Search Results (17,964)

Heat stress is a growing concern in cattle production systems due to the increasing frequency and intensity of extreme weather events driven by climate change. This review synthesizes current knowledge on the multifaceted impacts of heat stress and focuses on nutritional strategies to mitigate its effects on ruminating cattle. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Heat stress adversely affects cattle physiology, behavior, rumen function, and overall productivity, particularly in dairy animals with high metabolic activity. During heat stress episodes, changes in the microbial population have been reported; however, there is no clear consensus, as findings vary widely among studies depending on diet, feed intake, animal type and experimental design. This variability limits the ability to draw general conclusions regarding changes in the rumen microbiome driven by heat stress. In this context, dietary nutritional intervention strategies offer a practical and scalable approach to enhance thermotolerance and maintain performance under heat stress conditions. Key nutritional strategies include modifications in diet composition to reduce metabolic heat production, with some approaches carrying potential risks to animal health, e.g., increasing dietary energy density through concentrates while minimizing forage content. Supplementation with rumen-protected nutrients like amino acids, vitamins, and minerals can be used to support immune function, antioxidant capacity, and metabolic stability. Polyphenols and betaine contribute to oxidative stress reduction and gut integrity, while probiotics may be used to improve rumen fermentation and nutrient utilization. Sensor technologies, including rumen boluses and wearable devices, offer the potential to monitor physiological responses to heat stress in real time and offer opportunities for precision feeding and early intervention. Most published studies only cover short periods of heat stress, and there is a lack of in vitro models simulating rumen hyperthermia. In parallel, future research should therefore prioritize longitudinal, in vivo trials that integrate physiological, metabolic, and microbial responses to understand the long term and systemic effect of heat stress. In addition, controlled trials in commercial settings are necessary to prove the transferability of results to commercial herds. A multidisciplinary approach combining nutritional, environmental, and technological strategies is likely to play an important role in safeguarding cattle welfare and productivity in a warming climate. Full article

Drought is among the most serious abiotic stresses affecting tomato production worldwide, especially under climate change. Plants exposed to repeated drought events may develop stress memory, allowing them to respond more efficiently to subsequent stress exposure. In this study, physiological and transcriptomic tools were combined to investigate dehydration stress memory in tomato (Solanum lycopersicum L.). Tomato plants were subjected to two consecutive drought stresses separated by a recovery stage, where control (C), first stress (S1), rehydration (H), and second stress (S2) stages were analyzed. Physiological measurements showed progressive reductions in relative water content (RWC) and PSII activity under drought stress, while proline accumulation was significantly increased during the second stress stage, indicating memory-associated adaptive responses. RNA sequencing revealed dramatic transcriptome reprogramming with thousands of differentially expressed genes (DEGs) across stress stages. Hierarchical clustering identified 30 distinct expression patterns among revealed DEGs, including clusters associated with transcriptional memory, adaptive responses, metabolic adjustment, and recovery processes. Several memory-associated clusters were enriched with transcription factors, signaling proteins, osmolyte-related genes, and reactive oxygen species detoxification enzymes. Gene Ontology analysis highlighted significant enrichment of pathways related to photosynthesis, response to water deprivation, ABA signaling, oxidative stress, carbohydrate metabolism, and chromatin organization. Recovery-associated expression of histone and chromatin remodeling genes indicates a potential involvement of epigenetic-related regulatory processes in dehydration stress memory in tomato. Tomato plants respond to repeated dehydration stress through coordinated physiological, metabolic, transcriptional, and epigenetic adjustments that improve stress adaptation. The identified candidate memory genes may provide useful targets for future breeding programs aimed at enhancing drought tolerance in tomato. Full article

Long-term maize storage causes oxidative deterioration, but its effects on intestinal redox status, systemic inflammation, and liver-related responses in ruminants remain unclear. Laminaria japonica polysaccharide (LJP) has antioxidant, immunomodulatory, and microbiota-regulating properties, but its efficacy during aged-maize feeding is unknown. This study evaluated whether LJP mitigates oxidative and inflammatory responses in Hu sheep fed aged maize and characterized cecal microbiome and metabolome alterations. Twenty-one Hu sheep (39.05 ± 3.55 kg) were assigned to three diets (n = 7) and fed for 10 weeks (a 14-day adaptation period followed by 8 weeks of treatment): normal maize (CK), aged maize (AM), or aged maize with 0.5% LJP (AML). Compared with CK, AM increased plasma lipopolysaccharide (0.428 vs. 0.379 EU/mL), TNF-α, and IL-1β, and raised ileal reactive oxygen species (248.79 vs. 166.23 fluorescence intensity/mg; p < 0.001) and malondialdehyde (1.87 vs. 1.63 nmol/L; p = 0.006), consistent with systemic inflammation and intestinal oxidative stress. AML lowered these inflammatory and oxidative indices and increased hepatic T-AOC (p = 0.009) and catalase activity (p = 0.013). Integrated 16S rRNA and untargeted metabolomic analysis revealed treatment-associated cecal microbe–metabolite associations. These findings indicate that aged-maize feeding was associated with intestinal and systemic redox–inflammatory changes in Hu sheep, whereas dietary LJP was associated with partial mitigation, potentially involving microbial and metabolic remodeling. Full article

Micro- and nanoplastics (MNPs) are now pervasive in human tissues, yet their biological behavior remains unexplained within conventional pharmacokinetic frameworks. Here, we propose that MNP distribution may follow a bioenergetic logic governed by cellular turnover and metabolic demand, rather than passive diffusion alone. Integrating the human autopsy literature datasets with programmatic biological parameters suggests that MNPs persist intracellularly and are propagated through cycles of cell death and renewal, establishing a previously unrecognized system of retention-driven recirculation. By integrating tissue-specific metabolic rates, macrophage abundance, and intracellular vulnerability indices across 19 organs, we define a hierarchy of susceptibility, with highest accumulation in the spleen, intestinal epithelium, lung, and bone marrow. This hierarchy maps onto clinical patterns of tissue dysfunction and supports a unifying mechanism in which oxidative stress, energetic instability, and chronic inflammation emerge as convergent responses to MNP burden. We further identify a minimal circulating signature—lactate, high-sensitivity C-reactive protein (hsCRP), and lactate dehydrogenase (LDH)—that reflects systemic bioenergetic disruption associated with MNP exposure. Together, this framework offers a conceptual shift from diffusion-limited to turnover-driven accumulation models, providing testable hypotheses for future prospective validation. Full article

Postbiotics are defined as preparations of inanimate microorganisms and/or their components that confer a health benefit on the host. Although interest in postbiotics has increased substantially, their translational use in functional foods remains insufficiently characterized with respect to preparation identity, production methodology, food-matrix compatibility, mechanistic specificity, and regulatory positioning. This PRISMA-guided structured review aims to synthesize current evidence on postbiotics in functional food and nutraceutical contexts, with particular emphasis on preparation-based characterization, gut–brain axis-related mechanisms and clinical findings, food matrix applicability, and regulatory and health-claim considerations. Unlike broader postbiotic reviews that mainly address definitions, general health effects, or technological stability, this review integrates preparation identity, production process, gut–brain axis-related evidence, food matrix compatibility, and regulatory/health-claim translation within a single functional food framework. A structured literature search was conducted in Scopus and Web of Science Core Collection and was completed on 16 February 2026. The search strategy included three conceptual blocks: postbiotic and inactivation-based preparation terms, functional food/nutraceutical and food matrix terms, and gut–brain axis-related clinical and mechanistic terms. Cosmetic, topical, veterinary, animal feed, and aquaculture-focused publications were excluded. The export files contained 131 records from Scopus and 136 from the Web of Science Core Collection, yielding 267 records after applying document-type and language filters. After manually removing duplicates, 237 unique records were screened. Following title/abstract screening, 176 records were excluded as outside the scope of the review, and 61 publications were retained for full-text assessment and final thematic synthesis. The review was reported according to applicable PRISMA 2020 items. The evidence was organized into three thematic domains: gut–brain axis-related clinical findings, mechanistic evidence, and food matrix/product development applications. Heat-inactivated preparations, including Lactobacillus gasseri CP2305 and Lactiplantibacillus plantarum SNK12, have shown preliminary effects on stress-related symptoms, sleep quality, and selected neuroendocrine or inflammatory biomarkers in human studies. Mechanistic pathways include gut barrier integrity, immunomodulation, short-chain fatty acid signaling, tryptophan–kynurenine–serotonin metabolism, vagal communication, and regulation of the hypothalamic–pituitary–adrenal axis. Food matrix studies support the potential application of postbiotics in fermented dairy products, cereal-based systems, plant-based matrices, powders, concentrates, and bioactive packaging; however, matrix-dependent effects on bioavailability, sensory quality, and biological activity remain incompletely defined. Postbiotics provide a stable translational platform for functional-food development, but their scientific and commercial use requires clear characterization of the microbial source, production process, inactivation method, retained active fractions, dose metric, delivery matrix, and clinically meaningful endpoint. Future studies should avoid broad category-level claims and prioritize preparation- and matrix-defined human evidence with standardized safety reporting. Full article

Physical infrastructure failure induces topological phase transitions in financial networks that existing systemic risk models cannot detect, attribute, or govern. This study introduces CASCADEnt (Cascading Systemic-Entropy-Detecting Network), a physics-informed entropy protocol for infrastructure-coupled financial hypergraphs. The model integrates three components: (i) a Landauer-motivated entropy threshold ($S^{*}=2.852$ nats) that detects imminent metabolic arrest before it manifests as market stress; (ii) Gradient-Boosted Integrated Gradients (GB-IG) metabolic centrality that attributes systemic collapse to the specific apex nodes driving it; and (iii) a Lyapunov-constrained Hamilton–Jacobi–Bellman protocol that governs macroprudential intervention with deterministic stability tendency under a linear control assumption (Theorem 1); stochastic extensions remain future work. The key variables are daily equity returns and hypergraph topology for 19 JSE Top40 securities, integrated with Eskom Energy Availability Factor (EAF) telemetry and CBOE VIX ($T=2838$ trading days, January 2015–April 2026). CASCADEnt achieves F1 = 0.643 at a 96 h early-warning lead time, outperforming all advance-warning baselines by 23.6 percentage points, with a false alarm rate of zero across 553 out-of-distribution days. Twelve apex nodes concentrate 85.5% of total system entropy, providing a governance target for macroprudential capital buffer design in infrastructure-dependent emerging economies. Full article

Diabetic retinopathy (DR) reflects retinal microvascular injury and systemic immune-metabolic stress, and most public DR transcriptomic datasets lack paired microbiome/metabolomic profiles. We used gutMGene v2.0 as a curated microbe/metabolite–host gene prior and integrated it with peripheral blood transcriptomics from GSE221521. Candidate genes were refined by weighted gene co-expression network analysis (WGCNA), repeated resampling, cross-dataset assessment, mechanism scoring, peripheral blood mononuclear cell (PBMC) single-cell localization and filamin A (FLNA)-centered single-cell gene regulatory network (GRN) virtual knockout. The gutMGene prior contained 238 host genes; 15 DR-associated genes overlapped this prior, and WGCNA retained ten candidate gut microbe and microbial metabolite-related genes (GMMRGs): FLNA, AKT1, IRAK1, BCL10, CDK6, CTSD, JUP, CXCL1, CXCR2 and IL4R. Resampling prioritized FLNA as the most consistent candidate. Cross-dataset assessment localized the strongest signal to type 2 diabetes (T2D) PBMCs, retinal endothelial cells and advanced proliferative diabetic retinopathy with diabetic macular edema (PDR + DME) retinal tissue, with weaker separation in whole blood, broad retinal tissue and six-donor type 1 diabetes (T1D) PBMCs. FLNA virtual knockout predicted cell-context-dependent perturbation of immune-related transcriptional programs, including IL4R in DR B cells and CTSD in DR monocytes/NK cells. This prior-guided study identifies FLNA within a ten-gene GMMRG set as a circulating host-response signal that links curated microbe/metabolite–host records to immune-vascular and cytoskeletal remodeling in DR. Full article

Background: Urinary incontinence (UI) is a common condition that affects women’s physical, psychological, and social well-being. Evidence from Central Asia remains limited. This study assessed factors associated with UI, its subtypes, and quality-of-life impairment among women in Kazakhstan. Methods: A multicenter age-matched case–control study was conducted from February to May 2025 in healthcare facilities across Kazakhstan. The study included 2061 women. Sociodemographic, obstetric, lifestyle, comorbidity, and symptom data were collected using a structured questionnaire. Quality of life was assessed using Kazakh and Russian versions of the Incontinence Quality of Life Questionnaire (I-QOL). Multivariable logistic regression with backward elimination identified factors independently associated with UI. Results: UI was identified in 687 women (33.3%). Stress urinary incontinence (SUI) was the most common subtype (n = 356; 51.8%), followed by urgency urinary incontinence (UUI) (n = 191; 27.8%) and mixed urinary incontinence (MUI) (n = 140; 20.4%). UI was independently associated with vaginal delivery (OR = 1.48), multiple birth (OR = 2.26), macrosomia (OR = 1.83), and BMI ≥ 25 kg/m² (OR = 2.08). UUI showed the greatest burden, including the lowest total I-QOL score [36.4 (23.9–88.6)]. Conclusions: UI in Kazakhstan was mainly associated with obstetric and metabolic factors, supporting targeted prevention through weight management, antenatal care, and early pelvic floor assessment. Full article

Age-associated metabolic dysfunction is commonly defined by abnormalities in adiposity, glucose regulation, lipid metabolism, and blood pressure. Although clinically useful, these criteria do not fully capture the biological heterogeneity that explains why older adults with similar metabolic profiles may follow divergent trajectories toward type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, frailty or multimorbidity. This narrative Review summarizes clinical, translational, and mechanistic evidence on the biological processes that shape metabolic aging, with particular emphasis on inflammaging, immunosenescence, cellular senescence, oxidative stress, mitochondrial dysfunction, adipose tissue dysfunction, endothelial injury, and inflammation-related microRNAs. We first discuss how chronic low-grade inflammation and immune remodeling alter the interpretation of conventional metabolic syndrome components in older adults. We then review redox imbalance and mitochondrial stress as amplifiers of insulin resistance, lipid injury, vascular dysfunction, and tissue remodeling. The review also examines inflammation-related microRNAs, including circulating and extracellular-vesicle-associated miRNAs, as post-transcriptional regulators that may connect inflammatory, metabolic, and redox pathways. Finally, we discuss how conventional metabolic markers may be integrated with inflammatory mediators, oxidative-stress indicators, adipokines, endothelial and senescence-related markers, and miRNA profiles to improve biological interpretation of metabolic risk. Within this context, we present the Inflammaging–Redox–InflammamiR Axis as a conceptual framework for organizing these overlapping mechanisms rather than as an established diagnostic or causal model. The proposed biomarker tiers and candidate risk phenotypes are author-derived, hypothesis-generating constructs intended to guide future longitudinal and interventional research. Clinical translation will require standardized assays, longitudinal validation, external replication, and intervention studies. Full article

Nitric oxide (NO) is a small, highly reactive gaseous signaling molecule that plays diverse and context-dependent roles in microbial physiology and host–microbe interactions. Over the past decade, increasing evidence has revealed the dual nature of NO as both an antimicrobial effector and a signaling mediator involved in microbial stress responses, metabolism, biofilm dynamics, quorum sensing, virulence regulation, and symbiotic interactions. In microbial systems, NO influences adaptation to environmental stress and contributes to mechanisms associated with persistence and antimicrobial resistance. In host organisms, NO functions as a key component of innate immunity while also participating in beneficial interactions involving rhizobia, mycorrhizal fungi, and probiotic microorganisms. Despite its biological significance, accurate detection and quantification of NO remain challenging because of its transient nature, high reactivity, low physiological concentrations, and interference from related reactive oxygen and nitrogen species. Recent advances in biosensing technologies have substantially improved NO detection capabilities through the development of electrochemical, optical, enzyme-based, microfluidic, wearable, and implantable sensing platforms. These innovations are complemented by analytical techniques including electron paramagnetic resonance spectroscopy, mass spectrometry, fluorescence-based imaging, and advanced microscopy, which enhance sensitivity, specificity, and spatiotemporal resolution in complex biological environments. Concurrently, statistical and computational approaches—including sensor calibration models, multivariate analyses, machine learning algorithms, and bioinformatics pipelines—have become increasingly important for extracting biologically meaningful information from NO-related datasets. Unlike previous reviews that primarily focus on either NO biology or sensing technologies, this review integrates current knowledge of NO-mediated microbial physiology and host–microbe interactions with recent developments in biosensor engineering, analytical methodologies, statistical frameworks, and emerging artificial intelligence (AI)-driven data interpretation. We further highlight applications of NO detection in infectious disease diagnostics, antimicrobial screening, probiotic and biofertilizer evaluation, environmental microbiome monitoring, and real-time studies of symbiosis and infection. Finally, future directions including miniaturized sensing platforms, multi-omics integration, AI-assisted analytics, and sensor standardization are discussed. By unifying molecular, analytical, and computational perspectives, this review provides a multidisciplinary framework and roadmap for advancing NO-based research and translational applications across microbial, environmental, and host-associated systems. Full article

Oyster-associated microbiomes represent a dynamic interface between marine hosts and their environment, yet the diversity, evolution, and functional potential of their associated cyanobacteria remain poorly understood. For microbial organisms, such as cyanobacteria, survival requires adaptation to several environmental pressures, including higher metal concentrations and osmotic stress. To investigate these adaptations, two cyanobacterial strains, CENA647 and CENA648, were isolated from oyster surfaces sampled along the Amazon coast. Genomic analysis and untargeted metabolomics were conducted to investigate the taxonomy and functional potential of these strains. Both genomes exhibited high completeness (>99.2%) and low contamination (<2.2%). The total lengths differed, with 8.3 Mbp for CENA647 and 6.5 Mbp for CENA648. The genome size correlated with the number of identified coding regions: 7593 for CENA647 and 5541 for CENA648. Phylogenetic analysis highlights their taxonomic relationships within cyanobacteria adapted to fluctuating salinity, including the first description of the genus Thainema in South America. Comparative genome mining revealed extensive genetic repertoires associated with osmoregulation and metal resistance, consistent with adaptation to oyster-associated environments. Both strains shared predicted metabolites annotated in the metabolomes, with a wide range of compound classes, including amino acids, terpenes, fatty acids, and peptides, as well as several unannotated molecular features. Overall, our findings expand current knowledge of oyster-associated cyanobacteria and highlight their metabolic diversity in the Amazon region, as well as genomic traits that may be associated with adaptation to dynamic estuarine environments. Full article

Oxidative stress contributes to retinal neurovascular injury through inflammation, mitochondrial dysfunction, blood–retinal barrier (BRB) disruption, microcirculatory impairment, and regulated cell death. Hydroxysafflor yellow A (HSYA), a water-soluble quinochalcone C-glycoside derived from safflower (Carthamus tinctorius L.), modulates oxidative and inflammatory signaling, apoptosis, mitochondrial injury, endothelial barrier dysfunction, and neurovascular damage in experimental ischemic, inflammatory, and metabolic disorders. This review critically evaluates the direct ocular evidence for HSYA in diabetic retinopathy and examines the systemic-to-ocular pharmacokinetic and delivery barriers that constrain its ophthalmic translation. Current ocular evidence is limited and concentrated mainly in DR models, in which HSYA attenuates oxidative stress, inflammation, BRB disruption, and apoptosis, potentially through Nrf2/HO-1 signaling. Evidence in retinal photic injury is limited, whereas the proposed relevance of HSYA to retinal ischemia–reperfusion injury, glaucoma, and AMD remains largely hypothesis-generating. The principal translational challenge is whether HSYA can achieve pharmacologically relevant exposure in ocular target tissues. Future studies should integrate dose, plasma and ocular exposure, target engagement, retinal structure, local safety, and visual function in disease-specific models. Accordingly, evidence from non-DR models is discussed primarily to define mechanistic hypotheses and experimental priorities rather than to establish ophthalmic efficacy. Full article

Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic targets, but rather as the clinical expression of persistent molecular activity involving multiple interconnected organs and pathways. Insulin resistance, metaflammation, oxidative stress, mitochondrial dysfunction, lipotoxicity, endothelial impairment, hepatic metabolic dysregulation, renal inflammation, fibrotic remodeling, and metabolic memory interact within a dynamic network linking adipose tissue, liver, kidney, immune cells, and vasculature. In this review, we discuss the biochemical and molecular drivers of cardiometabolic residual risk in T2D, with particular emphasis on impaired insulin receptor substrate/PI3K/Akt signaling, stress-kinase activation, NLRP3 inflammasome priming and assembly, MASLD-related lipotoxicity and fibrogenesis, podocyte and tubular injury, endothelial nitric oxide synthase uncoupling, AGE-RAGE signaling, and thrombo-inflammatory vascular injury. These pathways explain why biological vulnerability may persist even when conventional clinical parameters appear adequately controlled. We also examine the role of translational biomarkers and simple clinical indices, including TyG-derived indices, adiposity markers, hepatic steatosis and fibrosis scores, albuminuria, eGFR, and lipid-related markers, as accessible windows into active biological pathways. Finally, we review how contemporary therapeutic strategies may modulate selected components of this residual-risk network. A pathway-centered interpretation of T2D may support more precise residual-risk phenotyping and help move cardiometabolic care beyond isolated target control toward mechanism-based prevention. This review further links these mechanisms to the contemporary cardiovascular–kidney–metabolic (CKM) framework, as defined by the 2026 AHA/ACC/ADA/ASN CKM Guideline, and disaggregates the underlying molecular network into organ-specific pathway cascades that make the causal relationships between metabolic, inflammatory, hepatic, renal, and vascular injury more explicit. Full article

Background/Objectives: This study is the first to investigate the potential mechanism of star anise extract (SAE) in protecting against cold stress-aggravated acute lung injury (CSALI) in rats. Methods: A rat CSALI model was induced via combined lipopolysaccharide challenge and cold stress exposure. The preventive effects of SAE were evaluated using cytotoxicity assays, quantification of biochemical indices and inflammatory factors, and histopathological examination. Ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC–HRMS)-based serum metabolomics was employed to systematically profile CSALI-associated metabolic alterations and decipher the potential mechanism underlying the preventive effects of SAE. Results: SAE alleviated pathological progression of CSALI, suppressed inflammatory cell migration, markedly reduced pulmonary inflammatory cell infiltration, and ameliorated lung tissue injury in CSALI rats. SAE also improved abnormal liver function indicators and lowered the levels of pro-inflammatory factors in both serum and bronchoalveolar lavage fluid (BALF). Serum metabolomics analysis identified and annotated 24 disease-altered differential metabolites and evaluated the protective effects of SAE on them. These metabolites were significantly enriched in two key metabolic pathways related to the pathogenesis of CSALI, including arachidonic acid metabolism and glycerophospholipid metabolism. Furthermore, based on metabolite changes, phospholipase A2 was hypothesized as a potential key regulatory factor that may cooperate with arachidonic metabolism to suppress the inflammatory cascade. Conclusions: These findings demonstrated that SAE exerted prominent anti-inflammatory activity and effectively protected against lung injury in CSALI rats. Full article

Phytobiotics are promising dietary tools to improve metabolic stability and physiological resilience against chemical stressors in aquaculture. This study evaluated nrf2-linked antioxidant and metabolic modulation by dietary Origanum vulgare essential oil (OEO) in Nile tilapia (Oreochromis niloticus) under malathion-induced organophosphate stress. Fish, with an initial weight of 5.76 ± 0.56 g, were distributed in three tanks per treatment, with 15 fish per tank, and fed diets containing 0 (control), 0.75, 1.50, 2.25 and 3.00 g kg⁻¹ OEO for eight weeks, followed by exposure to malathion (7.04 mg L⁻¹) for 96 h. OEO enhanced (p < 0.05) growth performance, feed utilisation, and survival after exposure, with the greatest productive and survival outcomes at 3.00 g kg⁻¹. Fish that received the supplement also had lower (p < 0.05) lipid peroxidation, better antioxidant enzyme activity and a more favourable modulation of nrf2, gpx and keap1 expression, together with biochemical and histological patterns that were consistent with a better condition of the liver and kidney. The heatmap and PCA supported a treatment-related separation, with 2.25 and 3.00 g kg⁻¹ OEO showing the most favourable integrated physiological profiles. Dietary OEO was associated with antioxidant, metabolic and tissue-level resilience linked to modulation of nrf2-related transcriptional responses. Full article