Abstract: The dominant narrative of autonomic nervous function remains essentially that proposed by Walter B. Cannon over a hundred years ago. It emphasizes sympathetic mediation of “fight-or-flight” responses and catabolism and associates the parasympathetic system with “rest-and-digest” functions and anabolism. Dual innervation of tissues and an antagonistic relationship between the divisions is presented as the rule, with minor exceptions. Extensive evidence accumulated over the past century renders these generalizations untenable, as autonomic neuroscientists have been pointing out for decades. Yet such critiques have not changed how the system is taught or understood. To remedy this situation, it is proposed that an alternative framework is needed that aptly summarizes sympathetic and parasympathetic functions, respectively. Here, following a systematic critique of the traditional approach, such an alternative is proposed based on a consideration, first, of functions in tissues innervated by only one branch, such as the kidneys, and then, of specific functions in tissues receiving dual innervation where distinct regulatory responsibilities of one or the other branch is clear, e.g. respiratory sinus arrhythmia and the pupillary light reflex. The proposed schema describes the sympathetic division as the body’s “quartermaster,” responsible for regulating physico-chemical conditions and distributing metabolic resources to meet, and where necessary adjust, current and anticipated demand, under all circumstances. In contrast, the parasympathetic division is described as the body’s “coordinator,” regulating secretory and smooth muscle activity involved in interactions and exchanges with the outside world—eating, breathing, speaking, voiding, looking, mating, moving, etc—often closely articulated with associated somatic motor activity. The schema emphasizes that in each tissue, the activity of the respective branches relates to their respective regulatory responsibilities, and not to a generically counterbalancing relationship to the other. The proposed alternative leads to novel hypotheses regarding the function of autonomic innervation in cases where its physiological importance remains obscure, such as the parasympathetic supplies to pulmonary and cerebral vasculature and to airway smooth muscle. It is offered to stimulate debate directed toward the creation of a consensus alternative narrative that can displace the misleading traditional narrative and advance a more realistic view of autonomic function.

Abstract: This paper presents the Proximal Chemical Mandate Principle, a theoretical framework proposing that behavior in organisms with neurochemical systems is governed by two invariant mandates: reward signal maximization (R↑) and stress signal minimization (S↓). We develop a three-tiered hierarchy where proximal chemical drivers (Px) implement evolved functional objectives (Xm) through object selection criteria (OsC) detected by identifier sensors (I-s), producing ultimate outcomes (Uo) that are environmentally contingent. The framework identifies three environmental domains—Natural Selection Field, Natural Epistemophilia Field, and Natural Counterproductive Field—where identical neurochemical optimization processes yield adaptive, mixed, or maladaptive outcomes respectively. We integrate evidence from neuroscience and propose conceptual thought experiments to test necessary and sufficient conditions of the mandates. The model suggests consciousness functions as a state reflection of ongoing neurochemical computations rather than as a causal agent, with philosophical implications for understanding agency and decision-making. The framework provides a unified account of behaviors ranging from basic survival to complex cognitive processes through deterministic neurochemical optimization principles.

Abstract: The effects of forced aeration on sweet potato growth and yield by decreasing CO2 concentrations in the rooting zone were investigated.. The following four experiments were conducted with forced aeration in the rooting zone: (1) with air containing different CO2 concentrations to clarify the effects of CO2 in the rooting zone on the net photosynthetic rate and leaf conductance, (2) with atmospheric air into cultivating soil ridges through porous pipes as a feasibility study, (3) with varying forced-aeration rates, and (4) with varying time intervals of forced aeration to find a more efficient aeration method. The results are summarized as follows: (1) During the six-week growing period, the mean values of net photosynthetic rates and leaf conductance for 1% CO2 and 2% CO2 were 0.8 and 0.7 times, respectively, those in the Control with 0.04% CO2. (2) When the aeration rate was 1.5 L min-1 per 1 m of ridge length, the CO2 concentration reduced to 0.1-0.2% in the rooting zone, whereas the control ridge with non-forced aeration was 0.5-1.4% CO2. The fresh and dry weight yields of sweet potato tubers were 1.18 and 1.19 times those of the control, respectively. (3) The CO2 concentrations decreased as the aeration rate increased. The dry weights of tuberous roots in forced-aeration ridges at aeration rates of 1.25 and 2.5 L min-1 were 1.19 and 1.26 times those in the control, respectively. Sweet potato growth was promoted when forced aeration reduced CO2 in the rooting zone. (4) The yield increased by 24% even when forced aeration was performed for just 15 min per day after irrigation. In conclusion, forced aeration into the rooting zone decreased CO2 concentrations and increased sweet potato yield by approximately 20%. The sweet potato yield can be increased even with forced aeration for 15 min per day. Forced aeration to reduce CO2 concentrations in the rooting zone can improve the yield of root crops.

Abstract: We present a formal synthesis of the TCGS-SEQUENTION framework with foundational research in collective animal behavior. We posit that the "superorganism" concept, as defined by Wheeler , is not an analogy but a precise description of a coherent three-dimensional (3-D) shadow manifold \( (\Sigma_{bio}) \)—a projection of a single four-dimensional (4-D) source singularity (Axiom A2: Identity-of-Source). This projection-first ontology geometrically resolves the "combination problem" of panpsychism [1]; the colony mind does not "emerge" from the combination of 3-D ant-minds but is a \emph{projection} of a unitary 4-D content. We map Wheeler's "germ-plasm" (queen) and "soma" (worker) duality to the empirically observed "generalized" (queen) and "specialized" (worker) brain architectures , demonstrating they are differential projections of this single source. We argue that 3-D collective behaviors—such as the "distributed process" of task allocation and "multiscale competency" —are the observable phenomenology of the shadow collective following the gradients of the 4-D biological informational potential (\emph{U}), as defined by the SEQUENTION constitutive law \( J = \mu_{bio}(...) \nabla\mathcal{U} \). Finally, we demonstrate that empirical 3-D non-local phenomena, specifically the "scale-free correlations" \( (\xi \sim L) \) observed in flocks , are the definitive "smoking gun" signature of the framework's "Retrocausal, Non-Local Counterspace Coupling" (\( K_s \)) kernel , which provides non-local coordination across foliation leaves.

Abstract:

Soybean (Glycine max) is a globally important crop, but its productivity is often limited by suboptimal nodulation and nitrogen fixation, particularly under stress conditions. Bradyrhizobium diazoefficiens strain USDA110 is widely applied to enhance nodulation, yet its efficiency can be further improved by phytohormone modulation. This study examined the effects of seed coatings containing plant growth regulators (PGRs)—acetylsalicylic acid (ASA), aminoethoxyvinylglycine (AVG), indole-3-butyric acid (IBA), and 6-benzylaminopurine (BAP)—at varying concentrations from 5 – 500 nM, in combination with USDA110, on nodulation, nitrogenase activity, ethylene emission, physiological traits, and yield of soybean cultivar CM60. Laboratory assays identified 50 nM AVG, 5 nM IBA, and 5 nM ASA as optimal treatments, significantly enhancing nodule number and nitrogenase activity. Greenhouse trials under both well-watered and water-deficit conditions further demonstrated that USDA110 combined with AVG or IBA markedly improved photosynthesis, stomatal conductance, transpiration, plant height, and yield components compared with USDA110 or PGRs applied alone. Notably, USDA110 + AVG/IBA treatments sustained higher seed weight under drought, indicating strong synergistic effects in mitigating stress impacts. These findings highlighted that integrating USDA110 with specific PGRs represented a promising strategy to optimize nitrogen fixation and enhanced soybean productivity under both favorable and challenging conditions.

Abstract: Chronic stress alters hypothalamic-pituitary-adrenal (HPA) axis function, influencing corticosterone regulation and adaptive responses. Identifying distinct response patterns can provide insight into individual variability in stress adaptation. This study is aimed to assess variability in HPA axis sensitivity following chronic social defeat stress. Male C57BL6 mice were exposed to chronic social defeat stress (CSDS) for 30 days. In order to evaluate integrity of negative feedback loop of HPA axis dexamethasone suppression test (DST) was used. Corticosterone levels were measured following saline or low-dose dexamethasone administration at 10 and 30 days. K-means clustering by corticosterone levels after saline and dexamethasone administration was applied to identify distinct response profiles. Behavioral testing (open field, elevated plus maze, social interaction test, partition, social defeat, forced swimming test, sucrose preference test) and qPCR analysis of HPA axis-related genes in hypothalamus (Crh, Crhr1, Crhbp, Fkbp5, Nr3c1), pituitary gland (Pomc, Crhr1, Nr3c1, Nr3c2), and corticosterone synthesis genes in adrenal glands (Cyp11a1, Cyp11b1, Hsd11b1, Mc2r, Star, Fkbp5, Nr3c1) was performed. Cluster analysis identified 3 distinct response profiles differing in baseline and dexamethasone-suppressed corticosterone levels. Clusters also exhibited differences in behavioral phenotypes and HPA axis gene expression. Cluster 1 showed low basal corticosterone and an abnormal dexamethasone suppression response, without significant Crh or Crhbp dysregulation in the hypothalamus. Cluster 2 exhibited elevated basal corticosterone, a blunted dexamethasone response, anhedonia, and reduced immobility in the forced swim test; increased Crh and reduced Fkbp5 suggest enhanced glucocorticoid receptor sensitivity and sustained hypercortisolemia. Cluster 3, characterized by normal basal corticosterone and normal dexamethasone response, showed upregulation of Crh and Crhbp, consistent with balanced and potentially adaptive HPA axis regulation under chronic stress. Corticosterone response heterogeneity reflects distinct adaptive trajectories under chronic stress. Identifying behavioral markers of these strategies may improve understanding of stress vulnerability and resilience mechanisms, with implications for stress-related disorders.

Abstract: Data from the ERA-CVD Consortium PREMED-CAD-Precision Medicine in Coronary Artery Disease were used for identification of molecular signature for prediction of Ishemia. Regression study found association of Ischemia to Diabetes Mellitus Type 2 (p.value<=0.05). Logistic regression was applied to each layer of data (microRNA, metabolites and biomarkers), then backward-forward stepwise selection was applied to select one molecular signature with 23 variables was proposed.

Abstract: Classical branching-process theory, developed by Galton and Watson in the nineteenth century and later refined by Fisher and Haldane, provides the formal framework for quantifying the fate of new mutants, new viral and bacterial pathogens, new coloniza-tion of invasive species, etc. It is a powerful tool to quantify and predict the effect of differential reproductive success on the speciation potential of evolutionary lineages. Here, I revisit the conceptual framework of the branching process, detail its mathe-matical development over time, tie up a few historical loose strings, and highlight its potential applications in modern ecology and evolutionary biology.

Abstract:

The genus Allium L. (Amaryllidaceae) comprises ecologically flexible species widespread across mountain ecosystems, yet the relationships among morphology, environment, and genetics within section Schoenoprasum in Central Asia remain poorly understood. This study investigated four taxa – A. ledebourianum, A. ivasczenkoae, A. ubinicum, and A. schoenoprasum – from the Kazakhstan Altai to assess their morphological variation, ecological preferences, phytochemical activity, and genetic relationships. Populations occurred on gentle chernozem slopes under humid, nutrient-rich conditions and showed stable regeneration dominated by young individuals. Morphometric analyses revealed pronounced interspecific differentiation: A. ledebourianum attained the greatest height and umbel size, whereas A. ubinicum was smallest but possessed proportionally larger floral organs. Principal component analysis explained 94% of total variance, distinguishing A. ubinicum and A. schoenoprasum from the remaining taxa. Floral traits correlated significantly with temperature, moisture, and soil reaction, indicating strong environmental influence on phenotype. Extract assays showed variable bioactivity, with A. ubinicum displaying the highest antioxidant potential (IC₅₀ = 88 µL) and highest cytotoxicity (LC₅₀ of 5.9 μg/mL), while A. ledebourianum shows no antioxidant activity and the lowest toxicity (LC₅₀ of 10.9 μg/mL). Phylogenetic reconstruction using matK, rbcL, and psbA–trnH chloroplast markers confirmed close affinity between A. ledebourianum and A. ivasczenkoae, while A. ubinicum formed a distinct lineage. Together, morphological, ecological, and molecular data highlight the Kazakhstan Altai as a center of diversification for section Schoenoprasum. These results emphasize the adaptive plasticity of endemic Allium species and their potential as sources of valuable bioactive compounds, underscoring the importance of conserving genetically and morphologically diverse populations in mountain ecosystems.

Abstract: Background. NOTCH receptors play a pivotal role in carcinogenesis. Upon ligand binding, a cascade of proteolytic cleavages mediated by ADAM proteases and the γ-secretase complex activates the receptor, culminating in the release of the NOTCH intracellular domain (NICD). NICD translocates to the nucleus, where it modulates gene expression. The main objective of this review is to analyze γ-secretase inhibitors (GSIs) as promising anticancer agents in preclinical studies and clinical trials, focusing on their ability to disrupt tumor progression, cancer stem cell maintenance, and resistance to conventional therapies.Methods. A systematic search was conducted in the ISI Web of Science, PubMed, and Scopus databases, following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Inclusion criteria required articles to be preclinical studies conducted in vitro or in vivo using mice or other animal models, or clinical trials in humans investigating GSIs either as monotherapy or in combination with other antitumor drugs targeting TNBC, metastatic melanoma, PDAC, GC, and NSCLC. Exclusion criteria included duplicate publications, articles not originally written in English, and studies focusing on GSIs in non-cancer pathologies such as Alzheimer’s disease. Studies investigating alternative therapeutic targets within the NOTCH signaling pathway that did not directly involve GSIs were also excluded. Risk of bias was assessed by evaluating study methodology, including randomization, blinding, handling of missing data, and other factors that could affect validity. Research synthesis was qualitative, summarizing and comparing the findings of the included studies.Results. We evaluated the main therapeutic advances achieved through GSIs in vitro, in vivo, and in clinical trials across cancers where NOTCH signaling is oncogenic. The dataset included 10 articles on NSCLC, 17 on breast cancer and TNBC, 14 on metastatic melanoma, 13 on GC, 10 on PDAC, 20 on general aspects of NOTCH signaling and therapeutic strategies in cancer, and 2 web pages on global cancer epidemiology. Although GSIs have entered clinical trials for PDAC, metastatic melanoma, and TNBC, their efficacy remains limited. However, combinatorial strategies involving GSIs, ADAM secretase inhibitors, and other antitumor agents have shown promise in improving treatment outcomes and reducing side effects.Discussion. Despite encouraging preclinical findings across multiple cancer types, clinical trials have not yet yielded the expected results, with the exception of TNBC. Future research should aim to identify the specific NOTCH receptor(s) involved in each tumor type and tailor therapies, accordingly, considering gender-based prevalence differences. Additionally, nanoparticle-based delivery systems and synergistic drug combinations may enhance the therapeutic index of GSIs and ADAM inhibitors while minimizing adverse effects.

Abstract: Dengue is a growing mosquito-borne viral infection of global concern. It remains a major public health challenge in Nepal, where reliable biomarkers for disease staging and prognosis are lacking. In this study, we investigated circulating microRNA-1246 (miR-1246) as a potential diagnostic and prognostic marker in dengue infection. Serum samples from 21 dengue-positive patients and 20 healthy controls were analyzed by quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), with RNU6 as an internal control. Dengue patients showed markedly elevated miR-1246 levels, with a mean 47-fold increase compared to controls (p = 0.001). Expression varied by disease stage, peaking in IgM positive cases, declining in weakly positive IgM patients, and reaching the lowest levels in IgG positive convalescent cases, a pattern consistent with clinical parameters such as platelet recovery. Receiver Operating Characteristic (ROC) analysis further highlighted diagnostic potential, yielding an Area Under the Curve (AUC) of 0.79, sensitivity of 95.24%, and specificity of 60.00%. These findings imply that miR-1246 is drastically dysregulated during dengue infection and could be a useful biomarker for tracking the intensity and course of the illness.

Abstract: Quinoa (Chenopodium quinoa, 2n = 4x = 36, AABB subgenomes) is a highly nutritious crop with potential to diversify global diets and alleviate malnutrition. It is also adaptable for production in soils increasingly affected by salinization and water scarcity. Quinoa was domesticated and artificially selected as a crop within the Andes Mountains, the geographically isolated Mediterranean climate zone of coastal Chile, and along the northwestern fringe of the Argentine dry Pampas. In addition, there is now abundant information regarding the wild species that were its immediate ancestors and which should be viewed as its secondary and tertiary breeding gene pools. These same ancestors contributed to independent domestications of the other forms of “quinoa” in ancient Mesoamerica and eastern North America from a common AABB ancestor-species, C. berlandieri, known commonly as pitseed goosefoot (PG). This review explores the biogeography of the diploid and polyploid relatives of the AABB allotetraploid goosefoot complex (ATGC). The seven or more ecotypes of PG, including the South American taxon C. hircinum or avian goosefoot, contain broad genetic variability and some can be used directly as crossing partners in making quinoa breeding populations. Of the extant diploid relatives, C. subglabrum is most closely related to the original maternal subgenome A of PG, while C. suecicum or C. ficifolium are most closely related to paternal subgenome B. These and the other AA and BB diploids are valuable model organisms for locating and modifying genes of interest and their expression, the ultimate goals being to increase quinoa’s yield potential, improve its nutritional attributes, explore value-adding industrial uses, and enhance quinoa's already formidable mechanisms to resist environmental stresses.

Abstract:

Abstract: The advent of CRISPR-based genome editing has transformed the conceptual framework of oncology—from descriptive molecular profiling to functional genome engineering. By enabling precise, programmable, and multiplex control of cancer-associated genes, CRISPR/Cas systems are reshaping how we model tumorigenesis, predict drug response, and design patient-tailored interventions. This Perspective discusses how CRISPR technologies are redefining precision oncology, the biological and ethical challenges that impede their clinical translation, and emerging strategies that integrate gene editing with immunotherapy, synthetic biology, and systems medicine. We argue that the future of cancer therapy lies not merely in editing genes but in orchestrating the dynamic networks that sustain malignancy.

Abstract: Amazonian large trees act as central elements of forest ecosystems, storing a disproportionate fraction of aboveground biomass. However, these trees are not randomly distributed across the landscape, and it is expected that edaphic attributes influence floristic composition, forest structure, and vegetation biomass. In this study, we investigated how soil variation affects the diversity and biomass of large trees. Forest inventories were conducted at five sites within protected areas in the states of Pará and Amapá. Aboveground biomass was estimated using allometric equations, while soil samples were analyzed for their physical and chemical properties. Diversity indices, rarefaction, Redundancy Analysis, and Generalized Additive Models were applied. Edaphic variables such as soil pH, organic matter, phosphorus, and aluminum were associated with floristic composition and the biomass of these individuals. Trees with a diameter at breast height greater than or equal to 70 centimeters accounted for up to 80% of total biomass, revealing a pattern of biomass hyperdominance. The results indicate that the occurrence of large trees is related to edaphic and structural factors, suggesting that these individuals are not randomly distributed along soil gradients. Understanding these patterns is essential for improving ecological models, biomass extrapolations, and management strategies aimed at conserving the Amazon rainforest.

Abstract: Training adaptation encompasses not only muscular and metabolic remodeling but also personality‑linked traits such as motivation, self‑regulation, and resilience. This narrative review examines how training load oscillation (TLO)—the deliberate variation of exercise intensity, volume, and substrate availability—may function as a systemic epigenetic stimulus. Fluctuating energetic states reconfigure AMP‑activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), calcium/calmodulin‑dependent protein kinase II (CaMKII) and sirtuin‑1 (SIRT1) signaling, influencing DNA methylation, histone acetylation, and microRNA programs governed by peroxisome proliferator‑activated receptor‑γ coactivator‑1α (PGC‑1α) and brain‑derived neurotrophic factor (BDNF). We synthesize evidence linking these molecular adaptations to behavioral consistency and stress tolerance. Building on this literature, we propose a systems model of molecular–behavioral coupling in which TLO entrains phase‑shifted AMPK/SIRT1 and mTOR windows, with CaMKII pulses and a delayed BDNF crest; over time, this rhythm may promote conditions that enable epigenetic resonance, potentially aligning energetic signals with motivational processes. The framework suggests testable predictions (e.g., amplitude‑dependent PGC‑1α demethylation and BDNF promoter acetylation; NR3C1 recalibration with recovery‑weighted cycles) and practical implications for precision training that times nutritional and cognitive inputs to molecular windows. Understanding TLO as an entrainment signal may help integrate physiology and psychology within a coherent strategy for durable performance.

Abstract: Background: Seasonal influenza remains a significant public health problem, and the constant antigenic drift of viruses requires regular vaccine updates. mRNA vaccines offer a promising platform for the development of new, effective influenza vaccines. Administration of the naked mRNA vaccine using a needle-free jet injection system further enhances its safety, reduces cost, and eliminates the need for lipid nanoparticles, which are traditionally used for mRNA delivery. Lyophilization of naked mRNA allows for longterm storage at +4°C. Methods: We designed and produced an mRNA vaccine against seasonal influenza, designated mRNA-Vector-Flu, encoding the hemagglutinin (HA) of the A/Wisconsin/67/2022(H1N1)pdm09, A/Darwin/9/2021(H3N2), and B/Austria/1359417/2021 strains. The vaccine was lyophilized and stored for 1 month in a refrigerator (+4°C). A comparative immunogenicity study was conducted between synthesized immediately before use prepared and lyophilized naked mRNA-Vector-Flu. The preparations were administered to BALB/c mice using a jet needleless injection twice, 3 weeks apart. Immunogenicity was assessed on day 35 of the study. Results: A comparative immunogenicity study of naked mRNA-Vector-Flu demonstrated that both the synthesized immediately before use prepared formulation and the lyophilized form, stored at +4°C for a month, induced similar levels of virus-specific antibodies and generated a pro-nounced T-cell immune response. Conclusions: Delivery of the naked mRNA vaccine us-ing a needle-free jet injection ensures a high-level immune response, which improves its safety, reduces its cost, and eliminates the need for lipid nanoparticles traditionally used for mRNA delivery. At the same time, lyophilization of the naked mRNA vaccine pre-serves its biological activity and ensures its long-term storage at above-zero temperatures. Our results demonstrate that our proposed approach can be considered a promising di-rection for the development and improvement of the mRNA vaccine platform.

Abstract:

This study introduces the Body Heating Theory (BHT)—a physiological model explaining how controlled thermogenesis produced through brief, vigorous muscular activity can suppress viral replication and enhance immune performance. Integrating concepts from fever physiology, exercise immunology, and viral kinetics, the paper reframes body heating as a measurable, self-regulated defense mechanism rather than a secondary symptom of infection. Most respiratory viruses replicate optimally at 33–36 °C, while immune efficiency peaks between 37–39 °C. Within this narrow overlap, even a 0.5–1 °C rise in core temperature can shift the competitive balance toward the host. Early muscular activation—initiated during the first 24–48 hours after exposure—accelerates immune modulation, increases lymphatic flow, and limits viral expansion by shortening one or more replication cycles. This effect parallels the natural benefits of fever but can be safely achieved through deliberate exercise-based thermogenesis. The theory introduces a “grace period” in which temperature elevation advances immune activation ahead of viral kinetics, providing a practical rationale for early intervention. Implementation through rhythmic resistance exercise, such as IsoTone sessions, demonstrates a portable, non-pharmaceutical method for maintaining immune readiness and mitigating common colds. By linking temperature, motion, and immunity into one coherent framework, BHT positions controlled thermogenesis as a foundational element of preventive medicine and a testable model for integrating physiology, behavior, and health.

Abstract: Goose astrovirus (GoAstV) infection has become prevalent in major goose-producing regions, causing substantial economic losses to the industry. In this study, an indirect competitive ELISA (ic-ELISA) was developed based on a monoclonal antibody (mAb) targeting the GoAstV VP27 protein. The recombinant VP27 protein was expressed in E. coli and purified, followed by the generation of murine mAbs using the purified antigen. Through screening with GoAstV particles, mAb 3G11 exhibited strong immunoreactivity, which was further confirmed by Western blot and immunofluorescence assay (IFA). The ic-ELISA conditions were optimized as follows: GoAstV particle coating concentration of 10⁴ TCID₅₀ per well, 3G11 mAb dilution of 1:8000, and incubation times of 120 min for coating, 60 min for serum samples, and 60 min for mAb binding. The assay exhibited satisfactory performance in terms of sensitivity, specificity, and reproducibility. Using this method, serum samples collected from major goose farming areas in Shandong province were tested and showed an overall seropositivity rate of 11.7%. This study provided a reliable serological tool for detecting GoAstV-specific antibodies and would support future vaccine evaluation efforts.

Abstract: Climate change and the resulting abiotic stresses that emerge due to anthropogenic activities are the main causes of agricultural losses worldwide. Abiotic stresses such as water scarcity, extreme temperatures, high irradiance, saline soils, nutrient deprivation and heavy metal contamination compromise the development and productivity of crops on a global scale. In this scenario, understanding the response of C4 plants to different abiotic stresses is of utmost importance, as they constitute major pillars of the global economy. To further our understanding of the response of C4 monocots, Setaria viridis and Setaria italica have gradually emerged as powerful model species for elucidating the physiological, biochemical, and molecular mechanisms of plant adaptation to abiotic stresses. This review integrates recent findings on the morphophysiological, transcriptomic, and metabolic responses of S. viridis and S. italica to drought, elevated heat and light, saline soils, nutrient deficiencies and heavy metal contamination. Comparative analyses highlight conserved and divergent stress-response pathways between the domesticated S. italica and its wild progenitor S. viridis. Together, these findings reinforce Setaria as a versatile C4 model for unraveling mechanisms of abiotic stress tolerance and highlight its potential as a genetic resource for developing climate-resilient cereal and bioenergy crops.