Search Results (439)

Fine particulate matter (PM_2.5) poses a significant global environmental health threat and is closely associated with diseases across multiple organ systems. This review systematically summarizes the toxic effects and underlying mechanisms of PM_2.5 in the respiratory, cardiovascular, nervous, immune, endocrine, digestive, and genitourinary systems. Key pathogenic processes involve shared pathways such as oxidative stress, inflammatory responses, endoplasmic reticulum stress, autophagy, and apoptosis, along with the activation of system-specific signaling networks. The complex composition and notable spatiotemporal variability of PM_2.5 present challenges for assessing its health risks and clarifying its mechanisms. Moving forward, integrating multi-omics and molecular epidemiology approaches will be essential to unravel its multi-system pathogenic networks and support the development of effective intervention strategies. Full article

Saline–alkaline water constitutes a vital strategic non-traditional fishery resource in China, characterized by high pH values, elevated carbonate alkalinity, and complex ionic compositions. These extreme environmental conditions impose significant stress on aquatic animals, mainly by inducing ionic toxicity and disrupting acid–base regulatory mechanisms. Such disruptions subsequently lead to osmotic imbalance, metabolic dysregulation, and immunosuppression, thus restricting the survival and growth of aquatic species in aquaculture systems. Consequently, the sustainable development of the saline–alkaline aquaculture is imperative for enhancing production efficiency and promoting the utilization of marginal land and water resources. This review comprehensively summarizes the current status of saline–alkaline aquaculture and highlights the stress-inducing impacts of salinity, alkalinity, and specific ionic ratios on teleost fishes and crustaceans. It further explores key adaptive mechanisms, including osmoregulatory and ionoregulatory strategies, bioenergetic trade-offs related to oxygen consumption and ammonia excretion, coordinated antioxidant and innate immune responses, as well as recent findings from multi-omics research. This review aims to offer a scientific foundation for the selection and breeding of saline–alkaline-tolerant strains, the precise regulation of aquaculture water environments, and the development of ecological aquaculture models in saline–alkaline regions, thereby facilitating the sustainable utilization of saline–alkaline land and water resources. Full article

When using traditional approaches, such as pharmacokinetics and pharmacodynamics, the entire cellular or molecular response to drugs in the body cannot be fully ascertained or established. The oral medication process involves pharmacokinetics, followed by oral microbiomics and then gut microbiomics and pharmacodynamics. Recently, there has been increasing interest in the role of genetics (pharmacogenetics and pharmacogenomics) in both humans and microbiomes, as well as omics alterations (e.g., epigenetic, transcriptomic, proteomic, and metabolomic alterations as a consequence of drug exposure), which can help to ascertain the cellular responses to medications. Both the efficacy and toxicity of a drug are influenced by these factors. To assess these at an individual level, an integrative Personalized Medicine Model may be needed to help with medication management. Two example application cases for SSRIs and statins demonstrate the clinical usefulness of such a model, which can guide clinicians during drug selection and dosing to reduce reliance on trial-and-error, thus potentially improving patient outcomes and safety. Integrating this framework into practical clinical workflows requires the capture, analysis, and translation of multi-omics data in order to realize decision support protocols and actionable drug recommendations. This review also discusses IT requirements and different stakeholder roles. Although the proposed model can guide the treatment of diseases at the individual patient level, further research is still needed before it can be implemented as part of drug development research, clinical care, and healthcare delivery systems. Full article

The persistent discharge of refractory toxic organic pollutants poses a severe threat to aquatic environmental safety, driving the urgent demand for high-efficiency water treatment technologies in environmental engineering. Fenton and Fenton-like oxidation processes have garnered extensive attention due to their robust oxidizing capacity and environmental benignity; however, traditional Fenton systems are constrained by inherent limitations, including a narrow applicable pH range, potential secondary pollution, and cumbersome catalyst recovery. To address these challenges, Fenton-like catalysts have evolved progressively from single-metal systems to multi-metal alloy configurations. This review systematically elaborates on the fundamental principles and technical bottlenecks of classical Fenton and Fenton-like reactions, while comprehensively summarizing the research progress of multi-metal alloy catalysts—encompassing binary alloys, multi-component alloys, and high-entropy alloys. Special emphasis is placed on dissecting the core mechanisms through which multi-metal alloys optimize redox cycles and enhance structural stability, leveraging intermetallic synergistic effects, unique electronic structures, and lattice distortion. Furthermore, this work synthesizes key performance enhancement strategies for such catalysts, including co-catalyst synergy, external field assistance, and supported composite modification. Ultimately, this review aims to provide a scientific foundation and technical reference for the rational design, development, and engineering application of high-performance Fenton-like catalysts in sustainable wastewater remediation. 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

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine. Full article

Cys2/His2-type zinc finger transcription factors (C2H2 TFs) constitute one of the largest and most functionally diverse transcription factor families in plants, playing core regulatory roles in multiple aspects of plant growth, development, and stress adaptation. Based on literature data from databases including PubMed (1995–April 2026) and integrated with bioinformatics analyses, this review provides a comprehensive overview of this family. We first summarize the structural characteristics and classification systems of C2H2 TFs, and elucidate their evolutionary dynamics from lower plants to angiosperms. Regarding their impact on plant organ development, beyond key biological processes, this review details the molecular mechanisms of C2H2 TFs in floral organ morphogenesis (e.g., petal, sepal, stamen, and ovule development), pollen fertility maintenance, and flowering time regulation. Concurrently, we systematically analyze their functional pathways in responses to abiotic stresses (drought, high salinity, low temperature, aluminum toxicity, etc.) and biotic stresses (pathogens, pests), clarifying the molecular networks through which they coordinate reactive oxygen species (ROS) homeostasis, stomatal movement, and osmotic regulation by modulating hormone signaling pathways such as ABA, SA, and JA. Furthermore, this review discusses major limitations of current research, including knowledge gaps concerning functional redundancy, pseudogenization phenomena, and cell type-specific regulation. We also provide perspectives on future research directions leveraging cutting-edge technologies such as CRISPR gene editing, single-cell sequencing, and multi-omics integration, as well as their application prospects in crop stress resistance breeding and quality improvement. This review provides ideas for in-depth research on the regulatory network and related functions of C2H2 TFs, and offers reference value for improving plant traits, enhancing plant resistance, and increasing the production of plant secondary metabolites. Full article

Recent findings suggest that the gut microbiome significantly influences cancer outcomes, including responses to immune checkpoint inhibitor (ICI) treatments. Although early research focused on gut bacteria, it is now understood that the microbiome includes a bacteriome, virome, and mycobiome, all of which can modulate host immunity. Some commensal bacteria enhance anti-tumor immune responses and improve ICI efficacy, as demonstrated in both mice and patients. Fecal microbiota transplants (FMT) from patients responding to ICI have successfully reversed resistance in certain non-responders. In addition to bacteria, gut fungi and viruses are gaining attention as further factors influencing ICI effectiveness and toxicity. Recent multi-omics studies across cancer cohorts show that fungal and viral populations in the gut vary between ICI responders and non-responders. Commensal fungi may shape anti-cancer immunity by inducing inflammatory or tolerogenic pathways, while viral components can stimulate innate immune sensors that promote tumor surveillance. On the other hand, gut dysbiosis marked by expansion of pathobionts (including opportunistic fungi) and reduction in beneficial microbes is linked to serious immune-related adverse events (irAEs) such as ICI-induced colitis. This review discusses the multi-kingdom gut microbiome–bacteria, fungi, and viruses–and their interactions with the immune system in cancer therapy. We emphasize known mechanisms linking these microbes to anti-tumor immunity, overview human studies associating gut microbiome profiles with ICI outcomes and explore strategies to modulate the microbiome to enhance ICI efficacy while reducing toxicity. Understanding and utilizing the gut mycobiome and virome in conjunction with the bacteriome could pave the way for new biomarkers and therapeutic adjuvants in cancer immunotherapy. Full article

Microplastics (MPs) are increasingly recognized as a global environmental threat. Emerging evidence suggests they may have metabolic consequences. In this review, we synthesize current findings from animal and in vitro studies to propose a mechanistic framework linking MP exposure to type 2 diabetes mellitus (T2DM). This framework is uniquely centered on the gut–liver axis and macrophage-centric immune networks. We systematically delineate evidence suggesting that MPs can compromise intestinal barrier integrity, instigate gut dysbiosis, and promote pro-inflammatory M1 polarization of macrophages in experimental models. This immune activation is proposed to subsequently amplify hepatic inflammation, potentially contributing to systemic insulin resistance (IR) and pancreatic β-cell dysfunction. We emphasize that while this pathway is biologically plausible, direct causal evidence in humans remains limited and is a critical knowledge gap. Integrating multi-level evidence from animal models and in vitro systems, we delve into the trans-organ immunometabolic effects of MPs within adipose tissue, pancreas, and skeletal muscle, establishing their role as a novel class of “metabolic disruptors.” Critically, we assess the key controversies and knowledge gaps pertaining to dose–response relationships, particle-specific toxicity (size, polymer type, and additives), the effects of complex environmental mixtures, and the urgent need for robust human validation. We advocate for future research priorities, including multi-omics integration, advanced organ-on-a-chip platforms, prospective cohort studies, and targeted intervention strategies, to propel this field from mechanistic exploration toward clinical and public health relevance. Finally, this synthesis underscores that mitigating the production and environmental release of MPs, alongside developing strategies to impede their bioavailability and accumulation, represents a crucial public health imperative for the prevention of environment-related metabolic diseases. Full article

Bioretention systems are increasingly implemented as green infrastructure for urban stormwater management. However, their long-term performance is jeopardized by the continuous accumulation of potentially toxic metals in substrates and vegetation, posing significant risks to ecosystem health and human safety. Despite their growing application, the mechanisms driving metal dynamics and plant responses within these systems remain poorly understood. This study conducts a comprehensive multi-factor investigation into the accumulation, mobility, and biological impacts of four representative potentially toxic metals (Cd, Cu, Zn, and Pb) in bioretention soils and vegetation. Through controlled mesocosm experiments, we quantified metal concentrations in soils and three plant species, analyzed alterations in the physical and chemical properties of soil, and assessed plant physiological stress responses. Metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS), and statistical analyses were conducted using one-way ANOVA (p < 0.05). Cadmium exhibited the highest enrichment, with plant uptake increasing by 330.0% to 563.2%, especially in Iris tectorum Maxim., which demonstrated superior phytoaccumulation potential. Conversely, Ophiopogon japonicus Ker Gawl. showed remarkable tolerance to metal-induced stress, maintaining stable levels of chlorophyll content, photosynthetic rate, peroxidase activity, and soluble sugar concentration. Notably, the incorporation of humic substances significantly enhanced metal immobilization in soil, while simultaneously reducing plant uptake and physiological stress, revealing a promising strategy for toxicity mitigation. By integrating the effects of plant species, substrate composition, and influent concentration, this study provides novel insights into the complex interactions governing pollutant fate in bioretention systems. The findings offer critical guidance for optimizing bioretention design and management to ensure sustained pollutant removal efficiency and ecological resilience in urban stormwater treatment. Full article

Background: Frontotemporal dementia (FTD) is traditionally classified based on the accumulation of either tau or TDP-43 proteins; however, the presence of alpha-synuclein (α-Syn) in these patients is increasingly recognized as a critical factor driving disease progression. Methods: A comprehensive narrative review of recent clinical, neuropathological, and biochemical studies was conducted, focusing on cases of FTLD-synuclein and the occurrence of alpha-syn as a co-pathology in more common FTD variants. Results: Current evidence indicates that α-syn often co-aggregates with tau and TDP-43 via “cross-seeding” mechanisms, significantly accelerating neuronal loss and contributing to clinical heterogeneity. Although FTLD-synuclein is a rare, distinct subtype that mimics atypical multiple system atrophy, secondary α-syn pathology is common and strongly correlates with rapid cognitive decline. Furthermore, existing diagnostic biomarkers typically fail to detect this pathological overlap, which may explain the limited efficacy in protein-specific clinical trials. Conclusions: α-Syn is a major, yet under-recognized, catalyst of neurodegeneration within the FTD spectrum. The findings emphasize the need for future therapeutic and diagnostic strategies to adopt multi-target approaches, addressing the synergistic toxicity of multiple protein aggregates rather than isolating single protein in isolation. Full article

Psoriasis is a chronic immune-mediated skin disease with highly variable responses to systemic therapies. Emerging evidence highlights the microbiome as a potential modulator of drug efficacy and toxicity. Gut bacteria can enzymatically metabolize drugs, such as methotrexate, altering bioavailability and therapeutic outcomes, while microbial metabolites—including short-chain fatty acids, branched-chain amino acids, and tryptophan derivatives—shape host immunity and barrier integrity, influencing drug action. Baseline microbial signatures have been linked to treatment response, potentially predicting anti-TNF or IL-17 inhibitor efficacy. Systemic therapies themselves reshape microbial communities: IL-17 blockade induces broad shifts in gut and skin microbiota, whereas cyclosporine and anti-TNF agents exert subtler effects. Small molecules such as apremilast and fumarates may reduce fungal overgrowth and influence microbial composition, whereas data on JAK/TYK2 inhibitors remain limited. Notably, current evidence exhibits a literature bias toward the gut microbiota, while the roles of the oral and skin axes remain understudied. Adjunctive microbiome-directed interventions, including probiotics and fecal microbiota transplantation, have demonstrated potential to enhance treatment outcomes by promoting anti-inflammatory taxa and restoring barrier function. Despite these promising findings, current evidence is heterogeneous, often limited by small sample sizes, short follow-up, and variable methodology. Integrating pharmacomicrobiomics data with clinical, genetic, and multi-omics profiling could enable precision medicine approaches in psoriasis, allowing therapy selection tailored to individual microbial and metabolic signatures. Future research should focus on longitudinal, multicenter studies to identify actionable microbial biomarkers, clarify mechanistic interactions between drugs, microbes, and host immunity, and evaluate microbiome-targeted adjuncts in randomized trials. Understanding the bidirectional crosstalk between systemic therapies and the microbiome may transform psoriasis management, improving efficacy, reducing adverse events, and enabling durable, personalized responses. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease that imposes substantial physical, emotional, and socioeconomic burdens on patients. Conventional therapeutic approaches are often limited by systemic toxicity, inadequate joint targeting, and variable patient responses, highlighting the urgent need for advanced drug delivery systems. Smart hydrogels have emerged as a promising platform for RA treatment due to their unique three-dimensional hydrophilic networks, excellent biocompatibility, and tunable physicochemical properties. This review systematically summarizes the preparation strategies and design principles of smart hydrogels, with an emphasis on chemically and physically crosslinked networks as well as composite systems. It further outlines the major stimulus-responsive release mechanisms—including temperature, pH, reactive oxygen species (ROS), light, and enzyme triggers—that enable targeted and controlled drug delivery within the inflamed joint microenvironment. Among the various types discussed, temperature-responsive and multi-responsive hydrogels are most frequently investigated for their potential to achieve localized, on-demand therapy. Despite considerable preclinical progress, the clinical translation of smart hydrogels faces critical challenges, including insufficient long-term biocompatibility data, lack of standardized evaluation protocols, and difficulties in scalable manufacturing. This review aims to provide a conceptual framework for the rational design of smart hydrogels and to stimulate interdisciplinary efforts toward overcoming existing translational barriers in RA treatment. Full article

Accelerated industrialization has caused complex mixed toxicant pollution, where synergistic or antagonistic interactions render conventional detection methods inadequate. Herein, we develop an integrated framework by pioneering the integration of microbial electrochemical systems (MECs) with machine learning (ML) for quantifying formaldehyde, tetracycline, Ag⁺, and Cu²⁺ in multi-component, multi-ratio, and multi-concentration mixtures. MECs generated dynamic current–time (I–t) signals responsive to toxicant stress, though signal overlap from mixed toxicants hindered direct quantification. Guided by toxicokinetics and electrochemical mechanisms, we developed a novel mechanism-driven feature engineering strategy with exclusively original indicators, which extracted 22 multidimensional features capturing instantaneous characteristics, kinetic patterns, and microbial stress-adaptive responses to resolve signal ambiguity, and provided biologically meaningful, high-information feature inputs that effectively bridge electrochemical response signals and ML modeling. Comparative analysis of four ML models (SVM, KNN, PLS, and RF) showed RF outperformed others, achieving R² > 0.9 for all toxicants (formaldehyde: 0.959; tetracycline: 0.934; Ag⁺: 0.936; Cu²⁺: 0.957) with minimized MAE and RMSE. Microbial community analysis identified Geobacter anodireducens (71.5%, electroactive for heavy metals) and Comamonas testosteroni (12.9%, organic degrader) as key functional taxa, supported by KEGG enzyme abundance data. This work overcomes traditional MEC limitations via innovative feature engineering and pioneering ML integration, providing a rapid, low-cost, and high-accuracy tool for environmental mixed toxicant monitoring. Full article

Pesticides are widely used in rice cultivation for pest control to guarantee crop productivity. Intensive use of these chemicals causes harmful effects on rice plants, such as physiological and biochemical stress responses. Such stress is often expressed as oxidative damage, disruption of metabolic balance, and a reduction in plant resilience to environmental challenges. In recent years, omic technologies (such as transcriptomics, epigenomics, proteomics, and metabolomics) have contributed to identifying molecular pathways affected by pesticide exposure. However, no comprehensive synthesis of rice-specific omic evidence currently exists, limiting translational applications. These omic studies revealed activation of detoxification-related enzymes and transporters, alongside changes in antioxidant defenses, hormone-mediated signaling, and membrane remodeling. This review presents current omic-based approaches used to investigate pesticide-induced stress in rice. It focuses on molecular responses including changes in gene expression, enzymatic detoxification, metabolic reprogramming, and stress signaling pathways. The review also highlights how multi-omic integration can contribute to a more holistic understanding of these stress responses, combining cross-layer evidence that connects gene regulation, protein activity, and metabolic remodeling. Despite these advancements, there are still challenges, particularly in the interpretation of complex datasets, the integration of multiple omic layers and the translation of results to real agricultural conditions. Finally, the review also discusses biotechnological approaches that may improve rice tolerance to pesticide exposure. In summary, the role of omic approaches to elucidate pesticide toxicity in rice and to contribute to more resilient crop production systems is critically reviewed. Full article