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Integrating transcriptomic and metabolomic analysis in roots of wild soybean seedlings in response to low-phosphorus stress.

INTRODUCTION: Plants undergo divergent adaptations to form different ecotypes when exposed to different habitats. Ecotypes with ecological adaptation advantages are excellent germplasm resources for crop improvement. METHODS: his study comprehensively compared the differences in morphology and physiological mechanisms in the roots of two different ecotypes of wild soybean (Glycine soja) seedlings under artificially simulated low-phosphorus (LP) stress. RESULT: The seedlings of barren-tolerant wild soybean (GS2) suffered less damage than common wild soybean (GS1). GS2 absorbed more phosphorus

Integrated analysis about the effects of heat stress on physiological responses and energy metabolism in Gymnocypris chilianensis.

The temperature of the rivers in the Qilian Mountains, China varies widely from day to night, and Gymnocypris chilianensis living in these rivers may experience a change of 10 °C to 20 °C within a day. To explore the mechanisms underlying G. chilianensis responses to heat stress, we conducted an acute temperature stress experiment. In response to heat stress, levels of antioxidant enzymes (SOD\CAT\MDA) first increased and then decreased with time, but T-AOC levels only decreased. The activities of key glycolytic enzymes HK and PFK in the liver also first increased and then decreased and transa

Convergent Microglial and Astrocytic Responses across Diverse Stress Paradigms: Integrating Inflammation, Metabolism, and Behavior.

The central nervous system responds to diverse challenges through convergent glial mechanisms, yet most reviews examine single stressor paradigms in isolation. This review uniquely integrates current knowledge across five major stress categories (psychosocial, immune/inflammatory, infectious, injury/damage, and metabolic), revealing both shared pathways and stimulus-specific glial responses that have not been systematically compared. Because microglia and astrocytes are the principal immune-metabolic sensors mediating these responses, this review is centered on these two cell types, while ackn

Integrative multi-omics analysis reveals systemic and intestinal responses to heat stress in finishing pigs.

Heat stress (HS) is a major environmental threat to swine production that impairs growth performance and health. Because of their limited thermoregulatory capacity, pigs are highly vulnerable to HS, which results in compromised intestinal integrity, systemic inflammation, and metabolic inefficiency. To elucidate the mechanisms underlying HS acclimation in pigs, we conducted a longitudinal multi-omics analysis integrating fecal microbiome, whole-blood transcriptome, and immune cell deconvolution in finishing pigs under thermoneutral (TN) or HS conditions. HS markedly reduced the average daily g

Integrated Methylome and Transcriptome Analyses Reveal Methylation-Associated Cadmium Stress Responses in Sophora tonkinensis.

Cadmium (Cd) is a highly toxic heavy metal that impairs plant growth, metabolism, and the accumulation of bioactive compounds. To investigate methylation-associated Cd responses in the medicinal plant Sophora tonkinensis, we integrated whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing under three Cd treatments (T0, T2, and T4). Cd stress induced extensive transcriptional reprogramming and widespread DNA methylation changes, with CHH methylcytosines accounting for the largest proportion of methylated sites, whereas CG sites showed the highest average methylation level. Diffe

Integrative physiology, transcriptomic, and metabolomic analysis reveals the response mechanism of melon seedlings to cold stress.

Early-spring cultivation enables melons to be marketed ahead of the regular season, yet cold stress during this critical growth stage severely suppresses seedling growth and development, ultimately causing substantial yield losses. To date, the physiological shifts, molecular regulatory cascades and metabolic reprogramming triggered by cold stress in melon seedlings have not been fully characterized. In this work, we combined physiological assays, transcriptome, and metabolome profiling to dissect cold-responsive regulatory networks at the seedling stage using two melon inbred lines with diver

eIF3 Orchestrates a Biphasic Stress Response Linking Translational Control to Mitochondrial Integrity in Skeletal Muscle.

Skeletal muscle adaptation to physiological and pathological stressors requires precise coordination of protein synthesis and mitochondrial function. While the roles of canonical translation regulators such as eIF2α and 4E-BP1 in exercise-induced protein synthesis modulation are well established, the contribution of eIF3, the largest eukaryotic initiation factor complex, to muscle stress responses remains poorly understood. Eukaryotic initiation factor 3 (eIF3) regulates mRNA translation and mitochondrial homeostasis, yet how individual eIF3 subunits respond to distinct modes of skeletal muscl

Integrative Transcriptomic and Machine-Learning Analysis Reveals Immune-Inflammatory and Stress-Response Alterations in MRONJ.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predicti

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… These findings are consistent with activation of the integrated stress response (ISR). We suggest that impaired stress-handling pathways—combining altered translational control, oxidative stress, and the unfolded protein response—may worsen immune-mediated tissue injury. …

Identification and validation of prognostic genes and prognostic models associated with cutaneous melanoma and integrative stress response.

BACKGROUND: Skin cutaneous melanoma (SKCM) is a highly invasive cancer with dismal prognosis. Integrated stress response (ISR) is associated with tumorigenesis and progression, but its relationship with SKCM prognosis is unclear. This research aimed to identify relevant prognostic genes for SKCM prognosis and treatment insights. METHODS: Data were obtained from public databases. Differential expression and regression analyses were used to identify prognostic genes. Based on these genes and independent prognostic factors, risk models and nomograms were constructed to assess their clinical appl…

Role of the small GTPase Rho1 in cell wall integrity, stress response, and pathogenesis of Aspergillus fumigatus.

Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of β-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of β-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcri

Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response".

Haptoglobin (Hp) synthesis occurs almost exclusively in liver, and it is rapidly upregulated in response to stress. Because many of the pathways that initiate hepatic Hp synthesis are also operative during acute kidney injury (AKI), we tested whether AKI activates the renal cortical Hp gene. CD-1 mice were subjected to six diverse AKI models: ischemia-reperfusion, glycerol injection, cisplatin nephrotoxicity, myoglobinuria, endotoxemia, and bilateral ureteral obstruction. Renal cortical Hp gene induction was determined either 4-72 h or 1-3 wk later by measuring Hp mRNA and protein levels. Rela

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated.

Integrated Survival Assessment and mRNA/miRNA Transcriptomics Reveal Heat Stress Response and Recovery Mechanisms in Cultured Razor Clam Sinonovacula constricta.

Intertidal burrowing bivalves, such as razor clam Sinonovacula constricta, are economically significant aquaculture species in coastal China. However, they exhibit high susceptibility to heat stress under global warming, which poses a substantial challenge to aquaculture sustainability and production. While several studies have identified genes responsive to heat stress in S. constricta, the regulatory mechanisms and core networks underlying these responses remain poorly understood. Non-coding RNAs (ncRNAs) play a crucial role in gene regulation. To investigate the function of ncRNAs and their

Integrated Physiological, Transcriptomic, and Metabolomic Analyses Reveal the Mechanism Underlying the Response of Alfalfa to Combined Salt and Heat Stress.

Salt and heat stresses often occur simultaneously in arid regions, restricting the distribution and productivity of alfalfa (Medicago sativa L.). However, the mechanisms underlying alfalfa responses to combined salt and heat stress remain unclear. Here, we integrated phenotypic, physiological, transcriptomic, and metabolomic analyses to investigate the regulatory mechanisms involved in combined stress responses. Combined stress more strongly inhibited plant height, stem diameter, fresh weight, net photosynthetic rate, and transpiration rate than single stresses. Salt stress had a predominant e

Mitochondrial ROS-associated integrated stress response is involved in arsenic-induced blood-testis barrier disruption and protective effect of melatonin.

Arsenic (As) is an environmental metalloid. Previous studies have demonstrated that As exposure resulted in decline of sperm quality. This study aimed to investigate the impact of exposure to As on blood-testis barrier (BTB) in a mouse model. Four-week-old male mice were exposed to NaAsO2 (1 or 15 mg/L) for 6 weeks. Our results found that NaAsO2 exposure disrupted the BTB and reduced sperm counts in adult mice. NaAsO2 activated the integrated stress response (ISR) and downregulated barrier junction protein in mouse testes and Sertoli cells. Ribosome profiling sequencing (Ribo-seq) and Ribosome…

Chlamydia pneumoniae relies on host glutathione for its growth and induces integrated stress response-mediated changes in macrophage glutathione metabolism.

The obligate intracellular bacterium Chlamydia pneumoniae can enter into persistent phenotype, which is refractory to antibiotics and causes prolonged inflammatory state in the host. Molecular mechanisms enabling C. pneumoniae intracellular survival and governing the balance between persistent and productive infection phenotype remain poorly understood. In this study, the role of glutathione (GSH) metabolism in C. pneumoniae growth and progeny production was studied in THP-1 macrophages and A549 epithelial cells. Results indicate that depletion of cellular GSH pools decreased C. pneumoniae rep

Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.

In alcohol-associated liver disease (ALD), hepatic reductions in vitamin A and perturbations in vitamin A metabolism are common. However, th … trafficking transcripts and lower beta-oxidation transcripts. ETOH-BKO mice also exhibited a higher integrated stress response (ISR) signature, including higher transcript and protein levels of ATF4 and its target, 4-EBP1. In human hepatocytes (HepG2) that lack RARβ (RARβ-KO), ETOH treatments resulted in greater reactive oxygen species compared to their parental cells. Nota …

Response mechanism of lettuce (Lactuca sativa L.) under combined stress of Cd and DBDPE: An integrated physiological and metabolomics analysis.

DBDPE and Cd are representative contaminants commonly found in electronic waste (e-waste), which tend to be gradually discharged and accumulated in the environment during e-waste dismantling, resulting in frequent outbreaks and detection of these pollutants. The toxicity of both chemicals to vegetables after combined exposure has not been determined. The accumulation and mechanisms of phytotoxicity of the two compounds, alone and in combination, were studied using lettuce. The results showed that the enrichment ability of Cd and DBDPE in root was significantly higher than that in aerial part.

Positive Allosteric Modulation of mGlu1 Reverses Cocaine-Induced Behavioral and Synaptic Plasticity Through the Integrated Stress Response and Oligophrenin-1.

BACKGROUND: Cue-induced cocaine craving progressively intensifies (incubates) during abstinence from cocaine self-administration. Expression … cubated craving and remove CP-AMPARs from NAc synapses under control conditions, after blocking the integrated stress response (ISR), or after knocking down oligophrenin-1, a mediator of the ISR that can promote AMPAR endocytosis. AMPAR transmission in NAc medium spiny neurons was assessed with ex vivo slice recordings. RESULTS: mGlu1 stimulation reduced cue-induced cravin …

Transcriptional and metabolic remodeling in clear cell renal cell carcinoma caused by ATF4 activation and the integrated stress response (ISR).

Research has shown extensive metabolic remodeling in clear cell renal cell carcinoma (ccRCC), with increased glutathione (GSH) levels. We hypothesized that activating transcription factor-4 (ATF4) and the integrated stress response (ISR) induce a metabolic shift, including increased GSH accumulation, and that Vitamin A deficiency (VAD), found in ccRCCs, can also activate ATF4 signaling in the kidney. To determine the role of ATF4, we used publicly available RNA sequencing (RNA-seq) data sets from The Cancer Genomics Atlas. Subsequently, we performed RNA-seq and liquid chromatography-mass spect…