Search Results (466)

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even when these asparagus plants are replaced with new ones, the new plants remain unproductive (asparagus replant problem). The main causes of these problems are a Fusarium infection and asparagus autotoxicity. Several reviews have been conducted on Fusarium. Despite the accumulation of evidence on asparagus autotoxicity in the literature over the past four decades, no review has focused specifically on asparagus autotoxicity. It has been reported that asparagus growth is inhibited by asparagus root residues, leachates, root exudates, and rhizosphere soils. Several phenylpropanoids, including trans-cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, have been identified as asparagus autotoxic substances in these root residues, root exudates, rhizosphere soils, growth media, and/or plant tissues. Tryptophan, 3,4-methylenedioxycinnamic acid, and iso-agatharesinol were also identified as asparagus autotoxic substances. These substances may cause autotoxicity by disrupting phytohormone levels, cellular metabolism, impairing membrane function, and by inducing oxidative stress. Although cinnamic, p-coumaric, caffeic, and ferulic acids have been reported to act as antibiotics, these compounds have also been shown to weaken the defense mechanisms of asparagus against pathogen infection, and enhance the Fusarium pathogenicity. The presence of these autotoxic substances, coupled with a Fusarium infection, may create a vicious cycle that worsens “asparagus decline” and “asparagus replant problem”. This is the first review to focus on the asparagus autotoxicity. Full article

The stability of subsea tunnels is governed by the strong coupling among stress redistribution, damage evolution, and seepage flow (Stress–Damage–Seepage, SDS). The dynamic interplay, especially under high water pressure, often leads to catastrophic failures, yet its mechanisms, particularly the role of support timing, remain insufficiently understood due to limitations in conventional numerical methods. This study aims to unravel the SDS coupling mechanisms during tunnel excavation under high hydraulic head, and to quantitatively investigate how support timing influences the stability of the surrounding rock within this coupled system. A coupled Computational Fluid Dynamics and Discrete Element Method (CFD-DEM) framework was employed. In this approach, excavation-induced damage, crack propagation, and fluid–particle interactions are explicitly resolved at the particle scale, whereas the macroscopic permeability evolution is captured through an imposed empirical exponential relationship. Simulations were conducted under both steady-state and transient seepage conditions with varying stress ratios and water heads. High-head transient seepage intensifies SDS coupling, dynamically redistributing seepage forces to damage zone edges and amplifying damage. Support timing critically mediates this interaction: premature support risks tensile failure at the tunnel periphery, while delayed support allows a vicious cycle of shear failure and increased inflow. Optimal “timely” support, applied after initial deformation, diverts high seepage forces inward, minimizing final damage. The spatiotemporal synchronization of transient seepage forces with damage evolution is pivotal for stability. Support timing acts as a key control variable. The CFD-DEM framework effectively elucidates these micro-mechanisms, providing a scientific basis for the dynamic design of support in high-pressure subsea tunnels. Full article

Heart failure (HF) with reduced ejection fraction is a systemic disorder that extends beyond cardiac dysfunction and involves peripheral organs, particularly skeletal muscle. Exercise intolerance and fatigue are the hallmark manifestations of HF that strongly predict morbidity and mortality. Accumulating evidence suggests that intrinsic skeletal muscle abnormalities are key contributors to exercise intolerance in HF. In HF, skeletal muscle undergoes metabolic remodeling characterized by shifts in fiber type composition, mitochondrial dysfunction, and increased oxidative stress. Mitochondrial dysfunction, characterized by decreased mitochondrial density, impaired biogenesis, and reduced respiratory capacity, further compromises skeletal muscle performance. These alterations impair adenosine triphosphate (ATP) generation via oxidative phosphorylation, forcing reliance on less efficient anaerobic glycolysis. The resulting metabolic shift exacerbates early lactate accumulation, muscle fatigue, and diminished exercise capacity. In parallel, an increase in oxidative and carbonyl stress, along with a decrease in antioxidant defenses as well as derangements in pathways that remove toxic lipid peroxidation, heightens oxidative and carbonyl stress perpetuating injury and establishing a vicious cycle of progressive muscle dysfunction. Thus, metabolic remodeling in skeletal muscle represents a central determinant of exercise intolerance in HF. While exercise training remains the most effective strategy to restore skeletal muscle health and exercise tolerance, emerging therapies offer novel avenues for intervention. Future research should focus on elucidating the molecular mechanisms underlying skeletal muscle dysfunction and developing therapies that restore metabolic integrity and functional capacity in HF. Full article

Photo-oxidative stress, resulting from an imbalance between light absorption and photosynthetic carbon utilization, poses a fundamental challenge to plant survival and productivity. This review synthesizes recent advances to present an integrated framework connecting reactive oxygen species (ROS) signaling, damage propagation, and systems-level resilience. We move beyond describing ROS as mere toxic byproducts to position them as central hubs in a complex, interconnected network. We integrate the specific sites of ROS generation, particularly ¹O₂ at PSII and H₂O₂ at PSI, with their distinct retrograde signaling pathways (e.g., EXECUTER, β-cyclocitral, and RES/RCS pathways) that reprogram nuclear gene expression. A systems perspective is then applied to reveal how initial photochemical damage propagates through a self-amplifying “vicious cycle” of impaired photosystem repair, lipid peroxidation, and protein oxidation, ultimately threatening cellular integrity. Counteracting this cycle is a multi-layered photoprotective arsenal including NPQ, alternative electron sinks (CEF, WWC), and an integrated antioxidant network, which we re-evaluate not as independent modules but as a coordinated, evolutionary-tuned defense system. We synthesize this knowledge to highlight a central paradigm for crop improvement: the pervasive growth–defense trade-off. Investment in photoprotection, while crucial for survival, diverts resources from yield, explaining why single-gene modifications often fail in the field. Therefore, we argue that future strategies must move beyond simply enhancing single components and instead focus on “optimizing the network”. We conclude by outlining how synthetic biology, multi-omics integration, and genomics-assisted breeding can be leveraged to fine-tune this integrated system, aiming to develop climate-resilient crops that balance productivity with survival in an increasingly volatile climate. Full article

Postharvest autolysis severely compromises the commercial value of fresh Dictyophora rubrovolvata. This study integrated physiological, ultrastructural, and metabolomic analyses to elucidate the underlying mechanism. Results indicated a continuous decline in cellular adenosine triphosphate levels during storage, leading to an energy crisis and triggering cellular stress responses. Metabolomic analysis revealed that the fruiting bodies activate pathways such as glycolysis and the pentose phosphate pathway through metabolic reprogramming to maintain homeostasis. However, the intensifying energy crisis inhibited Calcium ion ATPase activity, disrupting ion homeostasis and leading to Ca²⁺ influx. This activated phospholipases and initiated membrane lipid degradation, accompanied by a burst of reactive oxygen species and elevated levels of H₂O₂ and malondialdehyde, creating a vicious cycle of oxidative stress. Concurrently, cell wall components (chitin, β-1,3-glucan, cellulose) are accelerated in degradation due to the upregulation of corresponding hydrolases. Transmission electron microscopy confirmed progressive disintegration of cellular structures, including mitochondria, the plasma membrane, and the cell wall. These findings establish an “energy-membrane lipid-cell wall” cascade framework, revealing that D. rubrovolvata autolysis is an active, orderly form of programmed cell death under energy stress. This study provides new insights into the physiological mechanisms of postharvest quality deterioration in edible fungi. Full article

Both gut microbiota dysbiosis and disrupted cholesterol metabolism are associated with colorectal cancer (CRC). While the interactions between these two factors have been well explored in diseases such as cardiovascular disease and atherosclerosis, their interactions and underlying mechanisms in CRC pathogenesis remain insufficiently explored, constituting a critical area for further investigation. This review examines the complex relationship between gut microbiota and cholesterol metabolism in CRC development from 2 perspectives: how specific gut microbial species can increase CRC risk by modulating cholesterol metabolism, particularly through bile acids and oxysterols, and how disrupted cholesterol metabolism can exacerbate microbial dysbiosis and promote CRC. The bidirectional relationship between gut dysbiosis and cholesterol dysregulation creates a vicious cycle that drives CRC development. Moreover, the potential of targeting the gut microbiome and cholesterol metabolism to develop new strategies for preventing and treating CRC is discussed, highlighting the promise of certain bacterial strains that exert protective effects via cholesterol-lowering mechanisms. By elucidating the intricate connections between gut microbiota, cholesterol metabolism, and CRC, this review paves the way for innovative approaches in CRC prevention and therapy. Full article

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus that contributes substantially to chronic kidney failure and increased cardiovascular risk. Beyond progressive deterioration of renal function, DKD is associated with disturbances in endocrine and vascular regulation. Among these, alterations in vitamin D homeostasis and blood pressure (BP) control represent clinically relevant, yet incompletely integrated aspects of DKD pathophysiology. This narrative review synthesizes current evidence on the multidirectional relationships between DKD, vitamin D deficiency, and arterial hypertension (AH). Attention is given to renal mechanisms responsible for reduced vitamin D availability in DKD, including proteinuria-related loss of vitamin D-binding proteins, impaired proximal tubular reabsorption, decreased renal activation of vitamin D, and hormonal regulators such as fibroblast growth factor-23. It further discusses how insufficient vitamin D signaling may influence renal and vascular pathways involved in BP regulation. Mechanistic links between vitamin D deficiency and AH in DKD are discussed, with emphasis on maladaptive activation of the renin–angiotensin–aldosterone system (RAAS), persistent inflammation, oxidative stress, endothelial dysfunction, and insulin resistance. These interdependent processes promote both renal injury progression and sustained elevations in BP, forming a self-reinforcing pathogenic loop. Finally, available data on vitamin D-based therapeutic strategies in DKD are reviewed, including native vitamin D supplementation, active vitamin D metabolites, and vitamin D receptor agonists. Although experimental and observational studies suggest potential nephroprotective and vasculoprotective effects, evidence from randomized clinical trials remains heterogeneous. Further well-designed prospective studies are required to clarify the clinical utility of vitamin D interventions in patients with DKD and coexisting AH. Full article

Taxifolin, a natural flavonoid, consistently exerts cytoprotective effects against various oxidative stresses. In this study, we systematically evaluated its photoprotective efficacy and underlying mechanisms against ultraviolet B (UVB)-induced injury in human immortalized keratinocytes (HaCaT). Cell viability and apoptosis were assessed by MTT, fluorescence staining, and flow cytometry, while integrative transcriptomic and proteomic analyses were employed to identify core pathways and key mediators. Taxifolin exhibited antioxidant capacity comparable to that of ascorbic acid under identical in vitro radical-scavenging assays. Moreover, it displayed a strong absorption peak at 289 nm that overlaps the UVB spectrum (280–320 nm), enabling it to act as a chemical sunscreen. In UVB-challenged HaCaT cells, taxifolin markedly reduced intracellular reactive oxygen species (ROS) and attenuated JNK/p38 MAPK activation, as evidenced by Western blot, thereby breaking the ROS-MAPK vicious cycle. Multi-omics revealed that taxifolin was associated with attenuation of UVB-imposed G1/S arrest concomitant with restored Cyclin expression, while up-regulating MYC, FOXQ1, HMOX1 and AP-1 components c-Jun/c-Fos and thereby switching on a pro-survival transcriptional program. Consequently, apoptosis was suppressed and survival was significantly improved. Collectively, taxifolin integrated chemical filtration, ROS scavenging and signaling modulation to support a multi-target photoprotective network, which provides mechanistic insight into taxifolin-mediated cytoprotection and identifies candidate molecular nodes for further validation. Full article

Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article

In 2023, the terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) was proposed. MASLD uses metabolic abnormalities as an inclusion criterion. On the other hand, sarcopenia is defined by decrease in muscle mass and muscle strength. Skeletal muscle can be affected by insulin resistance (IR), and it is the largest site of insulin-stimulated glucose disposal. In recent years, advances in treatment have extended the life expectancy of patients with chronic liver disease (CLD). Due to the aging population, aging-related primary sarcopenia is expected to increase. On the other hand, liver fibrosis is an important treatment target associated with the onset of serious adverse events and poor prognosis in MASLD. The liver is the central organ for nutrition and metabolism, and patients with CLD may develop secondary sarcopenia due to various nutritional and metabolic disorders unrelated to aging. There is a strong correlation between sarcopenia, muscle fatty degeneration, liver fibrosis and IR in MASLD. MASLD and sarcopenia have a bidirectional relationship, forming a vicious cycle. In this review, we will summarize the relationship between MASLD and sarcopenia based on the current knowledge. Full article

Purpose of Review—sleep disturbance is the main complaint associated with patients who suffer acute postoperative pain. Sleep disturbance may also increase the pain sensitivity and contribute to the development and maintenance of chronic pain. The pathophysiology of pain is complex; management of perioperative pain and preventing chronic pain are challenges in clinical. Use of opioids for pain management are still a therapeutic mainstay and generally safe when taken, in a short time, for severe postoperative pain relief. For long-term use tolerance may be developed, and for their euphoric property, addiction, overdose incidents, and even death may be the social problems. Therefore, the opioid-sparing multimodal analgesia (MMA) for pain management is recommended in current postoperative pain management. The successful MMA for pain management will enhance patient recovery after surgery with less chronic CPSP and long-term opioid use disorder (OUD). The present review discusses all currently used analgesics actions and interactions, and opioid-sparing or opioid-free analgesia in perioperative pain management. Acute pain following major trauma or surgery may originate from both nociceptive and neuropathic mechanisms. Approximately 10–50% of surgical patients develop chronic postoperative pain, which not only causes persistent discomfort but also leads to functional limitations and psychological distress. Growing evidence highlights a close and bidirectional relationship between sleep and pain: pain disrupts sleep architecture, while sleep deprivation intensifies pain sensitivity and impairs recovery. This reciprocal interaction forms a vicious cycle that poses challenges for effective pain management. Melatonin—a neurohormone secreted by the pineal gland—plays a crucial role in regulating circadian rhythm and sleep–wake cycles. Beyond its chronobiotic action, melatonin exhibits anti-nociceptive, anti-inflammatory, and opioid-sparing properties. Recent preclinical studies have demonstrated that exogenous melatonin can attenuate nociceptive responses to noxious stimuli and enhance morphine analgesia while attenuating morphine tolerance. Moreover, environmental light manipulation preserving the circadian rhythm has been shown to synergistically maintain melatonin secretion, improve sleep quality, and modulate neuroimmune responses involved in pain regulation. Together, these findings suggest that circadian alignment and melatonin supplementation may represent a promising integrative approach for improving both pain control and sleep health in perioperative and chronic pain conditions. Chronic pain patients frequently experience opioid tolerance during long-term therapy, resulting in diminished analgesic efficacy and a need for escalating doses. Our recent work revealed that constant light exposure suppresses endogenous melatonin, heightens pro-inflammatory cytokines (TNF-α, IL-1β), reduces IL-10, and accelerates morphine tolerance in a neuropathic pain model. In contrast, maintaining circadian light–dark cycles or supplementing melatonin preserves melatonin rhythm, reduces glial activation, and sustains morphine antinociception. Melatonin’s co-administration not only attenuates morphine tolerance but also enhances morphine efficacy through the modulation of inflammatory and glial pathways. These findings underscore melatonin’s multifaceted role as both a chronotherapeutic and neuroprotective agent, integrating circadian regulation with pain modulation. Clinically, the application of melatonin or circadian-aligned strategies could guide personalized pain and sleep management, offering safer and more effective multimodal analgesic protocols with reduced opioid dependence and improved quality of life. Full article

Coercion theory posits that a vicious cycle of negative reinforcement traps both parents and children, shaping young children to become stably aggressive in conflicts with their parents. Research on intimate partner violence has found some evidence supporting the application of coercion theory in explaining aggressive escalation in adult conflicts as well. It is unclear whether the same processes are at play during teens’ early dating relationships. On the one hand, dating aggression emerges as soon as dating relationships do. On the other hand, we also know that if aggression presents extremely early in relationships, dissolution is the most likely path. We explored the role of coercion in 209 teen dating couples who were observed in a laboratory series of problem-solving discussions and analogue conflict tasks. All data were coded by trained coders blind to hypotheses. Analyses suggest that the negative reinforcement of hostility is indeed significantly associated with both psychological and physical aggression in an adolescent dating sample. Implications for prevention and intervention are discussed, as well as developmental processes that may contribute to dating aggression in light of our findings. Full article

Objective: To address the heavy burden of ego depletion and decision conflict in patients with advanced cancer, this study employed network analysis to explore their interaction mechanisms and identify key intervention targets, overcoming the limitations of traditional linear studies. Methods: A total of 200 patients with advanced cancer were assessed using the Self-Regulatory Fatigue Scale (SRFS), Decisional Conflict Scale (DCS), and Functional Assessment of Cancer Therapy-General (FACT-G). A Gaussian Graphical Model (GGM) was constructed to identify key nodes. Results: Network analysis revealed a tight interactive network among ego depletion, decision conflict, and quality of life. Emotional Function (F3) and Emotional Fatigue (SF2) formed a core emotional cluster, while Uncertainty (D1) was the key cognitive hub. The core nodes F3, D1, and Social/Family Function (F2) were identified as crucial regulators connecting different modules. The core node with the highest Expected Influence was F4 (Functional Status, EI = 0.523), and the key bridge node connecting different modules was F2 (Social/Family Function, bridge strength = 1.114). D3 (Effective Decision-Making, EI = −0.469) was identified as a negative key node associated with adverse network effects. Quantitatively, the core nodes of the network were F4 (Functional Status, EI = 0.523), SF3 (Behavioral Fatigue, EI = 0.353), and SF1 (Cognitive Fatigue, EI = 0.326); the bridge nodes were F2 (Social/Family Function, bridge strength = 1.114), SF2 (Emotional Fatigue, bridge strength = 0.966), and D1 (Uncertainty, bridge strength = 0.858); and D3 (Effective Decision-Making, EI = −0.469) was the negative key node. Conclusions: This study challenges the traditional “symptom-specific treatment” model and proposes a new paradigm of “node-targeted intervention.” Qualitatively, this study clarifies the multidimensional interactive mechanism of ego depletion, decision conflict, and quality of life in advanced cancer patients, and identifies key intervention nodes with different functional attributes (core nodes, bridge nodes, negative nodes). It provides empirical evidence for developing targeted palliative care strategies, which may offer new insights for optimizing symptom management in this population. Clinical Relevance: This study highlights the importance of exploring the multidimensional interaction mechanisms between self-regulatory fatigue, decision conflict, and quality of life in advanced cancer patients, emphasizing the guiding role of core nodes (Functional Status, Behavioral Fatigue, Cognitive Fatigue), bridge nodes (Social/Family Function, Emotional Fatigue, Uncertainty), and the negative node (Effective Decision-Making) in precise intervention. The findings support the integration of node-targeted hierarchical interventions into routine palliative care for advanced cancer patients to break the symptom vicious cycle and enhance their quality of life. Full article

The human microbiome plays a crucial role in health, being involved in both physiological and pathological processes. The highly dynamic microbiome composition is shaped by different factors, which also may affect host–microbe interactions. Although this relationship is complex and incompletely understood, the interplay between the microbiome, oxidative stress and inflammation is increasingly recognized. Microbial metabolites and specific probiotic strains contribute to maintaining redox homeostasis through multiple pathways, such as regulating the immune system and inflammatory processes or influencing mitochondrial reactive oxygen species production and antioxidant signaling pathways. Oxidative stress and inflammation, in turn, may affect the microbiome by altering microbial diversity and function. These disturbances are believed to create a vicious cycle that further disrupts homeostasis and promotes the appearance of different diseases. This review synthesizes current evidence on the interplay between the microbiome, oxidative stress, and inflammation, highlighting its relevance to both physiological and pathological states. Full article

Skin aging commonly manifests as deepening wrinkles, loss of elasticity, and weakened barrier function, resulting from the long-term accumulation of multiple biological processes. Dermal fibroblasts, as the primary source of extracellular matrix, not only provide structural support but also play an active role in aging. On one hand, they undergo intrinsic aging due to telomere shortening, mitochondrial decline, and dysregulation of signaling pathways (e.g., TGF-β, mTOR). On the other hand, they release inflammatory cytokines and proteases via the senescence-associated secretory pattern (SASP), disrupting keratinocyte function, melanin distribution, immune surveillance, and even microvascular and adipose tissue functions. This destabilizes the matrix equilibrium and exacerbates inflammation, creating a vicious cycle. While strategies like dasatinib/quercetin, rapamycin, or retinol show promise, they remain constrained by transdermal efficiency and targeting limitations. This review aims to elucidate these mechanisms and interactions, providing insights for developing more effective anti-aging interventions. Full article