Search Results (180)

Exposure to heavy metals remains a significant public health concern due to their environmental persistence, bioaccumulation, and ability to interfere with essential cellular processes. A large part of metal-induced toxicity converges on the establishment of a chronic oxinflammatory state, driven by the reciprocal interaction between oxidative stress and inflammation. In this review, we synthesize current mechanistic evidence describing how toxic metals, including aluminum, arsenic, cadmium, lead, mercury, and nickel, disrupt redox homeostasis, impair cellular integrity, and activate inflammatory signaling pathways. These metals promote the excessive generation of reactive oxygen and nitrogen species through multiple mechanisms, including mitochondrial dysfunction, displacement of essential metal cofactors, and inhibition of antioxidant systems. The resulting molecular damage leads to the formation of damage-associated molecular patterns (DAMPs), which activate redox-sensitive transcription factors and inflammatory cascades. Importantly, emerging metabolomic evidence indicates that these processes are accompanied by coordinated metabolic reprogramming involving amino acid, lipid, and energy metabolism, as well as microbiota-derived metabolites. These metabolic alterations not only reflect cellular adaptation to stress but also actively contribute to the propagation of a systemic inflammatory state. An integrated oxinflammatory and metabolic response underlies structural and functional alterations across multiple organ systems, including the liver, kidneys, cardiovascular system, nervous system, and reproductive organs. Persistent exposure, even at low doses, sustains this often subclinical and chronic process, reinforcing the need to understand metabolic changes as central components of metal-induced toxicity. Full article

Reproductive barriers severely limit interspecific hybridization success among Hydrangea macrophylla, H. paniculata, and H. arborescens, thereby restricting the combination of ornamental traits and cold hardiness. We evaluated cross-compatibility, pollen tube growth, and embryo development in both direct and reciprocal crosses involving H. macrophylla with H. paniculata and H. arborescens. Both species pairs exhibited pronounced unilateral incompatibilities. When H. macrophylla served as the maternal parent, the percentages of seedling emergence were higher, whereas reciprocal crosses produced >84% ovary swelling but resulted in almost no seedlings. Fluorescence microscopy revealed mild prezygotic barriers in direct crosses but strong inhibition of pollen germination and pollen tube growth in reciprocal crosses. Paraffin section observations showed that postzygotic barriers were the primary cause of hybrid failure, with endosperm-type abortion predominating in direct crosses and embryo-type or complete abortion in reciprocal crosses. Consistent with these abortion patterns, direct crosses maintained higher proportions of normal embryos, whereas reciprocal crosses dropped below 10% at the globular stage and approached 0% at later stages. These findings support the use of timely embryo rescue for direct crosses and targeted mitigation of prezygotic barriers in reciprocal crosses to improve Hydrangea interspecific hybridization efficiency. Full article

The co-culture between Trametes sp. D and Aspergillus niger L14 resulted in a distinct orange-brown antagonistic band at their interface. Direct hyphal contact was associated with markedly enhanced production of numerous secondary metabolites (SMs), some of which were absent or decreased in monocultures. T. sp. D induced indolic compounds and cyclic dipeptides, such as Indole-3-acetamide and Cyclo-(Pro-Phe), whereas A. niger L14 overproduced polyketide-derived pigments and organic acids, such as Fonsecin and Kojic acid. These SMs did not inhibit their producer but suppressed the opponent’s growth, indicating reciprocal chemical antagonism. Transcriptomic analysis revealed upregulation of stress-related and metabolic genes, consistent with each fungus activating defense pathways. Biochemical assays showed that the confrontation zone had the highest oxidative stress markers, cell wall-degrading enzyme activity, and acidification (notably by A. niger L14), reflecting intense interfungal antagonism. The stress-response mitogen-activated protein kinase (MAPK) pathway was also activated in both fungi. Our findings supported a mechanistic model of fungal competition involving direct contact, chemical exchange, enzymatic attack, and stress signaling, highlighting that physical interactions likely contributed to triggering cryptic secondary metabolism and robust defense responses. Full article

Cannabis sativa is a multipurpose dioecious species whose crop performance is governed by sex expression. Although sex is genetically determined by an X/Y chromosome system, plants can develop flowers of the opposite sex through sex reversion, commonly induced by manipulating endogenous hormone levels using plant growth regulators (PGRs). Here, we evaluated the effectiveness of PGRs that promote or inhibit major hormone pathways implicated in plant sex expression. Male and female clones from two accessions were treated with foliar applications of nine PGRs and four combinatory treatments to assess sex- and genotype-specific responses. Floral biomass and the proportion of each sex were recorded at harvest to assess treatment effectiveness. Ethylene emerged as the primary regulator of chemically modulated sex reversion in C. sativa, with its inhibition by silver thiosulfate inducing strong female-to-male reversion and its promotion by ethephon inducing equally strong male-to-female reversion in the inflorescences. Gibberellin promotion on its own resulted in female-to-male reversion at the axial nodes only, while its inhibition showed no reciprocal effects. The combination of silver thiosulfate and gibberellic acid resulted in the most complete female-to-male reversion, and all sex-reverted flowers were fertile. Together, the results indicated that flowers at axial nodes and at the terminal ends of inflorescences are under different hormonal control. Cytokinins, auxins, and jasmonates were found to exert minimal influence on sex reversion. All treatments exhibited pleiotropic effects, particularly gibberellic acid and paclobutrazol, which altered resource allocation, shifting biomass away from and towards floral tissue, respectively. These findings advance our understanding of the hormonal regulation of sex expression in C. sativa and identify optimized approaches for its manipulation. Full article

Background/Objectives: Ganoderma lucidum (Curtis) P. Karst. (commonly known as reishi mushroom), a well-characterized medicinal fungus, contains diverse bioactive metabolites. This study aimed to fractionate, characterize and identify the biologically active inhibitors present in G. lucidum and to evaluate their antioxidant, antimicrobial, and antidiabetic activities. Methods: The ethanol extract of G. lucidum was fractionated using column chromatography, yielding ten distinct fractions (designated as A, B, E, F, K, L, M, N, O, and P based on their elution order and visual characteristics). Liquid Chromatography–Mass Spectrometry (LC-MS) analysis identified 46 bioactive compounds, including terpenoids, alkaloids, flavonoids, and polysaccharides. Results: Among the fractions, Fraction L exhibited the strongest antioxidant activity, with an IC₅₀ of 1.59 mg/mL. Fraction O displayed significant antibacterial activity against Escherichia coli ATCC 25922 (24.4 ± 0.238 mm), Klebsiella pneumoniae ATCC 13883 (20.5 ± 0.035 mm), Bacillus subtilis ATCC 6633 (8 ± 0.176 mm), and Staphylococcus warneri ATCC 10209 (20 ± 0.080 mm). Regarding antidiabetic activity, Fraction B demonstrated the strongest inhibition of α-amylase (IC₅₀ 1.69 ± 0.03 mg/mL), while Fraction E showed the strongest α-glucosidase inhibition (IC₅₀ = 1.69 ± 0.02 mg/mL), demonstrating reciprocal selectivity between enzyme targets. Conclusions: These results establish that chromatographic fractionation concentrates specific bioactivities into distinct fractions, supporting its potential for the development of novel therapeutic agents with enhanced specificity and efficacy. Full article

Background: The combination of conventional drugs and inhibitors of signaling molecules is an effective strategy to increase cancer treatment efficacy and reduce drug doses to protect against their cytotoxic effects. Our research has shown the cisplatin concentration-dependent shift in the role of MAP kinase JNK from antiapoptotic to proapoptotic in non-small cell lung cancer A549 cells. Cell death/survival signaling molecules, tumor suppressor p53 and pro-survival protein kinase AKT were detected to be differently regulated by JNK inhibition at low vs. high cisplatin concentrations. Here, we further investigated the phenomenon and potential mechanisms of combined JNK inhibition and cisplatin treatment. Methods: Cell death in vitro was evaluated by MTT and Western blot assays after combined cisplatin and specific inhibitor treatment; two-way ANOVA was used for analysis. Results: JNK is differently involved in determining cellular sensitivity to different DNA-damaging drugs. There is no universal cell death induction mechanism originating from DNA damage through the involvement of JNK. The outcome of JNK inhibition also depends on the cell type. We found that there is an unusual reciprocal interaction between p53 and AKT in cisplatin-treated A549 cells, where p53 inhibits AKT, while AKT activates p53. In the case of cisplatin + JNK inhibitor SP600125, DNA damage and reactive oxygen species (ROS) contribute to cell death regulation in different ways. ROS exert opposite roles on cell fate-determining molecules p53 and AKT, and ROS act on p53 and AKT in opposite directions at low vs. high concentrations of cisplatin, combined or not with JNK inhibition. The differentially activated p53 in response to ROS (at low versus high concentrations of cisplatin, combined with JNK inhibitor) may be a molecular switch in the role of JNK from antiapoptotic to neutral/proapoptotic, and an executor of cell death. ROS is a possible threshold regulator that, together with an as-yet-unidentified factor, can differentially regulate p53. As a result, AKT phosphorylation and function are altered. The findings emphasize the importance of assessing the role of drug concentration when combining them with JNK inhibition when monitoring therapeutic efficacy and toxicity issues in personalized cancer treatment. Full article

Hormone-independent breast and prostate cancers represent highly aggressive malignancies characterized by profound metabolic reprogramming, elevated oxidative stress, and loss of sensitivity to endocrine therapies. Increasing evidence indicates that tumor progression and metabolic plasticity are sustained by interconnected signaling networks linking transcriptional regulation to energy metabolism. Among these, the STAT3–PKM2–HIF-1α signaling axis, functionally reinforced by reactive oxygen species (ROS), has been proposed as a central regulator of the Warburg phenotype and cellular adaptation to adverse microenvironmental conditions. Using androgen-independent prostate cancer (DU145) and triple-negative breast cancer (KPL-4) cell lines, we demonstrated constitutive activation and reciprocal regulation of STAT3, PKM2, and HIF-1α. Pharmacological inhibition of STAT3, stabilization of tetrameric PKM2 by L-serine, and ROS scavenging with N-acetylcysteine significantly reduced STAT3 phosphorylation, PKM2 nuclear translocation, and HIF-1α stabilization. These molecular effects were accompanied by decreased intracellular ROS levels, reduced lactate production, increased pyruvate levels, and a metabolic shift toward oxidative phosphorylation. Functionally, treated cells exhibited reduced Ki-67 expression and impaired clonogenic capacity. Our results identify the STAT3–PKM2–HIF-1α/ROS axis as a key determinant of metabolic and phenotypic plasticity in hormone-independent breast and prostate cancers, highlighting its potential as a molecular target for therapeutic modulation of cancer-associated metabolic phenotypes. Full article

This study investigates the evolution of the structures of China’s domestic intercity tourism information flow networks, an increasingly important issue in an information-driven society. Moving beyond prior research that primarily emphasizes urban node attributes and multidimensional distances, this study applies social network analysis to develop an integrated analytical framework that incorporates endogenous structural effects, exogenous network effects, node attributes, and similarity effects. Using tourism information flows in China as an empirical proxy, the study examines the mechanisms underlying the formation and persistence of intercity relationships within the country. The results indicate that the self-organization of microscopic network structures plays a significant role in both tie formation and persistence, particularly through reciprocity, cyclicity, and convergence. Notably, the effect of cyclicity reversed during the COVID-19 pandemic and changed direction from relationship formation to persistence. In addition, cultural distance (proxied by dialect distance), geographical distance, and institutional distance significantly inhibit both the formation and persistence of intercity tourism information flows. Changes in urban node scale and node similarity also exert significant influences on network evolution. This study deepens the understanding of the spatial structural dynamics of China’s domestic intercity tourism information flows and provides a conceptual basis for future research on the evolutionary mechanisms of tourism network structures within a domestic context. Its direct significance lies in promoting sustainable urban tourism development, network resilience, and adaptive governance of urban systems. Full article

This study constructs a global transportation carbon emission spatial correlation network via a modified gravity model and explores its evolutionary characteristics and dynamic mechanisms by integrating three-dimensional evolutionary analysis (node, overall, structural) and temporal exponential random graph model (TERGM). The main findings are as follows: (1) Global transportation carbon emission spatial correlation intensity keeps rising, with improved connectivity and integration, forming three regionally agglomerated correlation poles centered on the United States (America), China (Asia) and major European countries (Europe). (2) Network centrality distributes asymmetrically: Switzerland, Norway and the United States remain core nodes, while China, Japan and other Asian economies with strong direct correlation radiation are not in the core tier. (3) Third, evolutionary dynamics stem from the synergistic interaction of multidimensional attributes. ① Economic level positively drives bidirectional connection emission and attraction; economic scale and openness curb emission but boost attraction, while tertiary industry structure inhibits both. ② Only economic level and government efficiency exert significant positive effects on absdiff, fostering network heterophilic attraction. ③ Spatial and institutional proximity in edgecov effectively facilitate connection formation. ④ Endogenous network variables present a collaborative mechanism of reciprocity and transmission, constrained by network density. ⑤ Temporal effects show early connection structure forms path dependence, resulting in low dynamic variability and overall network stability. Full article

Ectomycorrhizal (ECM) symbiosis is a fundamental mutualism crucial for forest eco-system health. Its establishment is governed by sophisticated molecular dialogue preceding physical colonization. This review synthesizes this pre-colonization crosstalk, beginning with reciprocal signal exchange where root exudates trigger fungal growth, and fungal lipochitooligosaccharides activate host symbiotic programming, often via the common symbiosis pathway. Successful colonization requires fungi to navigate plant immunity. They employ effectors, notably mycorrhiza-induced small secreted proteins (MiSSPs), to suppress defenses, e.g., by stabilizing jasmonate signaling repressors or inhibiting apoplastic proteases, establishing a localized “mycorrhiza-induced resistance.” Concurrent structural adaptations, including fungal hydrophobins, expansins, and cell wall-modifying enzymes like chitin deacetylase, facilitate adhesion and apoplastic penetration. While this sequential model integrates immune suppression with structural remodeling, current understanding is predominantly derived from a limited set of model systems. Significant knowledge gaps persist regarding species-specific determinants in non-model fungi and hosts, the influence of environmental variability and microbiome interactions, and methodological challenges in capturing early signaling in situ. This review’s main contributions are: providing a synthesized sequential model of molecular crosstalk; elucidating the dual fungal strategy of simultaneous immune suppression and structural remodeling; and identifying crucial knowledge gaps regarding non-model systems and species-specific determinants, establishing a research roadmap with implications for forest management and ecosystem sustainability. Full article

The Hedgehog (Hh) signaling pathway regulates key cellular processes, such as proliferation, differentiation, and morphogenesis. Although its canonical activation involves ligand binding to PTCH1, which activates Smoothened (SMO), noncanonical features of the pathway significantly contribute to cancer progression, particularly in prostate cancer (PCa). GLI3, a central transcription factor in the Hh pathway, can act as a repressor or activator depending on posttranslational modifications. In androgen-deprived PCa, GLI3 plays a critical role in driving castration-resistant phenotypes by interacting with the androgen receptor (AR), particularly the AR-V7 variant. This interaction enhances tumor survival and growth even under androgen deprivation therapy (ADT). Aberrant GLI3 activity is further driven by mutations in upstream regulators such as SPOP and MED12, which contribute to the progression of both prostate and other malignancies. Preclinical studies have shown promise in reducing tumor cell proliferation and migration, and in inducing apoptosis, by pharmacologically inhibiting the GLI3 pathway with SMO antagonists or GSK3β inhibitors. Recent evidence also highlights reciprocal interactions between Sonic Hedgehog (Shh) signaling and the AR that sustain tumor growth under ADT. GLI3 engagement with AR reinforces AR-dependent transcription, supporting tumor progression through noncanonical pathways. These findings suggest that targeting GLI3, particularly in combination with AR inhibition, could effectively overcome castration resistance and improve outcomes in patients with castration-resistant prostate cancer (CRPC). This review explores the role of GLI3 in both canonical and noncanonical Hh signaling, its potential as a therapeutic target, and future directions for overcoming resistance in Hh-driven cancers. Full article

Neurodegenerative diseases (NDDs), defined by the progressive loss of neurons, present a major challenge to global health. Oxidative stress and lysosomal dysfunction are both key pathogenic factors in NDDs, and they do not operate in isolation; instead, the vicious cycle they form, often mediated through organellar crosstalk, serves as the core driver of the pathological progression of NDDs, collectively worsening disease outcomes. Specifically, excessive reactive oxygen species (ROS) can disrupt lysosomal membrane integrity through lipid peroxidation and inhibit the activity of vacuolar ATPase (V-ATPase), ultimately leading to impaired lysosomal acidification. Meanwhile, lysosomal dysfunction hinders the clearance of damaged mitochondria (the primary endogenous source of ROS), toxic protein aggregates, and free iron ions. This further exacerbates ROS accumulation and accelerates neuronal degeneration. Conventional therapeutic approaches have limited efficacy, primarily due to the challenges in crossing the blood–brain barrier (BBB), insufficient targeting ability, and an inability to effectively intervene in this pathological loop. Nanotherapeutics, leveraging their tunable physicochemical properties and modular functional design, represent a transformative strategy to address these limitations. This review systematically elaborates on the reciprocal interplay between oxidative stress and lysosomal dysfunction in NDDs, with a particular focus on the central role of lysosome-mitochondria axis dysfunction, critically appraises recent advances in nanotechnology-based targeted therapies, and thereby provides a comprehensive theoretical framework to guide the development of novel NDD therapeutics. Full article

The Berberis nummularia fruit is rich in polyphenols and which are associated with the inhibition of carbohydrate-digesting enzymes. However, the phytochemical compositions, antioxidant strength, and the ability of the fruits on the inhibition of α-amylase to control postprandial blood glucose remained elusive. In this study, therefore, different concentrations of ethanol were used in ultrasound processing at 70 °C for 1 h to obtain the crude polyphenol of B. nummularia fruit (CPB) and obtain the purified polyphenol (PPB) using AB-8 macroporous resin. After this, the polyphenolic constituents within PPB were identified using LC-MS/QTOF and investigated for anti-hyperglycemic properties by sucrose loading test. The results showed that the optimal extraction yield (44.32 ± 2.08%) of CPB was achieved with 30% ethanol and the PPB from CPB was reached at 71.88 ± 2.74%. A total of 30 polyphenols including 13 phenolic acids, 13 flavonoids, 3 benzaldehyde derivatives, and 1 aromatic acid were identified, in which the caffeic acid had the highest content (426.20 ± 0.18 ng/mg). The PPB displayed potent α-amylase inhibitory activity with an IC₅₀ value of 69.91 μg/mL and kinetic analysis via Lineweaver–Burk double reciprocal plots confirmed a non-competitive inhibition mechanism. Moreover, at an administration dose of 100 mg/kg body weight (BW), PPB significantly reduced blood glucose levels by 13.75 ± 0.87% and exerted a marked ameliorative effect on postprandial hyperglycemia in vivo. Therefore, these findings provide a foundation for considering PPB as a beneficial functional food ingredient and a potential dietary supplement for the management of postprandial hyperglycemia. Full article

Single-cell RNA-sequencing has transformed our understanding of alveolar epithelial type 2 (AT2) cells and alveolar lipofibroblasts (LIFs) during lung injury and repair. Both cell types undergo dynamic transitions through intermediate states that determine whether the lung proceeds toward regeneration or fibrosis. Emerging evidence highlights reciprocal paracrine signaling between AT2/AT1 transitional cells and LIF-derived myofibroblasts (aMYFs) as a key regulatory axis. Among these, amphiregulin (AREG)–EGFR signaling functions as a central profibrotic pathway whose inhibition can restore alveolar differentiation and repair. The human WI-38 fibroblast model provides a practical platform to study the reversible LIF–MYF switch and screen antifibrotic and pro-regenerative compounds. Candidate therapeutics including metformin, haloperidol and FGF10 show promise in reprogramming fibroblast and epithelial states through metabolic and signaling modulation. Integrating WI-38-based assays, alveolosphere co-cultures, and multi-omics profiling offers a translational framework for identifying interventions that halt fibrosis and actively induce lung regeneration. This review highlights a unifying framework in which epithelial and mesenchymal plasticity converge to define repair outcomes and identifies actionable targets for promoting alveolar regeneration in chronic lung disease. Full article

This paper explores the café–gym symbiosis mode in Xi’an and its key influencing factors. Taking 63 sub-districts in the seven main urban districts of Xi’an as an example, based on the Dianping.com data of 753 cafés and 335 gyms and survey data from 492 questionnaires, this paper uses methods such as the symbiotic degree, symbiotic coefficient, and binary logistic regression model. On the basis of evaluating the symbiotic model between cafés and fitness centers, it explores the key factors influencing the symbiotic model of cafés and fitness centers. The results showed that cafés and gyms in Xi’an have a variety of characteristics, including agglomeration, correlation, complementarity, and combination, laying the foundation for a symbiosis between them. Among the subject symbiosis modes in Xi’an, point symbiosis was the main symbiotic organization mode. Simultaneously, the proportion of the point symbiosis mode was higher in the urban–rural transitional area than in other areas (traditional inner-city areas, mature built-up areas, emerging expansion areas). An asymmetric reciprocal symbiosis mode dominated the symbiotic behavior mode of entertainment industry objects in Xi’an. In terms of the total weekly entertainment consumer and the additional entertainment consumer dimensions, in the asymmetric reciprocal symbiosis mode, the proportion of cafés having a large impact on gyms was the highest: 60.00% and 62.86%, respectively. However, from the composite index dimension, in the asymmetric reciprocal symbiosis mode, the proportion of gyms having a large impact on cafés was the highest: 39.13%. From the symbiotic interface, the physical space within urban residential areas, office areas, commercial areas, and other main material spaces was the important basic support force for the symbiotic development of urban culture and the entertainment industry. The influence of the symbiosis mode of the culture and entertainment industry has stability. From the perspective of the symbiotic environment, cultural and creative elements, government policies, and consumer spending on entertainment foster the formation of an asymmetrical mutualistic symbiosis model between cafés and gyms. Conversely, factors such as marketization, globalization, and demographic factors inhibit its development. These findings offer valuable insights for urban planners and businesses, which help optimize the layout of the urban entertainment industry. Full article