, DC-PH calves had higher blood glucose (p = 0.05), lower cortisol (p = 0.02), tended to have lower βHBA concentrations (p = 0.06), and a greater ruminal protozoal count on day 35 (p = 0.01). Total health score tended to be higher in DC-PH than NC-PH calves (p = 0.06) and was higher in NC-IH than in NC-PH calves (p = 0.05). During an 8-h behavioral recording prior to weaning, DC-PH calves were observed less frequently performing non-nutritive oral behaviors, such as licking the stall or fences and sucking on other calves, and tended to be more frequently standing, contacting other calves, playing alone, walking, and ruminating than NC-PH calves. After weaning, DC-PH calves were observed more frequently eating, resting, walking, and engaging in social interactions than NC-PH calves. Likewise, after weaning, NC-IH calves were observed more frequently playing, vocalizing, and walking, but less eating than NC-PH calves. Overall, our findings indicated that while social interaction (NC-IH vs. NC-PH) significantly improved dry matter digestibility and health, the addition of dam contact (DC-PH) maintained nutrient digestibility at levels comparable to NC-PH, but tended to reduce health status. Also, calves in the DC-PH treatment, which voluntarily consumed more milk than NC calves, exhibited greater post-weaning growth, more favorable behavioral responses, and improved pre-weaning metabolic profiles (lower cortisol and βHBA concentrations and higher blood glucose). These findings indicate that the partial dam contact management system, together with greater voluntary milk intake, was associated with enhanced post-weaning performance and metabolic status, as well as differences in rumen microbial development. However, as milk intake was not standardized across treatments, these responses cannot be attributed solely to maternal contact. Overall, under the conditions of this study, partial dam contact represents a feasible management strategy to support calf welfare and development, provided that appropriate environmental management is implemented to minimize disease risks. Full article

Cold atmospheric plasma (CAP), a non-thermal ionized gas, is gaining attention in biomedicine due to its unique properties such as the generation of reactive oxygen and nitrogen species (RONS), immunomodulatory effects, and selective cytotoxicity. This review explores the potential of CAP as a therapeutic tool in otorhinolaryngology (ORL). CAP has shown promising applications in wound healing, pathogen eradication, and antitumor strategies, particularly in head and neck cancers. Mechanistically, CAP promotes tissue regeneration through redox signaling, stimulates immune cell activity, induces immunogenic cell death, and enhances epithelial proliferation while offering broad-spectrum antimicrobial efficacy. The review also discusses the development of miniaturized CAP delivery systems, including endoscope-integrated plasma jets (e.g., PLASMASKOP), to facilitate clinical use in anatomically complex ORL regions. Given the nascent stage of clinical translation in ORL, the authors highlight the need for interdisciplinary research and device innovation to realize the full therapeutic potential of CAP in this field. Full article

Photodynamic therapy (PDT) is a reactive oxygen species (ROS)-based treatment modality whose efficacy is often limited by poor photosensitizer stability and delivery. In this study, mesoporous silica-coated iron oxide nanoclusters (MNCs) were synthesized and loaded with protoporphyrin IX (PPIX) to obtain a multifunctional PPIX@MNC nanoplatform. Physicochemical characterization was performed using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). The biological effects of MNC, free PPIX, and PPIX@MNC were evaluated in HaCaT cells—as a general epithelial model—under dark conditions, light irradiation, cold atmospheric plasma (CAP) exposure, and combined CAP-assisted photodynamic treatment. FTIR, DLS, and zeta potential analyses confirmed successful incorporation of PPIX into the nanoclusters. Cell viability assays revealed pronounced phototoxicity of free PPIX, with the IC50 value decreasing from 44.4 ± 3.5 nM under dark conditions to 14 ± 2 nM following light activation, corresponding to a phototoxicity index of 3.17. CAP further enhanced PPIX-mediated cytotoxicity, and the CAP-assisted photodynamic group exhibited the strongest response, with an IC50 value of 9.6 ± 1.1 nM. CAP further enhanced PPIX-mediated cytotoxicity. Increased ROS generation, enhanced apoptosis, and marked mitochondrial membrane potential disruption were observed particularly in CAP-Light-PPIX-treated cells. Although encapsulation of PPIX within MNCs reduced acute cytotoxicity compared with free PPIX, the nanoplatform retained responsiveness to light and CAP stimulation. These findings demonstrate that CAP potentiates PPIX-mediated photodynamic effects through enhanced oxidative stress and suggest that mesoporous silica-coated magnetic nanoclusters represent a promising platform for controlled photosensitizer delivery in CAP-assisted PDT applications. Full article

Obesity-associated metabolic disorders are characterized by impaired glucose and lipid metabolism, insulin resistance, and adipose tissue dysfunction. Interferon regulatory factor 1 (IRF1) is a transcription factor primarily involved in immune regulation; however, its role in adipocyte metabolic regulation remains incompletely understood. In this study, adipocyte-specific Irf1 knockout (Irf1 AKO) mice were generated using the Cre/loxP system and subjected to either a regular chow diet or a high-fat diet (HFD). Metabolic phenotyping, insulin signaling analysis, mitochondrial homeostasis-related assessment, and in vitro adipocyte experiments were performed. Adipocyte-specific IRF1 deficiency improved insulin-stimulated AKT phosphorylation in white adipose tissues and enhanced glucose tolerance and insulin sensitivity under HFD conditions. These metabolic improvements were accompanied by reduced oxygen consumption, energy expenditure, heat production, β3-adrenergic-induced lipolytic response, and cold tolerance. At the molecular level, IRF1 deficiency was associated with reduced TOMM20 expression, decreased mtDNA content, downregulation of oxidative phosphorylation-related genes, and reduced ATP levels in adipose tissues, suggesting altered mitochondrial homeostasis. In 3T3-L1 adipocytes, IRF1 knockdown increased insulin-stimulated AKT activation, glucose uptake, and lipid accumulation, whereas IRF1 overexpression showed opposite trends. Collectively, these findings suggest that adipocyte IRF1 is associated with insulin signaling, lipid metabolic remodeling, and mitochondrial homeostasis, and highlight a potential dissociation between improved insulin responsiveness and reduced energy expenditure in diet-induced obesity. Full article

Frequent marine heatwaves (MHWs) pose significant threats to and have a profound impact on the structure and functioning of marine ecosystems. The response of marine organisms to MHWs may depend on the background temperature of their habitats. Saccharina japonica is a cold-temperate species that is vulnerable to thermal stress. However, it remains unclear how habitat-related temperatures impact responses of S. japonica to MHWs. In this study, the algae were exposed to MHWs (+∆4 °C) under two background temperatures (control level, 8 °C; warmer level, 12 °C), and the growth, photosynthetic performance, and biochemical composition were measured at the end of the MHW and the recovery periods. The results showed that a warmer background temperature increased the growth and pigment contents (Chlorophyll c and fucoxanthin) of S. japonica, but decreased chlorophyll fluorescence parameters, including the effective quantum yield, relative electron transport rate, non-photochemical quenching, and photochemical quenching. The MHWs had no significant effect on growth rate, photosynthetic performance, or biochemical compositions at the background temperature of 8 °C. In contrast, MHWs reduced growth and biochemical composition contents (Chlorophyll a, Chlorophyll c, fucoxanthin and soluble protein) at a warmer level, but the negative influence was alleviated after the recovery period. Furthermore, there was a considerable increase in the total antioxidative capacity caused by MHWs under warmer conditions. Overall, the stimulation in growth demonstrated that warmer conditions (12 °C) may provide a better growth temperature for young S. japonica but also increase the risks of biomass losses and physiological damage triggered by MHWs. These findings deepen our understandings of the tolerance and resistance of S. japonica to heatwaves and provide useful information for managing and modulating the cultivation of this important commercial seaweed. Full article

Purpose: Systemic immunotherapy is less effective in patients with liver metastases. Immunoembolization could potentially overcome the immunosuppressive tumor microenvironment, but the optimal immunotherapy agent, embolic, and release kinetics are unknown. Methods: A wide range of immunotherapy agents (cytokines, small molecules, and oligonucleotides) were loaded onto various embolics (stabilized lipiodol emulsions, microspheres-in-lipiodol, LC beads, and PLGA microspheres). Drug loading and release kinetics were evaluated in vitro. A pilot study of transarterial immunoembolization was performed in a pig liver tumor model, using extended release lipiodol/CpG-STAT3ASO formulations. CpG-STAT3ASO is a first-in-class dual-function immunotherapy agent that both stimulates the anti-tumor immune response, and counters immunosuppression in immunologically cold tumors. Safety, pharmacokinetics and efficacy were evaluated in pigs. Results: Immunotherapy-loaded embolics released drug with a half-life ranging from days to weeks in vitro, and up to four days in pig liver tumors (depending on the formulation). A stabilized lipiodol emulsion demonstrated 100% burst release (within five minutes after immunoembolization), compared to <1% burst release with microspheres-in-lipiodol. Immunoembolization using lipiodol/CpG-STAT3ASO resulted in decreased size of pig liver tumors, compared to bland embolization. No adverse events were seen, based on clinical, laboratory, and radiographic evaluation, but peritoneal adhesions were observed in association with immunoembolization using microspheres-in-lipiodol. Conclusions: Extended-release immunotherapy-loaded embolics generate sustained intratumoral delivery of immune stimulants. A pilot study of immunoembolization of pig liver tumors showed decreased tumor size, compared to bland embolization, with no autoimmune adverse events. Full article

Cold atmospheric plasma (CAP) is a promising tool used in medicine due to its broad spectrum of biological activity and the possibility of safe application on living tissues without the risk of thermal damage. CAP is a partially ionised gas containing electrons, ions and reactive oxygen and nitrogen species (RONS); it also emits ultraviolet radiation and an electromagnetic field. The aim of this study is to discuss the mechanisms of action of cold atmospheric plasma and to assess its significance in supporting the skin healing process. Analysis of the available data indicates that CAP acts in multiple ways: it stimulates the proliferation and migration of keratinocytes and fibroblasts, modulates the inflammatory response, exhibits antimicrobial properties, and improves microcirculation and enhances angiogenesis. The results of studies to date suggest that cold atmospheric plasma may provide valuable support for therapies, particularly in the context of skin regeneration, wound healing and the treatment of inflammatory lesions. However, further research is needed on the standardisation of treatment parameters, long-term safety, and the precise definition of indications and contraindications depending on the type of device used. Full article

P4-ATPases maintain transbilayer lipid asymmetry, yet their functional roles in legume crops remain poorly understood. In the present study, GmALA1 a plasma membrane-localized P4-ATPase in soybean, was identified and characterized. Its physical interaction with the β-subunit GmALIS2 at the plasma membrane via biomolecular fluorescence complementation was confirmed. Heterologous expression in the P4-ATPase-deficient yeast strain ZHY709 demonstrated that GmALA1 fully complemented the cold-sensitive growth phenotype, while co-expression with GmALIS2 only partially restored growth, suggesting GmALIS2 may modulate rather than simply stimulate GmALA1 activity, though the mechanism remains unresolved. GmALA1 suppresses triacylglycerol accumulation while elevating lysophosphatidylethanolamine and lysophosphatidylcholine content in both wild-type and mutant yeast. These findings were consistent with GmALA1-driven remodeling of membrane lipid flux. In yeast and transgenic soybean hairy roots, GmALA1 alone or in combination with GmALIS2 differentially altered the internalization and tissue-specific distribution of multiple phospholipid classes, with the pattern of NBD-lipid accumulation differing depending on GmALIS2 co-expression and cellular context. GmALA1 expression was also associated with altered yeast sensitivity to divalent cations including Ca²⁺, Co²⁺, and Zn²⁺. Also, cellular cation accumulation in the P4-ATPase-deficient background was enhanced. However, whether this reflects a direct interaction between GmALA1 and cation homeostasis machinery remains to be established. These findings establish GmALA1 as a functionally active phospholipid flippase that coordinates transmembrane lipid redistribution in concert with GmALIS2. These findings advance our understanding of P4-ATPase biology in soybean and legume crops. Full article

Reservoir stimulation is essential in enhanced geothermal systems and unconventional reservoirs where low permeability, inadequate fracture connectivity, or near-wellbore damage restricts commercial injection or production. This review evaluates hydraulic fracturing, thermal stimulation, plasma-pulse stimulation, and selected dynamic stimulation technologies. It compares their physical mechanisms, fracture-network development, reservoir applications, permeability enhancement, operational maturity, deployment challenges, and future perspectives. Hydraulic fracturing remains the most mature method for reservoir-scale fracture creation, fracture conductivity, and reservoir connectivity. In enhanced geothermal systems, however, performance depends on the heat-exchange area, distributed flow, thermal sweep, long-term energy recovery, and induced-seismicity control rather than permeability enhancement alone. Thermal stimulation is integral to geothermal reservoir development. Cold-fluid injection generates thermoelastic stress redistribution, enlarges the fracture aperture, activates natural fractures, promotes thermally assisted fracture propagation, and influences thermal breakthrough. Plasma-pulse stimulation, also termed pulsed-power plasma, electrohydraulic, or shock-wave stimulation, provides a low-water method for near-wellbore permeability enhancement, damage bypass, fracture reactivation, and restimulation. Its broader deployment remains constrained by the limited treatment radius, scale-up uncertainty, energy-transfer efficiency, tool durability, completion integrity, and insufficient field validation. Liquid CO₂ phase-transition, propellant, and explosive stimulation provide additional dynamic-loading options with distinct fracture responses, controllability, safety, and technology readiness. Stimulation technologies should therefore be selected according to the dominant reservoir limitation and evaluated using sustained injectivity or productivity, effective reservoir contact, distributed flow, delayed thermal breakthrough, treatment durability, wellbore integrity, and a controlled geomechanical response. Future progress requires hybrid stimulation, coupled thermal–hydraulic–mechanical–chemical (THMC) modeling, integrated monitoring, adaptive control, physics-informed artificial intelligence, digital twins, standardized field validation, and techno-economic and life-cycle assessments. Full article

Modern agriculture faces increasing pressure from rising food demand, resource degradation, and biotic stress factors, highlighting the need for sustainable, non-chemical technologies. Cold atmospheric plasma (CAP) has emerged as a promising non-chemical seed-priming technology with potential applications in sustainable agriculture. The present study investigated the effects of dielectric barrier discharge (DBD)-generated CAP on seed germination and early seedling development in two Solanum lycopersicum genotypes (a common variety and an IdB hybrid) under controlled laboratory conditions. Seeds were exposed to CAP for 1, 2, 3, or 4 min, while untreated seeds served as controls. Early plant performance was evaluated after 47 days by determining germination rate, fresh biomass, dry biomass, and mineral biomass (ash content). CAP exposure duration significantly affected all gravimetric parameters in both genotypes. Among the tested treatments, 1 min exposure consistently produced the highest fresh, dry, and mineral biomass values, whereas longer exposure times (3–4 min) generally reduced seedling growth, indicating the transition from beneficial physiological stimulation to stress-induced inhibition. Despite the more pronounced response observed in the IdB hybrid, the statistical analysis demonstrated that treatment duration, rather than genotype, was the principal factor influencing biomass accumulation. The present results indicate that short-duration CAP treatment represents an effective seed-priming strategy for improving early tomato seedling development. Full article

Tomato spotted wilt disease, caused by Tomato spotted wilt virus (TSWV), poses a severe, widespread threat to commercial crop production. Triggering endogenous plant defense capacity serves as a promising tactic for sustainable disease control. Environmental factors, such as temperature, can modulate plant metabolic activities to suppress disease development. To characterize how sub-low temperatures shape tomato responses to TSWV, we maintained tomato seedlings under three regimens: room temperature (25 °C) and two sub-low temperatures (15 °C and 10 °C). Subsequent viral inoculation and phenotypic monitoring revealed that 15 °C pretreatment was associated with markedly reduced TSWV disease severity. RT-qPCR quantification further demonstrated that this 15 °C priming correlated with diminished accumulation of the viral NSs gene. Transcriptome profiling indicated that the 15 °C regime was linked to coordinated activation of cold acclimation pathways, hormone signaling cascades, and antiviral defense programs, which correlated with reduced TSWV accumulation. Specifically, 15 °C conditioning was correlated with the induction of a cold-responsive transcriptional network that overlaps with plant antiviral immune responses. This activated transcriptional signature is putatively associated with the stimulation of defensive cascades, maintenance of cellular homeostasis, and lowered viral accumulation, which collectively align with alleviated spotted wilt symptoms. To our knowledge, this work presents the first correlative evidence associating 15 °C sub-low temperature preconditioning with reduced TSWV accumulation in tomato. Collectively, these observations highlight the potential of temperature manipulation as a chemical-free disease mitigation approach and provide a valuable reference for sustainable crop protection strategies. Full article

The proliferation of daphnids in secondary clarifiers of urban wastewater treatment plants (WWTPs) can compromise effluent quality and disrupt treatment stability. This study evaluated the effectiveness of sodium hypochlorite (NaOCl) for controlling daphnid populations and assessed its influence on dormant eggs hatching. A pilot-scale oxidation ditch activated sludge system was operated under conditions simulating a full-scale WWTP. Acute toxicity tests were performed in clarified water (CW) and mixed liquor (ML) using NaOCl concentrations between 0.76 and 5 mg L⁻¹, with mortality monitored over 96 h and LC₅₀ values determined. In CW, concentrations ≥ 3.125 mg L⁻¹ caused 100% mortality within 24 h (24 h LC₅₀ = 1.75 mg L⁻¹). In ML, toxicity was significantly reduced (24 h LC₅₀ = 7.43 mg L⁻¹). Statistical analysis confirmed NaOCl concentration as the main driver of mortality, with additional contributions from operational parameters such as electrical conductivity, total dissolved solids, and dissolved oxygen. Hatching assays revealed that higher NaOCl concentrations and prior cold exposure (4 °C) increased ephippia hatching, reaching 40% under combined conditions. Although NaOCl effectively inhibits active organisms, it may stimulate dormant egg hatching, potentially sustaining populations. Optimized control strategies are therefore required to ensure effective and sustainable daphnid management in WWTPs. Full article

Osteoarthritis (OA) is a disabling joint disease characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Furthermore, catabolic inflammatory processes as well as dysregulated cellular signalling and oxidative stress are central to OA pathogenesis. Despite its growing global burden, currently available therapies primarily provide symptomatic relief and fail to target underlying molecular mechanisms and halt disease progression. Cold atmospheric plasma (CAP), a partially ionised, non-thermal gas that generates controlled reactive oxygen and nitrogen species (RONS), has emerged as a promising therapeutic modality capable of modulating redox-sensitive signalling pathways. CAP has demonstrated the capacity to suppress pro-inflammatory cytokine expression, enhance antioxidant defence mechanisms, influence macrophage polarisation, and stimulate tissue repair processes in rheumatoid arthritis, diabetic and dermal wound healing models. However, its potential as a disease-modifying therapy for the treatment of OA is not yet fully understood and warrants further experimental investigation. This review explores current pre-clinical evidence from different disease models, which may have implications for the potential application of CAP as a therapeutic intervention for OA, either as a disease-modifying therapy or as an adjuvant therapy for intra-articular drug delivery. Furthermore, key translational challenges including plasma parameter standardisation, interactions with synovial fluid and optimisation of joint-specific delivery strategies are discussed, identifying gaps that require further experimental investigation. Collectively, the findings of this review highlight CAP as a promising multimodal therapy with translational potential for the treatment of OA warranting further experimental validation and may open innovative avenues for future research. Full article

Background/Objectives: Lipid nanoparticles (LNPs) have emerged as crucial vehicles for messenger RNA (mRNA) applications in antitumor therapy. Combining LNPs with stimulator of interferon genes (STING) activation holds promise for treating “cold” tumors such as pancreatic cancer. However, two major challenges remain: inefficient mRNA escape from endosomes and STING pathway suppression in immunosuppressive tumor microenvironments. Methods: To improve endosomal escape, we developed a novel pH-responsive PEGylated lipid (Ben-mPEG₂₀₀₀) for mRNA-LNP preparation while using commercial Man-mPEG₂₀₀₀ for dendritic cell (DC)-targeted delivery of LNPs; to alleviate suppression of the STING pathway in the tumor microenvironment and activate immune responses, STING-R283S mRNA was encapsulated into LNPs, ultimately resulting in DC-targeted/pH-responsive LNPs loaded with STING-R283S mRNA for pancreatic cancer immunotherapy research. Results: After pH-responsive cleavage, Ben-mPEG₂₀₀₀ not only enhanced the positive charge of LNPs through the exposed protonated amino groups but also eliminated the PEG-induced steric hindrance effect. The combination of these two effects promoted membrane fusion between LNPs and the endosome, thereby enhancing mRNA translation. As a payload, STING-R283S could further amplify STING signaling in DCs without cytotoxicity to counteract immunosuppression in pancreatic cancer. Conclusions: This engineered LNP platform enhanced mRNA expression and STING activation in DCs, improving immunotherapy outcomes in pancreatic cancer. Full article