Molecular Response Research Articles

Water deficit is a major environmental stress significantly affecting plant growth and productivity. This research examined the molecular and biochemical responses of Scrophularia striata, a traditional Iranian medicinal plant, to drought stress. It also evaluated whether the separate and combined application of salicylic acid (SA) and silicon (Si) could alleviate these negative effects. The present study was conducted in a greenhouse with a four-factor factorial completely randomized design (FCRD) experimental design with three replications. The treatments included combinations of drought stress level 50% of field capacity (FC50%), SA at two levels (0 and 100 mg L- 1), as well as Si at two levels (0 and 1g L- 1). The evaluated biochemical parameters included β-carotene, α-tocopherol, and beta-amyrin (βA) content, as well as changes in the expression of genes involved in the terpenoid pathway. The mean comparison revealed that drought stress lowered the levels of β-carotene, α-tocopherol, and βA. This suggests that the adaptive metabolites changed in response to adverse environmental conditions. It reduced the expression of biosynthesis genes such as geranyl diphosphate synthas (GPPS), isopentenyl diphosphate isomerase (IPPI), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase (FPS), and beta-amyrin synthase (βAS). The use of SA heightened the expression of the isopentyl diphosphate isomerase gene. When salicylic acid (SA) and Si were employed together, they elevated the levels of β-carotene, α-tocopherol, and βA under FC50% drought stress conditions. The findings provide important insights into the transcriptional and metabolic reprograming of S.striata under drought stress. These results have significant implications for the development of drought-resilient of medicinal plants increasingly confronting climate changes stresses.

Background Tyrosine-kinase inhibitors (TKIs) have reshaped chronic myeloid leukemia (CML) outcomes, but real-world data from Eastern Europe remain scarce. Methods We retrospectively analyzed 201 adult patients with CML managed at the Cluj-Napoca Department of Haematology (January 2001–December 2024). A semi-automated pipeline utilizing a Large Language Model was developed to extract structured data from unstructured medical discharge report text, with all patient identifiers removed to ensure anonymity. We captured demographics, disease phase, line-specific TKI use, adverse events (AEs), treatment-free remission (TFR) eligibility, TFR attempts, continuation, laboratory data and discontinuation. Machine learning models were trained to predict TFR potential. Results Patients <60 years old, 101/201 (50.2%), and ≥60 years old, 100/201 (49.8%) were nearly equal in number. 53.7% were male. At diagnosis, 94.5% were in chronic phase. First-line treatment comprised imatinib in 108/201 (53.7%), dasatinib in 56/201 (27.9%), and nilotinib in 37/201 (18.4%). Second-line therapy ( n = 64) was dominated by dasatinib (64.1%) and nilotinib (28.1%). Third- and later-line regimens increasingly incorporated bosutinib, ponatinib, and asciminib. Fourteen patients (7.0%) achieved sustained treatment-free remission (TFR). Among these, 3 had received imatinib, 3 dasatinib, and 8 nilotinib. An additional 31 patients (15.4%) were TFR-eligible but still on therapy—16 of them after imatinib, 9 after dasatinib and 6 after nilotinib. Imatinib achieved MR4+ in 29% of exposures and nilotinib in 43.3% of third-line uses, underscoring its role as the cohort’s most effective TFR-enabler. Predictive modelling for TFR potential using a Random Forest classifier achieved high accuracy (85.4%), with top predictors being whether a patient had ever achieved a deep molecular response (achieved_mr4_ever) and the best response after the first year (best_response_after_year1), highlighting the importance of both depth and timing of molecular remission. Adverse events led to discontinuation in 17/105 imatinib (16.1%), 23/105 dasatinib (21.9%), 9/68 nilotinib (13.2%), 6/13 bosutinib (46.2%), 4/11 ponatinib (36.4%), and 2/11 asciminib (18.2%) exposures. The most common imatinib discontinuation cause was loss of therapeutic response (34/105; 32.4%). Conclusion In this Romanian center, imatinib was the predominant front-line TKI, reflecting both its earlier availability as the sole treatment option and the durable responses achieved by many long-term patients, but second-generation agents are increasingly used in over 40% of first-line starts. TFR uptake is limited despite a sizeable eligible population. Machine learning models demonstrate that both the depth and kinetics of molecular response are critical for predicting TFR potential. Prospective optimization of molecular monitoring and discontinuation protocols may broaden TFR success.

Background and Objectives: The biological behavior of gliomas is influenced by various factors including molecular features and treatment response. This study investigates the prognostic implications of a second tumor in patients with glioma at time of diagnosis. Given the increasing number of patients presenting with multiple primary malignancies due to improved cancer survival and diagnostic accuracy, understanding the influence of double tumor burden on glioma outcomes is of growing clinical relevance. Methods: We retrospectively analyzed adult patients with intracranial gliomas (WHO grade 2–4), who were surgically treated between 2015 and 2022 at our institution. Patients were categorized into two groups: glioma only and glioma plus additional solid malignancy. We compared progression-free survival (PFS) and overall survival (OS) using Kaplan–Meier and Cox regression analyses. Results: Among 426 glioma patients, 75 (17.6%) harbored a second non-brain tumor. Patients with multiple primaries showed significantly poorer OS (median 6 vs. 14 months, p = 0.002). No significant difference in PFS or OS was observed for patients in case the systemic tumor was in complete remission as compared to those with sole glioma. However, patients with progressive or stable systemic tumor had significantly worse outcomes regarding OS (p < 0.05). Conclusions: Our findings suggest that the presence of a second systemic malignancy is an independent prognostic factor for worse outcome. Further studies are mandated to elucidate genetic situations and refine therapeutic strategies for these patients.

The growing popularity of cannabis smoking in an era of legalization has prompted concerns about respiratory health. To investigate clinical and airway epithelial transcriptomic features associated with cannabis smoking. This cross-sectional study analyzed 139 cannabis-smoking participants categorized by joint-year exposure (low: ≤5; moderate: >5-20; high: >20), and 57 never-smokers. We evaluated respiratory symptom questionnaire scores, lung function measurements, and chest computed tomography and hyperpolarized 129Xe pulmonary magnetic resonance imaging measurements across groups. We compared the expression of immune response signatures and mucin genes in airway epithelial brushings collected from bronchoscopy. Using air-liquid interface (ALI) cell cultures, we quantified epithelial MUC5AC protein and correlated its expression with clinical outcomes. Among cannabis-smoking individuals (48% male and median age of 27 years), 84% reported current or former cigarette smoking or vaping. Cannabis-smoking groups reported worse respiratory symptoms than never-smokers. High joint-year cannabis-smoking participants showed lower pre-bronchodilator FEV1/FVC and FEF25-75, more radiographic emphysema, and more ventilation abnormalities than never-smokers. Airway epithelial brushings from cannabis-smoking individuals demonstrated increased type 2 immune response, decreased type 17 immune response, and higher MUC5AC gene expression than non-cannabis-smoking individuals. Epithelial MUC5AC protein expression in cell cultures correlated with worse clinical outcomes and imaging abnormalities. Cannabis smoking, particularly at high exposures, is associated with worse respiratory symptoms, lower lung function, functional imaging abnormalities, and dysregulated immune responses in the airway epithelium. These observations suggest respiratory harm associated with cannabis smoking and underscore the concerns for future respiratory morbidities related to persistent cannabis use.

Climate change is projected to increase environmental humidity in northern latitudes, yet its effects on tree hydraulics remain underexplored. We investigated how elevated air relative humidity and increased soil moisture influence water relations, gas exchange, and aquaporin (AQP) expression in silver birch (Betula pendula) at the free air humidity manipulation experiment. We applied air humidification and soil irrigation treatments and measured leaf hydraulic conductance, gas exchange parameters, and AQP transcript levels in leaves to assess physiological and molecular responses. Both treatments significantly decreased leaf hydraulic efficiency, that is the capacity of leaves to transfer water in liquid phase. However, AQP expression responded divergently: air humidification downregulated most AQP transcripts, whereas soil irrigation upregulated them. Despite these changes, gas exchange remained stable, but stomatal sensitivity to vapour pressure deficit declined under both treatments. Our findings suggest distinct regulatory mechanisms of AQPs in response to atmospheric vs edaphic moisture, while resulting in convergent physiological outcomes. The reduced stomatal sensitivity and decoupling between hydraulic performance and photosynthetic activity under nonstress conditions indicates a shift in water-use strategies and highlights the pronounced hydraulic plasticity of B. pendula. These results have implications for predicting tree and forest resilience under future climate scenarios, where increasing humidity may compromise hydraulic safety and water-use regulation during extreme weather events.

Ovarian cancer (OC) and endometrial cancer (EC) are highly heterogeneous gynecological malignancies with distinct molecular subtypes, therapeutic responses, and clinical outcomes. Traditional biopsy-based profiling often fails to capture the spatial and temporal complexity of these tumors. Radiogenomics, integrating imaging features with genomic and molecular data, has emerged as a promising approach to non-invasively analyze tumor heterogeneity. The purpose of this abstract is to critically examine and synthesize existing research on the application of radiogenomics in OC and EC, focusing on its ability to correlate imaging phenotypes with molecular biomarkers. This narrative review aims to demonstrate how radiogenomics can enhance tumor characterization, support biomarker prediction, and inform prognosis and therapeutic decision-making with non-invasive methods.This narrative review critically synthesizes current literature on radiogenomics applications in OC and EC. Studies using CT, MRI, and PET imaging were evaluated for their ability to correlate imaging phenotypes with molecular biomarkers, gene expression profiles, and clinical outcomes. The analysis emphasizes the role of radiogenomics in enhancing tumor characterization, predicting biomarker status, forecasting treatment response and prognosis.Radiogenomics has successfully identified associations between imaging features and key molecular alterations, such as BRCA mutations, homologous recombination deficiency (HRD), and immune-related biomarkers in OC, as well as POLE mutations, microsatellite instability (MSI), and tumor mutational burden (TMB) in EC. Predictive models incorporating radiomic features have demonstrated notable performance in estimating prognosis, treatment response, and recurrence risk across both cancer types.Radiogenomics has a strong potential to enhance personalized cancer care by analyzing tumor heterogeneity. However, clinical application requires methodological standardization, prospective validation, and integration into precision oncology workflows. · Radiogenomics enables non-invasive assessment of spatial and molecular heterogeneity in OC and EC.. · Integration of imaging and genomic data improves prediction of biomarkers, therapy response, and survival.. · Future clinical applications depend on methodological standardization, prospective validation, and integration into precision oncology workflows.. · Dolciami M, Celli V, Panico C et al. Unraveling Tumor Heterogeneity in Gynecological Cancer Using a Radiogenomics Approach Rofo 2025; DOI 10.1055/a-2698-8545.

Background: Heart failure (HF) involves complex interactions among cardiac cell types that drive disease progression. The neuregulin (NRG-1)/ErbB pathway is critical for cardiac repair, but clinical use of NRG-1 is limited by poor stability and receptor specificity. JK07, a fusion of an anti-ErbB3 antibody and the EGF-like domain, selectively activates ErbB4 while blocking ErbB3 activation to reduce side effects. While JK07 has demonstrated early promise in the treatment of HF clinically, its cellular mechanisms underpinning these effects remain unclear. This study explores how JK07 impact on gene expression across key cardiac cell populations. Hypothesis: We hypothesized that JK07 modulates gene expression in key cardiac cell types, inducing distinct molecular responses depending on treatment duration. Methods: BALB/c mice with MI-induced HF (EF<40%) received either a single or four weekly doses of JK07 (1 mg/kg) or vehicle. Hearts were collected 1 and 7 days after treatment for the single-dose experiments, or 7 and 28 days after the last dose for the four-dose experiments. Assessments included echocardiography, heart weight, histology, and single-nuclei RNA sequencing. Results: JK07 promoted cardiac recovery by reducing interstitial fibrosis and increasing capillary density in multi-dose groups. NT-proBNP levels decreased 7 days post-treatment in both protocols. Single-nuclei transcriptomics showed significant JK07-induced changes in cardiomyocytes, fibroblasts, macrophages, and endothelial cells, most prominently 1 and 7 days after a single dose. In cardiomyocytes, JK07 partially reversed HF-associated gene expression and enhanced mitochondrial and metabolic pathways, with confirmation in vitro via Seahorse mito stress test. In fibroblasts, JK07 altered key HF-related genes, including upregulation of Htra3 and downregulation of Igfbp7 , implicating the Htra3–TGFβ–Igfbp7 axis in antifibrotic effects. Further subclustering revealed an ErbB4-high fibroblast subtype with high expression of WNT pathway genes and potential roles in cell interactions. In endothelial cells, JK07 activated angiogenic, cytoskeletal, and repair pathways. Conclusion: JK07 promotes cardiac repair by driving cell-type-specific transcriptional programs that support metabolic adaptation in cardiomyocytes, modulate ErbB4-high fibroblast functions, and enhance endothelial regeneration. These findings highlight the therapeutic potential of JK07 as a disease-modifying agent in HF.

Background: Exercise improves cardiac health and lowers cardiovascular disease (CVD) risk, yet its protective molecular mechanisms remain incompletely understood. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) provides a multi-omic atlas of endurance exercise responses in rat tissues. We performed a sex- and time-resolved integration of heart data to identify key adaptations and their relevance to CVD prevention. Methods: We applied MEFISTO, a time-aware extension of Multi-Omics Factor Analysis (MOFA2), to integrate longitudinal MoTrPAC multi-omics data—including transcriptomics, epigenomics, proteomics, post-translational modifications, and metabolomics—collected across 1 to 8 weeks of endurance training in male and female rats. Latent factors, which summarize multi-omics features covariation, were used to identify sex-specific molecular responses to endurance exercise. These factors were compared to public CVD datasets to assess shared and divergent molecular signatures. Results: We identified six latent factors spanning at least three omics layers, including four associated with endurance training. Factors 3, 4, and 5 reflected early, sex-specific adaptations involving energy and fatty acid metabolism. Particularly, Factor 1 captured a progressive, sex-shared signature, strongly correlated with VO2max (r > 0.8, p < 1e–6; Figure 1). This factor reflected a shift from acute metabolic responses to long-term remodeling, with upregulation of ATP metabolism, cardiac morphogenesis, and contractility pathways, supported by epigenetic and post-translational regulation (Figure 2). These findings suggest that endurance exercise enhances mitochondrial efficiency and promotes cardiac tissue maturation. Comparison with human CVD signatures revealed significant inverse enrichment in ischemic heart disease (p < 2e–10), heart failure (p < 2e–3), and cardiac hypertrophy (p < 6e–4). Genes associated with Factor 1 and inversely linked to CVD signatures were enriched for reduced T cell immunity and increased extracellular matrix organization, highlighting a coordinated immunomodulatory and structural adaptation. Conclusion: Endurance exercise drives sustained molecular remodeling, shifting from early metabolic activation to enhanced mitochondrial efficiency, epigenetic regulation, and cardiac development. Its inverse association with CVD signatures highlights exercise’s protective role through immune modulation and structural remodeling of the heart.

Clinical case reports in oncology are an untapped resource of patient data that include relationships between molecular alterations, tumor types, and response to targeted therapy. A current challenge to widespread utilization of case reports in clinical practice is the lack of systematic organization of clinical evidence across disease types, patient outcomes, therapies, and associated molecular features. To address this challenge, we sought to demonstrate the utility of Cancer Knowledgebase (CKB) (https://ckb.genomenon.com/) in interpreting oncology case report data for health care providers. We analyzed data from 5527 manually curated case reports in CKB to gain insights related to treatment options and patient response associated with specific molecular alterations. Each case report in CKB is represented as a unique efficacy evidence annotation and is associated with a specific molecular profile, therapy, indication, and response to therapy. Efficacy evidence from case reports spans over 500 genes, 2800 molecular profiles, and 300 tumor types, including several rare cancers and pediatric tumor types. CKB is a powerful resource for leveraging case reports to identify treatment options for patients with rare cancers and oncogenic variants, patients for whom multiple therapies exist, and patients experiencing resistance to first-line therapy.

This study evaluated the physiological, biochemical traits, molecular responses, and vase life of cut Alstroemeria hybrida ‘Amatista’ in response to preharvest applications of putrescine and melatonin. A factorial experiment was arranged in a completely randomized design with three replications. The treatments included foliar sprays of putrescine (0, 1.5, and 3 mM), melatonin (0, 50, and 100 µM), and four postharvest sampling times (0, 5, 10, and 15 days). Measured parameters included chlorophyll index, relative fresh weight, solution uptake, ion leakage, malondialdehyde (MDA), hydrogen peroxide (H2O2), polyphenol oxidase (PPO) activity, vase life, and the relative expression of chlorophyllase (CHL) and ACC oxidase (ACO) genes. Postharvest senescence was associated with a time-dependent decline in chlorophyll index, water content, and solution uptake, along with increased ion leakage, MDA, H₂O₂ levels, and PPO activity. However, preharvest application of putrescine and melatonin effectively delayed these detrimental changes. Notably, the combined application of 1.5 mM putrescine and 50 µM melatonin resulted in the greatest improvement in postharvest performance, extending vase life from 16.00 to 23.66 days and enhancing physiological and biochemical traits. Moreover, gene expression analysis indicated that these treatments suppressed the expression of CHL and ACO, suggesting a molecular mechanism involved in delayed senescence. Overall, the findings highlight the potential of putrescine and melatonin as eco-friendly preharvest treatments to improve the postharvest quality and longevity of cut Alstroemeria flowers by modulating key physiological, biochemical, and molecular processes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12870-025-07530-6.

Traumatic brain injury (TBI) affects millions of people globally each year, yet effective treatments remain limited. A major challenge is the complexity of cellular and molecular responses to brain injury, many of which overlap with those seen in aging. A key hallmark of aging is nucleolar enlargement in brain and other tissues, reflecting increased ribosome biogenesis. Nucleolar size is regulated by the target of rapamycin (TOR) signaling pathway, which during aging is aberrantly activated. Inhibiting TOR reduces nucleolar size and extends lifespan in several model organisms. Using a Drosophila melanogaster model of closed-head TBI, we investigated whether injury influences nucleolar dynamics. Immunofluorescence microscopy of fibrillarin, a major nucleolar protein, revealed that brains of young, injured flies had substantially larger nucleoli than uninjured controls within one day of injury. Over the following weeks, the difference gradually diminished as nucleolar size increased in uninjured flies, eventually matching that of injured flies, which remained relatively stable. Additionally, heterogeneity in nucleolar size across cells became more pronounced with injury and aging. Finally, injury of older flies resulted in little or no nucleolar enlargement and even shrinkage within a few days of injury. These results suggest that TBI and aging converge on shared mechanisms that regulate nucleolar size, which may reach a maximal limit through either process. Consistent with this, mortality at 24 hours post-injury in young flies was significantly reduced by pharmacological inhibition of TOR with rapamycin or RapaLink-1, indicating that nucleolar enlargement contributes to TBI-induced damage. Overall, our results suggest that TBI accelerates the aging-associated increase in nucleolar size, implicating elevated ribosome biogenesis in TBI pathogenesis and highlighting TOR inhibition as a promising therapeutic approach.

ABSTRACT Diquat is used in agriculture as an herbicide but poses significant health risks upon exposure. Current treatment for toxic exposures to diquat focuses on supportive care, and there is a need for better understanding of the molecular mechanisms underlying diquat-induced injury in order to develop more targeted antidotes. To this end, TAMH cells were exposed to various concentrations of diquat to determine toxicologically relevant concentrations followed by subsequent transcriptomic analysis. Data mining from the MAQC-II dataset, which was accessed through the Gene Expression Omnibus (GEO) was also leveraged during the gene network analysis. A median lethal concentration (LC50) for diquat in the TAMH line was determined to be 18 μM, with significant cell death observed at 9 hours. Microarray data identified 3,578 significantly altered transcripts in the TAMH model and 6,554 from the MAQC-II dataset, with notable overlap in gene expression changes. Pathway analysis using DAVID highlighted MAPK signaling as playing a role during diquat-induced toxicity in both models, with 11 shared transcripts suggesting a conserved molecular response across rodent species. This study aimed to investigate the molecular mechanisms behind diquat-induced toxicity using TAMH cells and identified MAPK signaling pathway as involved. By demonstrating the utility of combining GEO and DAVID for pathway analysis, this study not only highlights potential therapeutic targets for diquat toxicity but also presents a broadly applicable, cost-effective strategy for toxicogenomic research.

BackgroundRapid and efficient epithelial regeneration is fundamental for tissue homeostasis and proper function. As the outermost ocular structure, the cornea is transparent, multilayered, and vital for clear vision. Due to its exposed position, the cornea frequently undergoes various forms of injury affecting either the epithelium itself or its surrounding microenvironment, including corneal innervation and the tear film. Corneal abrasion, occurring commonly through trauma or as part of refractive surgical procedures, is typically viewed as a minor event since it usually resolves rapidly. Consequently, the cornea serves as an excellent model for studying epithelial wound healing. However, complications such as persistent epithelial defects or corneal opacity can develop, underscoring critical gaps in understanding the underlying molecular mechanisms.MethodsUtilizing a unilateral corneal abrasion mouse model, we conducted a comprehensive multi-omics analysis, integrating transcriptomics, proteomics, and epitranscriptomics, to dissect the dynamic molecular responses post-injury in both wounded and contralateral tissues. To elucidate the role of the tear film, we performed additional studies involving lacrimal gland ablation combined with corneal injury. We applied RNA sequencing to profile transcriptomic changes in corneal and lacrimal gland tissues, and mass spectrometry to study tear proteomics and epitranscriptomic modifications.ResultsWe revealed a major modulation of the cornea transcriptome after abrasion, suggesting a regulation of pathways including JAK-STAT, Wnt and TGF-β, and a reduction of nucleoside modifications. The lacrimal gland transcriptome and tears proteome were also significantly affected. Plus, we highlighted a bilateralization, both in the cornea transcriptome and tears proteome. In the tear-deficient conditions, the wound closure rate and molecular responses were altered, and the bilateralization was impacted, with an increased matrix remodeling and a modulation of keratins expression.ConclusionsOur multi-omics analyses revealed extensive epithelial cellular plasticity as a key mechanism driving rapid wound closure, characterized by profound remodeling of transcriptional networks and RNA modifications. Importantly, we uncovered a previously underappreciated role of the lacrimal gland and tear film in mediating bilateral molecular responses following unilateral injury, emphasizing their pivotal roles in tissue regeneration. Additionally, we identified novel regulatory roles for RNA methylation events and critical signaling pathways implicated in epithelial healing.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s11658-025-00804-9.

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that interfere with hormonal signaling and compromise reproductive success in aquatic organisms. Vitellogenin (VTG) is one of the most widely established biomarkers of estrogenic exposure, especially in males and juveniles. However, evidence from multi-omics studies indicates that VTG induction occurs within broader transcriptional and regulatory networks, involving genes such as cyp19a1 (aromatase), cyp1a (cytochrome P4501A), and other stress-responsive genes, underscoring the complexity of endocrine disruption. This review focuses on nuclear receptor isoforms, including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR) variants. We examine the diversification of vtg gene repertoires across teleost genomes and epigenetic mechanisms, such as DNA methylation and microRNAs, that modulate sex-dependent sensitivity. In addition, we discuss integrative approaches that combine VTG with transcriptomic, epigenetic, and histological endpoints. Within the Adverse Outcome Pathway (AOP) and weight-of-evidence (WoE) frameworks, these strategies provide mechanistic links between receptor activation and reproductive impairment. Finally, we outline future directions, focusing on the development of sex-specific biomarker panels, the integration of omics-based data with machine learning, and advances in ecogenomics. Embedding molecular responses into ecological and regulatory contexts will help bridge mechanistic insights with environmental relevance and support sustainability goals such as SDG 14 (Life Below Water).

Traditional research in plant stress biology has predominantly focused on physiological and molecular response mechanisms under single stressors [...]

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced non-small cell lung cancer (NSCLC). Quantitative monitoring of disease burden may prove predictive in these cases. We hypothesised that serial ctDNA molecular response assessment may be predictive of response to nivolumab. 44 NSCLC patients who received nivolumab were included. All the patients underwent response assessment by RECIST every four cycles. Peripheral blood samples were obtained at baseline and after four cycles of therapy, and the quantification of ctDNA was performed by qubit dsDNA HS assay. A variant allele fraction (VAF) of >0.3% was considered to be used for tracking. A cut-off change of 50% in VAF and ctDNA was considered for molecular response. Radiological evaluations were performed at baseline and every four cycles as per RECIST 1.1 criteria. The median ctDNA concentration was higher in patients with time to progression (TTP) of <4 months (P = 0.05). Detectable alterations with >0.3% VAF were detected in 31 patients, and a molecular response of >50% was observed in patients with PR, stable disease (SD) and two patients with PD. The patients with <50%molecular response had a median PFS of 3.9 months vs. those with >50% had a median of 5.8 months (P = 0.06). A cut of 0.3 ng/microlitre baseline ctDNA concentration was predictive of PFS. This is an initial experience from India using liquid biopsy next-generation sequencing (NGS) for dynamic monitoring in immunotherapy-treated patients. A 50% cut-off for response as well as a baseline ctDNA 0f 0.3 ng/microlitre showed a trend for better PFS in these patients. This study highlights the need for serial monitoring. To our knowledge, this is among the first real-world Indian studies validating serial NGS-based ctDNA monitoring in immunotherapy-treated NSCLC. It demonstrates feasibility, predictive value, and real-world applicability in a lower-middle-income context.

Substantiating chemical groups for read-across using molecular response profiles.

Mechanisms of cellular and molecular responses in Mytilus galloprovincialis exposed to human pharmaceuticals ibuprofen, paroxetine and their mixture.

Drought is a major abiotic constraint that limits plant growth and productivity worldwide. To cope with water scarcity, plants employ complex adaptive strategies, with stomatal regulation serving as a central mechanism for balancing water conservation and photosynthetic efficiency. Phytohormones are crucial signaling mediators in this process, coordinating the molecular, physiological, and biochemical responses that govern stomatal dynamics during drought. Abscisic acid (ABA) is the principal regulator of drought-induced stomatal closure; however, other hormones, including salicylic acid, methyl jasmonates, ethylene, gibberellins, cytokinins, and auxins, modulate stomatal function through synergistic or antagonistic interactions. Such hormonal crosstalk shapes guard cell sensitivity to ABA, regulates ion channel activity, influences transcriptional networks, and ultimately determines water-use efficiency. While earlier reviews have addressed the broader roles of phytohormones in drought adaptation, they often overlook the nuanced regulation of stomatal behavior. This review uniquely synthesizes recent advances in phytohormone signaling networks, with particular emphasis on their synergistic and antagonistic crosstalk and downstream signaling cascades that govern stomatal regulation under drought stress. It further integrates current insights into hormone-mediated adaptive responses coordinated with stomatal dynamics, establishing a mechanistic framework that links molecular signaling with physiological regulation and drought tolerance. We also highlight emerging strategies to harness hormonal regulation to enhance drought resilience and outline key research priorities for translating these insights into crop improvement.

The source of nitrogen conditions transcriptomic responses to water deficit in common bean roots.