Search Results (774)

Phenylalanine ammonia-lyase (PAL) is the rate-limiting enzyme in the phenylpropane metabolic pathway, which is crucial for plant disease resistance. However, the functional roles of specific PAL members in lily defense against gray mold (Botrytis elliptica) remain unclear. Using the resistant lily cultivar ‘Sorbonne’, metabolomics analysis revealed that phenylpropane metabolites were significantly induced upon pathogen infection. Combined second- and third-generation transcriptome sequencing identified eight PAL family members. Among them, LhSorPAL1 and LhSorPAL2 were strongly induced by B. elliptica and were selected for further analysis. Both recombinant proteins exhibited PAL enzymatic activity catalyzing cinnamic acid production from L-phenylalanine. Overexpression of LhSorPAL1 or LhSorPAL2 in lily via Agrobacterium-mediated transformation had no obvious effect on plant growth but significantly increased the accumulation of lignin, flavonoids, and total phenols upon pathogen challenge, leading to enhanced resistance to gray mold. Conversely, antisense expression of LhSorPAL1 or LhSorPAL2 reduced the accumulation of these metabolites. Promoter analysis revealed that both LhSorPAL1pro and LhSorPAL2pro contain methyl jasmonate (MeJA)-, abscisic acid (ABA)-, and transcription factor-binding cis-elements. Collectively, these results demonstrate that LhSorPAL1 and LhSorPAL2 positively regulate lily resistance to B. elliptica by promoting phenylpropane metabolism, providing candidate genes for molecular breeding. Full article

As plant-based diets catalyze a global shift toward sustainable consumption, Chinese plant-based food firms are experiencing rapid growth and seeking to expand their international footprint. This study investigates the mechanisms underlying the internationalization performance of these firms by integrating the Technology–Organization–Environment (TOE) framework with a configurational perspective. We operationalize nine antecedents across three dimensions: the technological dimension (technological maturity, supply chain resilience, and digital transformation), the organizational dimension (food safety certification intensity, strategic partnership intensity, and talent acquisition intensity), and the environmental dimension (market adaptability, compliance and risk management, and product line breadth). Utilizing fuzzy-set qualitative comparative analysis (fsQCA) on a sample of N = 29 publicly listed Chinese plant-based firms, this research identifies three distinct equifinal pathways to superior internationalization performance. The first is the Collaboration-Compliance configuration (Organization–Environment-driven), which is primarily characterized by the synergy between strategic partnerships and regulatory risk management. The second is the Supply Chain-Compliance-Product Diversification configuration (Technology-Environment-driven), where international success is predicated on the interplay among supply chain resilience, institutional compliance, and product variety. The third is the Full-Factor Synergy configuration (Technology-Organization-Environment jointly driven), which emphasizes a holistic coupling of technological innovation, organizational coordination, and external institutional adaptation. By uncovering these complex causal mechanisms, this study moves beyond traditional linear analysis to reveal how diverse capability configurations can lead to equivalent internationalization outcomes. The findings provide actionable strategic guidance for firms navigating the global plant-based market and offer theoretical insights for policy frameworks supporting sustainable dietary transitions. Full article

The governing reaction–diffusion model for carbohydrate oxidation catalyzed by an immobilized bienzyme system glucose dehydrogenase and laccase within a spherical porous microreactor is adapted from Baronas et al. and extended here to the non-steady-state regime. The model consists of coupled non-linear partial differential equations based on non-Michaelis–Menten kinetics. The principal novelty of this work lies in the derivation of closed-form semi-analytical expressions for transient and steady-state concentrations of the carbohydrate substrate, oxygen, and product, as well as for the effectiveness factor, using the Laplace Homotopy Perturbation Method (LHPM). The LHPM solutions are validated against MATLAB R2026a numerical simulations (maximum error $<0.009\%$) and demonstrate superior accuracy compared to previously reported Adomian Decomposition Method (ADM) and Taylor Series Method (TSM) solutions. Parametric analysis reveals that the Thiele modulus, saturation parameters, and dimensionless time strongly influence the internal concentration profiles and reactor effectiveness. These analytical results provide rapid, closed-form predictive tools for optimizing catalyst particle size, enzyme loading, and operating conditions in immobilized enzyme microreactor systems. Full article

In recent years, the pivotal role of the gut microbiota and its metabolites in host health and disease has garnered increasing attention. Dietary phosphatidylcholine and choline are metabolized by gut bacteria to generate trimethylamine (TMA). Upon entering the bloodstream, TMA is oxidized by host liver enzymes to trimethylamine N-oxide (TMAO), a known independent risk factor for various systemic diseases, including atherosclerosis, thrombosis, and chronic kidney disease. Within this complex “diet–gut–host” metabolic axis, the microbial choline TMA-lyase (CutC) acts as the key rate-limiting enzyme that catalyzes the cleavage of choline to produce TMA. This review systematically summarizes the discovery history, enzymatic structural characteristics, and catalytic mechanism of CutC, highlighting its potential as a microbial metabolic target for treating associated diseases. By specifically analyzing existing inhibitor strategies and interventions, this article emphasizes the extensive potential of specific targeting of the CutC enzyme in precisely regulating the functions of the microecology. Full article

The change in learning methods to online/distance learning, catalyzed by recent health pandemics/social distancing requirements, has significantly changed how teaching occurs and what students experience in their learning spaces in regard to interference. New forms of interference exist, and they are related to the domestic setting of the student’s life. This study examined how factors of domestic life influence what students find in regard to interference in their online learning spaces through a Likert-scale defined answer process to a 29-question predictor variable inventory that also includes two outcome variables that address the amount of acoustic interference experienced in learning spaces. Moreover, through regression models and various applications of machine learning science, this research aims to reveal crucial indicators that influence student experiences regarding disturbances. In this respect, these findings highlight crucial roles that housing density and internal interactive actions within residential contexts have on disturbances. Furthermore, this research reveals critical understandings of perceptual inequalities present within distance learning student populations and indicates significant cultural and social consequences related to digital technologies. This is crucial, understood within foundational perspectives that are necessary to address psychosocial challenges and human–building interaction present within distance learning science and policies aimed at reducing noise. Full article

Greece is facing a wildfire crisis that parallels many other countries in fire-prone regions around the globe. Recent wildfire data for Greece point to an alarming trend of increasing fire size and severity catalyzed by climate change, lack of forest and fuel management, urban expansion into wildlands around major population centers, and rural exodus from areas that traditionally supported fire-resilient land uses. Fire management in Greece has long emphasized suppression with relatively little attention to prevention and coordination. In this paper, we identify key factors that are slowing progress towards a solution to the Greek wildfire crisis, including the current legislative framework around wildfire management that has contributed to conflicts and inefficiency. We then discuss specific policies to rebalance the current suppression emphasis by integrating new prevention strategies aiming to create fire-resilient landscapes and reduce wildfire impacts, widely adopt the use of technology, and enhance stakeholder cooperation for more efficient fire suppression. We also highlight how optimizing landscape scale management of fuels is contributing solutions to the wildfire crisis, specifically from the EU-funded FIRE-RES project. Full article

This study examines the Xinjiang Uygur Autonomous Region as a critical case study, constructing comprehensive evaluation frameworks for both ecological environment and tourism economy. We calculate the integrated development levels of both systems from 2010 to 2024, employing entropy weighting to derive composite development indices, Coupling Coordination Degree modeling to quantify the intensity and quality of system interactions, Relative Development Degree modeling to characterize coordination typologies and developmental asymmetries, and Grey Relational Analysis to identify key driving factors. Our findings reveal that although the coupling coordination of Xinjiang’s tourism–ecological system has transitioned from “mild imbalance” to “marginal coordination”, the system exhibits pronounced vulnerability and persistent “tourism-lag” dynamics. To effectively leverage the current “strategic window” of ecological surplus, we propose a multi-dimensional transformation pathway: (1) enhancing digital resilience through intelligent monitoring systems to mitigate external mobility shocks; (2) optimizing spatial connectivity via a “fast transit, slow travel” infrastructural paradigm; (3) institutionalizing micro-scale ecological governance to position oasis cities as sustainable “ecological gateways”; and (4) catalyzing deep cultural-tourism integration, shifting from scale-driven sightseeing to value-driven Silk Road heritage experiences. These pathways furnish a clear blueprint for Xinjiang to achieve high-quality, sustainable regional tourism development while maintaining its strategic positioning as a northwestern ecological security barrier. Full article

The effects of exchangeable cations on bisphenol A adsorption and degradation were investigated in montmorillonite-catalyzed ozonation and compared to the parent bentonite. Total BPA removal (100%) can be achieved after only 5 min adsorption on NaMt and by 15 min ozonation with all clay catalysts but without complete mineralization. The BPA degradation level was found to correlate to the ecotoxicity of the ozonized BPA mixtures, using the aquatic plant Lemna minor as a bioindicator species. Liquid chromatography revealed that BPA adsorption contributes to the ozonation process and that BPA degradation rates and ecotoxicity strongly depend on the exchangeable cation and the particle size of the clay catalyst. These factors also appear to govern the ozonation and adsorption process through catalyst dispersion in the liquid medium, with direct effects on the toxicity towards the living species. The results of the present work allow envisaging clay-based oxidative water treatments with advanced BPA removal that drastically reduce the amounts of persistent derivatives. Full article

As organizations globally pursue the twin transitions of digitalization and sustainability, whether digital tools inherently facilitate green objectives remains a critical debate. Drawing on Social Information Processing (SIP) theory, this study develops an affective–cognitive dual-path model, examining how perceived leader prosocial motivation catalyzes employees’ green innovation intention. Utilizing a mixed-methods design in China, we first conducted a scenario-based experiment (Study 1, N = 184) to establish internal validity, followed by a two-wave, multi-source field survey (Study 2, N = 428) across diverse industries to enhance ecological validity. Regression analyses confirm that perceived leader prosocial motivation positively relates to employees’ green innovation intentions. This relationship is mediated by green organizational identity and green mindfulness, underscoring the pivotal role of individual affective and cognitive factors in translating organizational green visions into employee innovation. Crucially, we reveal a critical signal interference effect: high workplace digitalization acts as a negative boundary condition that weakens the positive influence of leader motivation. Our findings highlight the necessity for leaders to cultivate and signal prosocial motivation to effectively inspire employees’ green innovation intentions. Furthermore, our study challenges the synergy myth of the twin transition. We provide critical insights for digital governance by revealing that excessive digital embedding can trigger cognitive overload and attention fragmentation among employees, ultimately stifling the organizational green transition. Full article

Epigenetics is a widely present mechanism for the modulation of gene expression without alterations in the underlying genetic sequence. Epigenetic signatures are significantly present in bacteria, with DNA methylation playing a key role in the modulation of bacterial physiology and pathogenesis. DNA methyltransferases (MTases) are the enzymes catalyzing the transfer of methyl groups to adenine or cytosine residues in the DNA using the methyl donor S-adenosyl-L-methionine (SAM). This process generates modified bases, N6-methyladenine (m6A), 5-methylcytosine (5mC), or N4-methyl cytosine (4mC) in the DNA, which influence fundamental cellular processes such as DNA transactions, DNA replication, transcription, and DNA repair. These MTases, earlier thought to be a part of primitive bacterial immune system, are now considered to be active players in gene regulation. They regulate bacterial adaptability to stress by virtue of phase variation and bistability. In pathogenic species such as Mycobacterium tuberculosis (Mtb), DNA methylation driven epigenetic reprogramming influences the expression of virulence factors, antibiotic tolerance, and persistence genes. This review gives a detailed account of role of DNA methyltransferases in bacterial epigenomics influencing various cellular processes. With the development of long-read high-throughput sequencing technologies, single-base mapping of bacterial methylomes has become possible. In the latter part of the review, we talk about these advances and the integration of synthetic biology to expand the potential of methylation systems for developing biosensors and switchable gene expression platforms. These strategies can be translated into future vaccine design and precision drugs for disease control. Deciphering bacterial DNA methylation can help gain insights into microbial evolution and design innovative therapeutics for various diseases. Full article

This systematic review examines the emerging interplay between ferroptosis and disulfidptosis, two distinct forms of regulated cell death (RCD) centered on the SLC7A11 (also known as xCT)-mediated metabolic paradox. Traditionally recognized as a potent anti-ferroptotic factor, SLC7A11 imports cystine for glutathione synthesis to neutralize iron-dependent lipid peroxidation. However, the discovery of disulfidptosis identifies SLC7A11 as a metabolic liability, representing a paradigm shift in our understanding of cellular antioxidant defense. This discovery reveals a transformative vulnerability in SLC7A11-overexpressing cells, shifting the focus from conventional survival mechanisms to the consequences of catastrophic structural collapse. Beyond metabolic exhaustion, this review highlights the role of metal dyshomeostasis as a primary driver, spanning from iron-catalyzed ferroptosis to copper-mediated metabolic interference. This conceptual framework redefines the SLC7A11 axis as a targetable “double-edged sword” in therapy-resistant malignancies. Clinical synthesis of multi-omic gene signatures, such as the disulfidptosis- and ferroptosis-related gene prognostic score (DRGPS) and the ferroptosis- and disulfidptosis-related gene (FDRG) scores, demonstrates their robust value in prognostic stratification and in predicting immunotherapy response across malignancies, including lung adenocarcinoma and hepatocellular carcinoma. Furthermore, we evaluate the capacity of disulfidptosis to prime immunogenic cell death (ICD) and remodel the immunosuppressive tumor microenvironment to bypass chemoresistance. By integrating mechanistic insights with clinical data, this review provides a comprehensive framework for targeting the SLC7A11 axis as a transformative therapeutic vulnerability in precision oncology. Full article

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that plays a crucial role in inflammation, immune responses, and tumor development. It was reported that TRAF6 primarily catalyzes K63-linked polyubiquitination to stabilize substrate proteins, thereby facilitating the malignant phenotype of tumors. Beyond its cytoplasmic roles, TRAF6 undergoes nuclear translocation in response to specific stimuli, where it interacts with chromatin modifiers. TRAF6 acts as a central mediator in key signaling pathways downstream of the Toll-like receptor, interleukin-1 receptor, and tumor necrosis factor receptor superfamilies, including NF-κB activation. TRAF6 exerts diverse oncogenic functions, including promoting cell proliferation, migration, metastasis, immune evasion, and therapy resistance. This involves modulating cellular pathways such as NF-κB and MAPK signaling, which contribute to malignant progression. Aberrant TRAF6 activation contributes to the pathogenesis of multiple malignancies, including colorectal cancer, melanoma, hepatocellular carcinoma, and acute myeloid leukemia, making it a promising therapeutic target for cancer treatment. This review summarizes the structural features, substrate diversity, and multifaceted roles of TRAF6 in cancer, as well as the development of TRAF6-targeting drugs and strategies. We hope this review can provide a comprehensive perspective on TRAF6-targeted therapeutic strategies for cancer. Full article

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α₁-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article

Background: Aberrant protein O-fucosylation mediated by protein O-fucosyltransferase 1 (POFUT1), has emerged as a hallmark of tumorigenesis that regulates key signaling pathways, including Notch, which is frequently dysregulated in cancers. Protein O-fucosylation, catalyzed by POFUT1, regulates Notch signaling and has been implicated in individual cancers, but its pan-cancer expression patterns, clinical significance, and relationship to tumor immunity remain incompletely characterized. Methodology: We conducted a multi-omics bioinformatics analysis using TCGA and other public datasets to evaluate POFUT1 expression across 33 cancer types (n > 10,000). Differential expressions, tumor stage correlations, and survival outcomes were assessed. Immune cell infiltration was estimated using SangerBox and TIMER algorithms, while promoter methylation patterns were analyzed through UALCAN. Functional enrichment and protein–protein interaction networks were constructed to elucidate functional mechanism. Western blot validation in prostate and ovarian cancer cell lines confirmed our computational analysis. Results: POFUT1 showed significant overexpression in 16 of 33 cancer types (FDR-adjusted p < 0.05), with the highest elevation in BRCA (breast invasive carcinoma; log2FC = 2.31) and LUAD (lung adenocarcinoma; log2FC = 2.1). A high POFUT1 expression correlated with poor overall survival in eight cancer types (HR range: 1.8–3.2, p < 0.01) and disease-free survival in seven cancers. POFUT1 levels positively correlated with myeloid-derived suppressor cells (MDSCs) infiltrating in 15 cancer types, while inversely correlated with natural killer T (NKT) cells presence in 15 cancers (mean R = −0.34, p < 0.05), indicating an association with immunosuppressive microenvironments. Promoter hypomethylation in tumors suggested epigenetic dysregulation as a potential driver of its overexpression. Western blot analysis confirmed POFUT1 protein upregulations in prostate and ovarian cancer cell lines (1.7–2.1-fold. p < 0.01), corroborating transcriptomic findings. Conclusion: This pan-cancer study establishes POFUT1 as a critical oncogenic factor linked to aggressive disease, immune evasion, and poor prognosis. Its consistent overexpression and functional impact highlight its potential as a biomarker and target for anticancer therapy. While these computational findings require experimental validation, POFUT1 emerges as a candidate biomarker warranting functional studies and potential therapeutic targeting. Full article

Background/Objectives: Resveratrol is a naturally occurring polyphenolic stilbene compound exhibiting a wide range of biological activities, and it has been extensively utilized as both a food additive and a pharmaceutical active ingredient. Typically, it can be directly extracted from natural sources such as grapes, mulberries, and peanuts, or obtained through catalytic hydrolysis of polydatin. To establish an efficient and optimized method for resveratrol production, we conducted a comprehensive study to refine the acid-catalyzed hydrolysis conditions of polydatin. Methods: A high-performance liquid chromatography method was developed for the quantitative determination of polydatin and resveratrol. To identify the optimal ranges of reaction temperature, HCl concentration, and ethanol concentration, single-factor experiments were conducted by evaluating their influences on hydrolysis kinetics and resveratrol yield. Based on these results, response surface methodology incorporating a Box–Behnken design was employed to optimize the hydrolysis process, using resveratrol yield as the response variable. Furthermore, time-course experiments were performed to determine the optimal reaction duration under the established optimal conditions. Results: Single-factor experiments demonstrated that increasing temperature and HCl concentration significantly accelerated hydrolysis, but resveratrol yield increased initially and then decreased with excessive increases in either factor. To further optimize the process, response surface methodology optimization experiments were conducted at temperatures of 60, 70, and 80 °C; HCl concentrations of 1.0, 1.5, and 2.0 M; and ethanol concentrations of 75%, 85%, and 95%. The optimal conditions were identified as follows: temperature, 70 °C; HCl concentration, 1.5 M; ethanol volume fraction 85%; and reaction time, 5 h. Under these conditions, the theoretical resveratrol yield was 85.68%, and the average yield from triplicate validation experiments was 86.01% (RSD = 0.56%), which was consistent with the theoretical value. Conclusions: The optimized acid-catalytic hydrolysis process using RSM is stable, feasible, and efficient, offering a promising approach for enhancing resveratrol production from polydatin. Full article