Search Results (811)

Environmental NH₃ is a major pollutant in intensive livestock production, but its effects on host-associated microbiota remain insufficiently characterized. This systematic review evaluated the impact of environmental NH₃ exposure on the respiratory and gastrointestinal microbiome of poultry, swine, and cattle. Following PRISMA 2020 guidelines, PubMed, Web of Science, and Scopus were searched, identifying 175 records. After duplicate removal and screening, eight studies were included: five in broiler chickens and three in pigs, while no eligible bovine studies were identified. NH₃ exposure was associated with alterations in microbial diversity and composition, accompanied by epithelial injury, inflammatory activation, oxidative stress, and impaired production outcomes. Evidence was strongest in broilers, where both respiratory and gastrointestinal microbial communities were affected. In pigs, gastrointestinal microbiome and metabolic alterations were demonstrated, whereas evidence for respiratory microbiome involvement was more limited. Microbiota depletion and transplantation experiments in broilers further indicated that intestinal dysbiosis may contribute to respiratory injury through TLR4/MyD88/NF-κB signaling, supporting a potential gut–lung interaction. Overall, environmental NH₃ represents an important ecological stressor affecting livestock microbiota, although standardized longitudinal and mechanistic studies, particularly in pigs and cattle, are needed to establish causality and species-specific responses. Full article

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of ASD. The microbiota–gut–brain axis (MGBA), a critical pathway mediating crosstalk between the gut microbiota and the brain, has been extensively documented to be deeply involved in the pathological progression of ASD in recent years. However, prior studies have predominantly focused on the unidirectional regulation of the brain by gut microbiota, lacking an integrated account of the bidirectional regulation across immune, metabolic, and endocrine systems. Centered on the immune–metabolic–endocrine interactive network, this review systematically delineates the bidirectional regulatory mechanisms of the MGBA in ASD by integrating recent evidence from microbiota sequencing, animal models, and clinical intervention studies, with the aim of clarifying the bidirectional causal controversy between intestinal microecological disturbance and ASD behavioral abnormalities. This review proposes that in children with ASD, decreased abundance of beneficial intestinal bacteria and disrupted metabolic profiles of short-chain fatty acids synergistically impair intestinal barrier integrity, triggering peripheral chronic inflammation that further drives excessive microglial activation-mediated central neuroinflammation. Subsequently, disturbances in the homeostasis of multiple neurotransmitters including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), histamine, and dopamine occur via the vagus nerve and hypothalamic–pituitary–adrenal (HPA) axis, ultimately driving ASD behavioral abnormalities. Conversely, chronic stress and behavioral characteristics associated with ASD reshape the intestinal microecology through neuroendocrine pathways, forming a vicious cycle of “microbiota dysbiosis—immune inflammation—HPA axis hyperactivity—further intestinal microecological imbalance”. This review summarizes the therapeutic efficacy and translational bottlenecks of three types of microecological interventions: fecal microbiota transplantation (FMT), probiotics, and ketogenic diet, and analyzes the current limitations in the field, including pronounced population heterogeneity, unclear cross-talk mechanisms among multiple pathways, and the scarcity of large-sample clinical evidence. Collectively, this review preliminarily elucidates the complete multi-system interactive framework of MGBA regulation in ASD, providing theoretical support for mechanistic research and gut-targeted individualized interventions for ASD. Full article

Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a critical model for investigating clonal dynamics, as hematopoietic reconstitution occurs amidst significant proliferative stress and immune-mediated pressures. This study utilized longitudinal next-generation sequencing of a 30-gene panel to track clonal evolution in 20 patients and their matched-related or haploidentical donors. The findings revealed that post-transplant hematopoiesis is frequently driven by donor-derived clones, with DNMT3A being the most prevalent mutation in the study population. A key finding was the significant association between the presence of the donor TET2 Leu1721Trp variant and reduced overall survival in recipients (median 14.3 months compared with 50.8 months for wild type; p = 0.0100). Additionally, the study showed that the re-emergence of recipient-derived clones, particularly oncogenic DNMT3A mutations, frequently preceded graft failure or disease relapse. These findings suggest that, although donor clonal hematopoiesis is generally considered clinically neutral, specific genetic variants can profoundly influence clinical outcomes, suggesting that comprehensive molecular screening of donors and longitudinal molecular monitoring of recipients may be essential to optimize transplant outcomes and personalize post-HSCT management. Full article

Acute kidney injury (AKI) is a common critical syndrome with high morbidity and mortality, and a subset of patients may progress to chronic kidney disease. Recent studies have revealed that gut microbiota and their metabolites play pivotal roles in the pathogenesis of AKI. Under AKI conditions, the gut microbiota composition undergoes significant alterations, characterized by decreased beneficial bacteria and expansion of opportunistic pathogens, accompanied by impaired intestinal barrier and disordered microbial metabolism. Gut microbiota metabolites can be classified into protective metabolites (short-chain fatty acids, secondary bile acids, tryptophan metabolites, D-amino acids, and polyamines) and toxic metabolites (indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and endotoxin). The former exert renoprotective effects through anti-inflammatory, antioxidant, and barrier-maintaining mechanisms, while the latter aggravate kidney injury via oxidative stress, inflammation activation, and hemodynamic disturbance. Based on the gut–kidney axis theory, interventions targeting gut microbiota (probiotics, prebiotics, fecal microbiota transplantation) and those targeting metabolites (supplementation of protective metabolites, removal of toxic metabolites) have shown promising prospects. This narrative review summarizes the characteristics of gut microbiota changes, classification and function of key metabolites, core mechanisms driving AKI, and microbiota-based intervention strategies, aiming to provide novel insights for early recognition and precision prevention of AKI. Full article

The current challenges associated with the conservation and restoration of plant biodiversity make it necessary to test new biotechnological approaches. Optimizing the stages of clonal micropropagation using synthetic growth biostimulants—protatranes (1,2,3)—enables the targeted modification of physiological processes in plants. This increases their stress resistance, stimulates development, and reduces the cost of the final product. In this paper, the stimulating effect of the protatran (1), which we have named “crezacin”, on the processes of in vitro rooting and acclimatization to ex vitro conditions in microplants of the rare wild species Lilium pensylvanicum Ker Gawl was studied. No effect of crezacin and α-naphthylacetic acid on the development and growth of the microbulb during the rooting stage was detected. Crezacin at a concentration of 1.0 mg/L inhibited root elongation, but did not affect root number. Using α-naphthylacetic acid at a concentration of 0.93 mg/L was ineffective in inducing in vitro rhizogenesis. The survival rate of regenerated plants cultivated on media supplemented with crezacin was found to be 100%. The positive effect of crezacin on the content of photosynthetic pigments in the leaves of regenerated plants was also demonstrated. The addition of ultra-low concentrations (0.001–0.1 mg/L) of crezacin increased pigment content by up to 1.5 times (p < 0.05) compared to the control group. The increase in chlorophyll and carotenoid levels upon the addition of crezacin to the culture medium significantly facilitated the transition from a heterotrophic to an autotrophic mode of nutrition when microplants were transplanted into a soil substrate. Further research on clonal micropropagation of rare plant species and horticultural crops will be conducted using protatranes 2 and 3. Full article

Ischemia–reperfusion injury (IRI) is a common form of tissue injury encountered in myocardial infarction, ischemic stroke, solid-organ transplantation, and complex vascular surgery. Timely restoration of blood flow is essential for salvaging ischemic tissues; however, reperfusion itself can induce sterile inflammation and oxidative stress, further compromising microvascular and organ function. Accumulating evidence indicates that alterations in the local microenvironment associated with innate immune responses contribute to this pathological process, with neutrophils representing among the earliest effector cells recruited to injured tissues. In response to danger signals such as damage-associated molecular patterns, neutrophils can release neutrophil extracellular traps (NETs), extracellular web-like structures composed of decondensed chromatin and granular proteins. Extracellular NETs can injure endothelial and parenchymal cells and provide procoagulant scaffolds that contribute to immunothrombosis and local inflammatory responses. Current evidence is derived predominantly from clinical samples and experimental models across different organs. Owing to organ-specific differences in microvascular architecture, cellular composition, and ischemia–reperfusion conditions, the triggers, relative pathological contributions, and responses to NET-targeted interventions are not uniform across tissues. This review first summarizes the intracellular events preceding NET release, the molecular composition of extracellular NETs, and the mechanisms of NET extrusion. We then provide an organ-based synthesis of the local triggers, major injurious effects, and interventional evidence for NETs in the heart, liver, lung, kidney, brain, intestine, limb, and skin, while discussing recurrent pathological features—including microthrombosis, endothelial or barrier injury, and inflammatory amplification—in the context of organ-specific differences and the limitations of the available evidence. In addition, we evaluate therapeutic strategies involving degradation of extracellular NETs and neutralization of their toxic components, inhibition of NET-associated enzymes and upstream signaling pathways, and spatiotemporally targeted delivery, together with the major barriers to clinical translation. Overall, this review provides an organ-structured synthesis of current evidence linking NETs to IRI and offers a framework for understanding their context-dependent pathological roles and for developing organ- and phase-specific therapeutic strategies. Full article

Lichen transplantation can reveal spatial variation in biological responses across urban environments, but visible vitality cannot identify specific pollutants. We transplanted the epiphytic lichen Hypogymnia physodes from a presumed lower-impact forest area to 20 sites in Jelgava, Latvia and assessed its visible condition monthly for 243 days. The primary endpoint was first-observed necrosis; discoloration was retained as a descriptive secondary state. Thirteen primary transplants developed necrosis, first detected between days 62 and 215. One transplant was right-censored at day 123 after pruning, and six had no observed necrosis by day 243. Kaplan–Meier analysis gave a median time to first-observed necrosis of 184 days (20 primary transplants; 13 events; and 7 censored). A descriptive Urban Stress Index summarized event timing for 19 sites with complete follow-up. Correlations between this index and land-use proportions were statistically non-significant. Exploratory correlations with co-located winter snow Pb and Zn concentrations were negative, contrary to a simple metal-toxicity interpretation. The observed necrosis may reflect altered environmental conditions after transplantation rather than metal accumulation; absent concurrent air and thallus chemistry, microcli-mate measurements, and site replication, pollutant-source attribution is precluded. The approach is therefore best used for exploratory spatial screening and hypothesis generation. Full article

The fact that the population is getting older has greatly increased the occurrence of cognitive decline and neurodegenerative diseases, underlining the importance of having reliable biomarkers that can measure biological aging before irreversible neurological damage takes place. New evidence shows that brain aging is not just the result of changes within neurons themselves but is also greatly affected by the gut microbiota via immune, metabolic, endocrine, and neurovascular signaling. This review brings together the existing knowledge about biomarkers of biological aging-such as telomere shortening, epigenetic clocks, oxidative stress, inflammation, cellular senescence, and metabolic dysfunction-as well as established cognitive biomarkers obtained from neuroimaging, cerebrospinal fluid, blood, genetic evaluations, and neuropsychological tests. We also point out that changes associated with age in the composition of the gut microbiota and the metabolites it produces are becoming more and more involved in the mechanisms connecting intestinal dysbiosis, dysfunction of the blood-brain barrier (BBB), neuroinflammation, and age-related cognitive decline. Through this approach of combined and complementary biomarker systems, we hypothesize that the gut microbiota has emerged as a central regulator of biological and cognitive aging and may provide a useful source for development of biomarkers of cognitive resilience and risk of neurodegenerative diseases. Lastly, we consider microbiome-based interventions, including probiotics, prebiotics, dietary changes, fecal microbial transplant, and new treatment modalities derived from molecular studies, as possible approaches to the prevention and management of age-related cognitive decline. Collectively, this review provides a comprehensive framework linking aging biology, microbiome science, and cognitive biomarkers to advance biomarker-driven precision medicine for healthy brain aging. Full article

Hepatic ischemia–reperfusion injury (IRI) is a major clinical challenge in liver surgery and transplantation, contributing to postoperative complications and graft dysfunction. The pathogenesis of hepatic IRI is complex and multifactorial, involving ischemia-induced metabolic consequences, oxidative stress, inflammatory responses, endothelial dysfunction, and the activation of immune pathways upon reperfusion. Despite extensive research efforts, the translation of preclinical findings into effective clinical interventions remains limited. This review provides a critical overview of the principal models used to investigate hepatic IRI. Conventional two-dimensional in vitro systems, including monoculture and co-culture models, offer controlled environments for mechanistic studies and high-throughput screening, but fail to fully reproduce the structural and cellular complexity of the liver microenvironment. Animal models, particularly those based on mice, rats, and pigs, remain essential for studying the systemic and multicellular aspects of hepatic IRI. Nevertheless, species-specific physiological differences, ethical concerns, high costs, and limited translational predictability represent significant limitations. In this context, three-dimensional liver models have emerged as promising alternatives capable of bridging the gap between in vitro systems and animal experimentation. By more accurately recapitulating tissue architecture, cell–cell interactions, and functional heterogeneity, 3D platforms offer enhanced physiological relevance and translational potential. We discuss the strengths and limitations of each experimental approach and highlight the role of advanced 3D models as complementary tools that may enable more accurate investigations of hepatic IRI and accelerate the development of effective therapeutic strategies. Full article

Bell peppers (Capsicum annuum L.) are of great importance and have high productive potential in Brazil, especially in the Northeast region; however, their production is limited due to salinity problems in water and soil. The objective of this study was to evaluate sources and methods of calcium application for mitigating salt stress in bell pepper plants grown in a substrate-based hydroponic system. The experiment was conducted using a split-plot design in a 2 × 2 × 3 layout with four replicates, consisting of two application methods (substrate and spray), two ECiw levels (0.5 and 5.0 dS m⁻¹), and three calcium sources (no calcium—NCa; calcium nitrate—Ca(NO₃)₂; calcium complexed with amino acids—Ca-AA). Forty-two days after transplanting, gas exchange analysis, chlorophyll a, b, and total chlorophyll indices, chlorophyll fluorescence, fruit number and weight, and yield per plant were measured. Ca-AA showed higher photosystem II efficiency when applied via the substrate and higher stomatal conductance (28.10%), resulted in higher fruit yield compared to the other treatments, and contributed to a reduction in apical rot. Meanwhile, the application of Ca(NO₃)₂ improved electron transport in photosystem II by 5.46%, gas exchange, and increased chlorophyll b and total chlorophyll indices by 29.62% and 10.93%, respectively. It is concluded that the application of Ca sources, especially Ca-AA, has the potential to mitigate the effects of salt stress on bell pepper plants in a substrate-based hydroponic system, improving their photosynthetic and productive performance. Full article

The selection and breeding of salt-tolerant rice and the use of saline–alkali land for rice cultivation are crucial for food security. However, most studies have focused only on the seedling salt tolerance stage, with little research on the salt tolerance mechanisms during the reproductive growth period. This study selected the salt-tolerant rice line SR17, the salt-tolerant variety SR86, and the salt-sensitive variety IR29 as research subjects. Two salt stress gradients of 0% and 0.5% (7.8 dS m⁻¹) were established. Salt stress was applied continuously from rice transplanting to the maturity stage, and the differences in response mechanisms during the young panicle stage under long-term salt stress were analyzed. The results showed that, under salt stress, SR17 exhibited the least lipid peroxidation and membrane damage, followed by SR86, while IR29 suffered the most severe damage. SR17 and SR86 could reduce oxidative damage and maintain membrane system integrity by activating the antioxidant enzyme system and accumulating soluble proteins. In contrast, the antioxidant system in IR29 was insufficiently activated; this indicates that the adaptability of this variety to salt-induced oxidative stress is relatively poor. The chlorophyll content and most photosynthetic parameters in SR17 showed no significant changes, and leaf gas exchange performance and chlorophyll status were the least affected, whereas IR29 suffered severe damage. Agronomic trait investigation revealed that, compared with the control, SR17 exhibited the smallest reductions in plant height, spikelets per panicle, 1000-grain weight, grain yield per plant, and main spikelet number under salt stress, and the decreases in key yield-related indicators—effective panicle number, grain yield per plant, and seed setting rate—were not significant. This study confirms that SR17 possesses superior salt tolerance and holds potential for further breeding and multi-environment trials, while also providing an important basis for elucidating the physiological mechanisms of salt tolerance during the reproductive stage of rice. Full article

Heart failure (HF) is a systemic syndrome in which prognosis depends on cardiac dysfunction, congestion, cardiorenal and cardiohepatic interactions, inflammation, and metabolic dysregulation. The liver is exposed to elevated systemic venous pressure and reduced forward flow, and contributes to albumin and coagulation factor synthesis, bile acid metabolism, iron homeostasis, and the acute-phase response. Cardiohepatic injury involves hemodynamic stress, sinusoidal endothelial dysfunction, oxidative stress, inflammatory signaling, fibrogenesis, and altered metabolic regulation. Congestive hepatopathy is associated with right-sided HF, tricuspid regurgitation (TR), pulmonary hypertension, and elevated central venous pressure, whereas hypoxic hepatitis develops during low-output states, shock, or acute circulatory deterioration. These mechanisms may coexist, producing congestive/cholestatic, hypoperfusive/ischemic and mixed/systemic reserve profiles. Composite liver-related scores, including Model for End-Stage Liver Disease (MELD), MELD excluding International Normalized Ratio (MELD-XI), MELD with sodium (MELD-Na), MELD-Albumin and albumin–bilirubin (ALBI) score, may reflect congestion, hepatorenal dysfunction, nutritional status and reduced systemic reserve. This review summarizes hemodynamic and molecular mechanisms of cardiohepatic injury, liver-related biomarkers and composite scores, with emphases on advanced HF, left ventricular assist device (LVAD) therapy and heart transplantation. Liver-related abnormalities remain underrecognized in HF. Their serial interpretation may support risk stratification, but composite scores should complement rather than replace comprehensive clinical assessment. Full article

Background: Climate change-driven heat stress (HS) poses a growing threat to pregnancy outcomes; however, the mechanisms linking maternal HS to fetal growth restriction (FGR) remain incompletely understood, and effective nutritional interventions are lacking. The gut–placenta axis critically governs maternal–fetal health, but its role in mediating HS-related FGR has yet to be elucidated. Methods: A murine model of gestational HS (38.5 °C, 2.5 h daily from E0.5 to E12.5) was established to investigate the protective effects of chlorogenic acid (CGA) on HS-induced FGR. Placental efficiency, oxidative status, barrier integrity, and intestinal permeability were assessed. Gut microbiota composition was profiled by 16S rRNA sequencing, while tight junction protein expression in the placenta and intestine was evaluated by Western blot. Additionally, antibiotic-induced microbiota reduction and fecal microbiota transplantation (FMT) were performed to explore the role of gut microbiota in alleviating HS. Results: HS exposure significantly reduced fetal weight without altering litter size, accompanied by reduced placental efficiency and proportion of the labyrinth zone relative to the total placental area. HS triggered oxidative stress and downregulated tight junction proteins (Claudin-1, Occludin) in both the placenta and intestine, indicating compromised barrier integrity. CGA treatment robustly reversed these abnormalities and restored placental structure. In the gut, CGA prevented HS-induced intestinal barrier dysfunction and selectively reshaped the microbiota, enhancing the Firmicutes/Bacteroidetes ratio and promoting beneficial Lactobacillus lineages. Notably, under antibiotic-induced microbial reduction, FMT from CGA-treated donors effectively alleviated HS-induced fetal growth restriction. Conclusions: In summary, our study suggests that gestational HS exposure may trigger FGR through the gut–placenta axis. CGA effectively reverses FGR by restoring placental efficiency and placental barrier integrity, while alleviating maternal gut dysbiosis and intestinal barrier impairment. FMT experiments further confirm that the gut microbiota may play a key role in this protection. Collectively, these findings suggest that targeting the gut–placenta axis with CGA may offer a practical nutritional strategy to mitigate HS-triggered adverse pregnancy outcomes. Full article

Background and Objectives: Endothelial dysfunction is increasingly recognized as a key determinant of transplant outcomes. The Endothelial Activation and Stress Index (EASIX), originally validated in allogeneic stem cell transplantation, integrates markers of endothelial stress into a single composite score. Its prognostic role in autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains undefined. We evaluated the pre-transplant prognostic value of EASIX, an albumin-modified formulation (mEASIX_alb), and nutritional indices (Prognostic Nutritional Index [PNI] and Controlling Nutritional Status [CONUT] score) in a large MM-ASCT cohort. Materials and Methods: We retrospectively analyzed 274 MM patients who underwent ASCT at a single institution. The pre-ASCT EASIX (LDH × Creatinine/Platelets), mEASIX_alb (LDH × Creatinine/[Platelets × Albumin]), PNI (10 × Albumin [g/dL] + 0.005 × Lymphocyte count), and CONUT score were calculated from laboratory values obtained on day 3. Optimal binary cutoffs were determined by maximally selected rank statistics. Overall survival (OS) and progression-free survival (PFS) were analyzed with Cox models in which EASIX and mEASIX_alb were entered as continuous, log-transformed variables; binary cutoffs were used only for descriptive Kaplan–Meier illustration. Internal model validity was assessed by bootstrap resampling (B = 1000). Results: Over a median follow-up of 81.3 months, 150 patients (54.7%) died, and 207 (75.5%) experienced disease progression or death. Using illustrative cutoffs (EASIX > 0.471, mEASIX_alb > 0.208, PNI < 52.29), higher EASIX was associated with shorter OS (66.7 vs. 108.1 months; p = 0.012) and PFS (27.4 vs. 42.7 months; p = 0.018). In multivariable analysis, log-transformed EASIX (HR 1.40, 95% CI 1.10–1.77; p = 0.006) and mEASIX_alb (HR 1.38, 95% CI 1.09–1.73; p = 0.007) independently predicted OS after adjustment for baseline covariates (ISS stage, pre-transplant response, and age). EASIX remained independently prognostic in a day-100 landmark analysis (HR 1.35; p = 0.023). Critically, the PNI, prognostic for OS in univariate analysis (HR 0.973; p = 0.038), did not provide independent incremental prognostic value beyond the clinical model when EASIX was added (HR 0.99; p = 0.526); this does not establish shared information between EASIX and PNI. Conclusions: Pre-transplant EASIX and mEASIX_alb are independent prognostic biomarkers in MM-ASCT. The PNI did not provide independent incremental prognostic value beyond the clinical model. These scores may inform pre-transplant risk stratification, although the illustrative cutoffs require external validation before clinical use. EASIX retained prognostic significance across transplant eras and in a cytogenetically characterized subset, supporting its era-independent and cytogenetics-independent utility. Full article

Fms-related receptor tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations occur in approximately 20–25% of patients with acute myeloid leukemia (AML) and are associated with increased relapse risk and inferior survival outcomes. Although measurable residual disease (MRD) has become a key prognostic tool for guiding post-remission treatment decisions, FLT3-ITD was historically considered a suboptimal MRD marker because of its subclonal nature, structural heterogeneity and dynamic behavior during disease evolution. In addition, FLT3-ITD has not yet been fully integrated into routine MRD monitoring due to methodological limitations and a lack of standardized workflows. The latest European LeukemiaNet (ELN)-DAVID 2025 recommendations stressed the use of ultra-high sensitivity (UHS) next-generation sequencing (NGS) technologies to detect FLT3-ITD MRD with improved precision, enabling reliable longitudinal tracking of patient-specific clones at very low variant allele frequencies (VAF). Indeed, despite prospective evidence supporting this approach remaining limited, FLT3-ITD-based MRD monitoring is emerging as a clinically relevant prognostic indicator, contributing to the identification of patients at increased risk of relapse and refining risk stratification, while also informing therapeutic decision-making, particularly in the peri-transplant setting. The present review summarizes the biological underpinnings of FLT3-ITD mutated (FLT3-ITD^mut) AML, discusses the methodological challenges of MRD detection, and critically evaluates the evolving role of MRD in refining relapse prediction, supporting post-remission therapy tailoring, and contributing to a harmonized framework for FLT3-ITD^mut AML management. Full article