Molecular Response Research Articles

Large cell lymphoma through a liquid lens.

Liquid biopsy to provide a mutational snapshot of diffuse large B-cell lymphoma is an emerging technology of exciting potential utility. The report by Alcoceba etal. assesses the tractability of the EuroClonality-NDC assay to profile lymphoma using cell-free DNA and highlights the prognostic implication of attaining a major molecular response to therapy. Commentary on: Alcoceba etal. Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease. Br J Haematol 2024;205:109-121.

Convergent and divergent transcriptional reprogramming of motor and sensory neurons underlying response to peripheral nerve injury

IntroductionMotor neurons differ from sensory neurons in aspects including origins and surrounding environment. Understanding the similarities and differences in molecular response to peripheral nerve injury (PNI) and regeneration between sensory and motor neurons is crucial for developing effective drug targets for CNS regeneration. However, genome-wide comparisons of molecular changes between sensory and motor neurons following PNI remains limited. ObjectivesThis study aims to investigate genome-wide convergence and divergence of injury response between sensory and motor neurons to identify novel drug targets for neural repair. MethodsWe analyzed two large-scale RNA-seq datasets of in situ captured sensory neurons (SNs) and motoneurons (MNs) upon PNI, retinal ganglion cells and spinal cord upon CNS injury. Additionally, we integrated these with other related single-cell level datasets. Bootstrap DESeq2 and WGCNA were used to detect and explore co-expression modules of differentially expressed genes (DEGs). ResultsWe found that SNs and MNs exhibited similar injury states, but with a delayed response in MNs. We identified a conserved regeneration-associated module (cRAM) with 274 shared DEGs. Of which, 47% of DEGs could be changed in injured neurons supported by single-cell resolution datasets. We also identified some less-studied candidates in cRAM, including genes associated with transcription, ubiquitination (Rnf122), and neuron-immune cells cross-talk. Further in vitro experiments confirmed a novel role of Rnf122 in axon growth. Analysis of the top 10% of DEGs with a large divergence suggested that both extrinsic (e.g., immune microenvironment) and intrinsic factors (e.g., development) contributed to expression divergence between SNs and MNs following injury. ConclusionsThis comprehensive analysis revealed convergent and divergent injury response genes in SNs and MNs, providing new insights into transcriptional reprogramming of sensory and motor neurons responding to axonal injury and subsequent regeneration. It also identified some novel regeneration-associated candidates that may facilitate the development of strategies for axon regeneration.

Transcriptome analysis of Candida albicans planktonic cells in response to plasma medicine.

Introduction. Cold plasma is frequently utilized for the purpose of eliminating microbial contaminants. Under optimal conditions, it can function as plasma medicine for treating various diseases, including infections caused by Candida albicans, an opportunistic pathogen that can overgrow in individuals with weakened immune system.Gap Statement. To date, there has been less molecular study on cold plasma-treated C. albicans.Research Aim. The study aims to fill the gap in understanding the molecular response of C. albicans to cold plasma treatment.Methodology. This project involved testing a cold plasma generator to determine its antimicrobial effectiveness on C. albicans' planktonic cells. Additionally, the cells' transcriptomics responses were investigated using RNA sequencing at various treatment durations (1, 3 and 5 min).Results. The results show that our cold plasma effectively eliminates C. albicans. Cold plasma treatment resulted in substantial downregulation of important pathways, such as 'nucleotide metabolism', 'DNA replication and repair', 'cell growth', 'carbohydrate metabolism' and 'amino acid metabolism'. This was an indication of cell cycle arrest of C. albicans to preserve energy consumption under unfavourable conditions. Nevertheless, C. albicans adapted its GSH antioxidant system to cope with the oxidative stress induced by reactive oxygen species, reactive nitrogen species and other free radicals. The treatment likely led to a decrease in cell pathogenicity as many virulence factors were downregulated.Conclusion. The study demonstrated the major affected pathways in cold plasma-treated C. albicans, providing valuable insights into the molecular response of C. albicans to cold plasma treatment. The findings contribute to the understanding of the antimicrobial efficiency of cold plasma and its potential applications in the field of microbiology.

Transcriptome Analysis Reveals the Potential Key Genes in Nutritional Deposition in the Common Carp (Cyprinus carpio).

The common carp (Cyprinus carpio) is one of the most important aquaculture species in China, known for its remarkable adaptability and nutritional profile. However, the specific molecular response mechanisms regulating the nutritional deposition of carp remain inadequately elucidated. This study conducted a comprehensive analysis of muscle nutritional content and transcriptome data from liver and muscle tissues of three distinct carp varieties. The aim was to elucidate the key genes and signaling pathways that regulate muscle nutritional composition in carp. The findings revealed that FFRC carp (FFRC) exhibited significantly higher levels of crude fat, total n-3 polyunsaturated fatty acids, and total n-6 polyunsaturated fatty acids in muscle tissue compared to Ying carp (YC) and Huanghe carp (HC) (p < 0.05). Transcriptomic analyses correlated these elevated levels with a marked upregulation of genes involved in the activation and transportation of fatty acid (fabp7, acsl5, acsbg2) as well as biosynthesis and elongation of long-chain unsaturated fatty acids (elovl2, fads2) within the liver. Furthermore, the flavor amino acid, essential amino acids, and crude protein content in the muscle of HC were significantly higher than in FFRC and YC (p < 0.05). Transcriptomic analyses indicated that this was associated with significant changes in the expression of genes related to amino acid metabolism (asns, alt, ldha, glul, setd, prodh, l3hypdh, hoga1) within their muscle tissue. This research provides a theoretical foundation for the precise modulation of the muscle nutritional composition in carp.

Investigating the Diversity in Physiological, and Molecular Responses of Wheat (Triticum aestivum L.) Genotypes under Cadmium Stress

Heavy metal toxicity is a real threat to the environment, crop productivity, and the health of humans and their animals, especially when the toxicity enters the food chain. This study investigates the effect of cadmium on the physiological and molecular levels of ten introduced wheat genotypes. Genotypes were stressed by cadmium (75 mg.L-1) in comparison with unstressed treatment to highlight their response to the cadmium. The experiment was laid out as a factorial arrangement in RCBD, with three replicates. The genotypes included in this study varied in their response to cadmium stress during the laboratory tests. Notably, genotype G-41 was superior to the rest of the genotypes in terms of seed vigor (18.58), chlorophyll content (8.72 mg.g-1), and carotenoid content (4.87 mg.g-1), while genotype IRAQ had wider epidermis in the root (2.28 µm) and ordinary epidermis cells (3.10 µm). Cadmium boosted some physiological and anatomical traits (e.g., REC, Chlorophyll, carotenoids, length and width of root epidermis cells). However, cadmium concentration caused a deterioration in some anatomical traits, including cortex thickness and the length of the ordinary epidermis cells. Some wheat genotypes showed more resistance to cadmium stress than others, and G-3 was notably affected by cadmium treatment and this was associated with the high PCS1 expression of the enzyme that chelates Cd to the vacuole (39 folds). It can be concluded that cadmium reduced the physiological performances except for some genotypes that showed more tolerance. Those genotypes could therefore be investigated further to assess the accumulation of cadmium in their grains.

A Comprehensive Analysis of Drought Stress Responses in Rice (Oryza sativa L.): Insights into Developmental Stage Variations from Germination to Grain Filling

Rice (Oryza sativa L.) is a critical staple food crop vulnerable to drought stress at key growth stages, namely the early seedling stage, vegetative phase, anthesis (reproductive stage), and grain ripening stage. The impact of drought stress on rice extends beyond mere water deficit, influencing a spectrum of morphological, physiological, biochemical, and molecular responses crucial for plant survival and productivity. This review synthesizes current understanding of rice responses to drought stress across its developmental stages, encompassing seed germination, seedling establishment, vegetative growth, reproductive development, and grain filling. Drought stress triggers multifaceted adaptations in rice, involving mechanisms such as escape, avoidance, tolerance, and recovery strategies to mitigate water scarcity effects. These responses are finely tuned across developmental stages, influencing traits like root architecture, stomatal conductance, photosynthetic efficiency, osmotic adjustment, and hormonal regulation. Understanding these responses is pivotal for enhancing rice resilience to drought, thereby safeguarding global food security and supporting the livelihoods of rice-dependent communities worldwide, particularly in regions like India where rice cultivation plays a crucial socioeconomic role. Challenges persist in deciphering the complex genetic and physiological networks underpinning drought responses in rice. Integrating omics approaches and advanced phenotyping techniques holds promise in unraveling these complexities and identifying genetic markers for drought tolerance. Furthermore, strategies such as breeding resilient cultivars and implementing agronomic practices tailored to specific growth stages are imperative for sustainable rice production under increasingly erratic climatic conditions. This review consolidates existing knowledge while highlighting gaps in current understanding, aiming to guide future research endeavors toward innovative solutions for enhancing rice drought resilience. By elucidating the intricate mechanisms governing rice responses to drought stress, this study contributes to the broader discourse on agricultural sustainability and climate change resilience in staple food crops.

Spectroscopy in Nanoscopic Cavities: Models and Recent Experiments.

The ability of nanophotonic cavities to confine and store light to nanoscale dimensions has important implications for enhancing molecular, excitonic, phononic, and plasmonic optical responses. Spectroscopic signatures of processes that are ordinarily exceedingly weak such as pure absorption and Raman scattering have been brought to the single-particle limit of detection, while new emergent polaritonic states of optical matter have been realized through coupling material and photonic cavity degrees of freedom across a wide range of experimentally accessible interaction strengths. In this review, we discuss both optical and electron beam spectroscopies of cavity-coupled material systems in weak, strong, and ultrastrong coupling regimes, providing a theoretical basis for understanding the physics inherent to each while highlighting recent experimental advances and exciting future directions.

Identification of host immune-related biomarkers in active tuberculosis: A comprehensive analysis of differentially expressed genes

Tuberculosis (TB) is a serious public health issue in India. Numerous molecular mechanisms and immunological responses play significant roles in the pathogenesis of tuberculosis. This study aimed to identify host immune-related biomarkers that are significantly differentially expressed in active TB and that play a vital role in disease progression. The methodology employed in this study included data collection, pre-processing, analysis, and interpretation of the results. Six microarray datasets were used to identify differentially expressed genes (DEGs), and only the common DEGs were used for further downstream analysis, such as hub gene identification, gene ontology, pathway enrichment analysis, and drug-gene interaction analysis. The study identified 1728 DEGs, including 906 upregulated and 822 downregulated genes. Five hub genes were identified that were: STAT1, GBP5, GBP1, FCGR1A, and BATF2. Gene ontology and pathway enrichment revealed that most of the genes were involved in interferon-gamma signaling. In addition, through drug-gene interactions, known drugs have been identified for STAT1, FCGR1A and GBP1. The findings of this study may contribute to early detection and treatment of active TB.

Determination of anthracnose (Colletotrichum fructicola) resistance mechanism using transcriptome analysis of resistant and susceptible pear (Pyrus pyrifolia)

BackgroundAnthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the molecular response to anthracnose in pears.ResultsIn this study, the anthracnose-resistant variety ‘Seli’ and susceptible pear cultivar ‘Cuiguan’ were subjected to transcriptome analysis following C. fructicola inoculation at 6 and 24 h using RNA sequencing. A total of 3186 differentially expressed genes were detected in ‘Seli’ and ‘Cuiguan’ using Illumina sequencing technology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the transcriptional response of pears to C. fructicola infection included responses to reactive oxygen species, phytohormone signaling, phenylpropanoid biosynthesis, and secondary metabolite biosynthetic processes. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway and phenylpropanoid biosynthesis were involved in the defense of ‘Seli’. Furthermore, the gene coexpression network data showed that genes related to plant–pathogen interactions were associated with C. fructicola resistance in ‘Seli’ at the early stage.ConclusionOur results showed that the activation of specific genes in MAPK, calcium signaling pathways and phenylpropanoid biosynthesis was highly related to C. fructicola resistance in ‘Seli’ and providing several potential candidate genes for breeding anthracnose-resistant pear varieties.

Safety and efficacy of flumatinib as later-line therapy in patients with chronic myeloid leukemia.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

Management of Chronic Myeloid Leukemia that is Intolerant or Resistant to Front-Line Treatment

With advances in treatment for chronic myeloid leukemia (CML), the natural history of chronic phase (CP) CML has changed, with most individuals expected to live a normal life expectancy. The goal of therapy for most is to achieve a long-term deep molecular response (DMR) with the potential for medication discontinuation and treatment-free remission (TFR).1 Currently, six oral therapies have been approved for CP-CML in Canada: (1) imatinib, a first-generation tyrosine kinase inhibitor (TKI); (2) dasatinib, (3) nilotinib, and (4) bosutinib, the second-generation TKIs (2G-TKIs); (5) ponantinib, a third-generation TKI; and (6) asciminib, specifically targeting the ABL Myristoyl pocket (STAMP) inhibitor. Classically, treatment for CP-CML has consisted of front-line imatinib and switching to a 2G-TKI upon treatment resistance or intolerance. Increasingly, patients are being prescribed an upfront 2G-TKI with the goal of achieving quicker and deeper molecular remissions and a TFR.2 Challenges arise in CML when treatment with either two TKIs (imatinib + 2G-TKI) or one 2G-TKI fails, given the lack of evidence to inform clinical decision-making at this juncture. This paper aims to define TKI failure and help guide the selection of second-line treatment after failure of front-line therapy.

Analysis of the pharmacoeconomic effectiveness of the tyrosine kinase inhibitors therapy in patients with chronic myeloid leukemia in a Single Hematology Center in Plovdiv, Bulgaria

Summary: Chronic myelogenous leukemia (CML) is a pluripotent hemopoietic stem cell malignancy characterized by the presence of a BCR-ABL1 fusion gene derived from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22) (q34; q11)] known as the Philadelphia (Ph) chromosome. CML is an acquired hematopoietic stem cell disease common to myelo- and lymphopoiesis, characterized by uncontrolled proliferation of granulopoiesis (Shuvaev et al. 2015; Yordanov and Varbanova 2019). Relevance and goals: Second-generation tyrosine kinase inhibitors (TKIs) (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in the frequency and speed of achieving cytogenetic and molecular responses in the treatment of chronic myelogenous leukemia (CML), but they cause severe adverse effects and are much more expensive than imatinib, especially if we compare them to the prices of the registered generic products of Imatinib and Dasatinib. “Novartis Tasigna® trial shows superior results to Glivec® in patients with early-stage chronic myeloid leukemia”, reported on 10/20/2021 by Pierre Perrin-Montlouis. In the first direct comparison of these two oral therapies back in 2009 (Тasigna (nilotinib) 2009), as first-line treatment for CML, the results of Tasigna showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blast phase, with responses achieved faster in the Tasigna group than in the Glivec group. Furthermore, in the last ten years, CML patients who have achieved a stable deep molecular response for at least 2 years have been included in clinical trials for the management of treatment-free remission (TFR) (Kim et al. 2013; Saußele et al. 2016). On the other hand, the ever-increasing costs of diagnosis, treatment and monitoring of the response of CML to the various therapeutic strategies require conducting pharmacoeconomic analyses of the cost-effectiveness and cost-utility types in order to evaluate which are the cost-effective strategies with a view to introducing them into therapeutic practice. The present study aims to analyze the pharmacoeconomic efficiency of the TKI inhibitors used by the patients with CML-CP in the first and second lines, treated in the hematology clinic at UMHAT “St. George”, MU- Plovdiv during the period 2018–2022. Methods: An economic analysis of the medicinal use of TKIs for a 5-year period (2018–2022) was performed at the national level according to data from the National Health Insurance Fund and the availability, accessibility, and usability of original and generic TKIs in Bulgaria were evaluated. The direct medical costs for the therapy of all patients were calculated, including the costs of the TKI therapy, laboratory tests, and monitoring of the molecular response for the entire treatment period from the appointment of the TKI therapy until the end of 2022. A comparative analysis was conducted to assess the cost-effectiveness of the different therapeutic strategies with TKIs on the first and second lines of treatment of patients with CML-CP in the hematology clinic at UMHAT “St. George” Medical University, Plovdiv, using the decision analysis method and conducting one-way and probalistic sensitivity analyses. Results: The sensitivity analyzes of all pharmacoeconomic models showed the robustness and reliability of the obtained results. The threshold limits of medical costs and the frequency of achieving a deep molecular response determining the choice of first- and second-generation tyrosine kinase inhibitors as first- and second-line therapy for patients with chronic myeloid leukemia in the chronic phase have been determined. Prescribing doctors prefer the original MPs to generic analogues, which is also assumed by the current regulations, according to which even for expensive MPs dispensing by protocols, the prescription is by trade and not by international non-proprietary names (INN), which is why the use of the much cheaper generic MPs is negligibly low compared to original MPs. A personalized approach to the patient’s therapy and monitoring the patient’s molecular response to it, as well as stopping therapy in 25–30% of patients suitable to stop it safely when in TFR phase with a probability of more than 50% of not having a relapse will save additional costs that, by improving the cost-effectiveness of therapy for patients with CML, will be directed towards the treatment of new patients with this or other diseases. Conclusion: These pharmacoeconomic models can be applied to improve diagnostic and therapeutic standards in clinical practice and for the efficient use of the very limited resources for health care in countries like Bulgaria. The conducted cost-effectiveness analyses confirmed that the hematologists at the University Center in Plovdiv adhere to the recommendations of Leukemia Net and the Bulgarian Medical Society of Hematology and achieve not only good therapeutic but also pharmacoeconomic efficiency in the treatment of CML-СР patients in first- and second- line therapy.

Drought-induced molecular changes in crown of various barley phytohormone mutants

ABSTRACT One of the main signal transduction pathways that modulate plant growth and stress responses, including drought, is the action of phytohormones. Recent advances in omics approaches have facilitated the exploration of plant genomes. However, the molecular mechanisms underlying the response in the crown of barley, which plays an essential role in plant performance under stress conditions and regeneration after stress treatment, remain largely unclear. The objective of the present study was the elucidation of drought-induced molecular reactions in the crowns of different barley phytohormone mutants. We verified the hypothesis that defects of gibberellins, brassinosteroids, and strigolactones action affect the transcriptomic, proteomic, and hormonal response of barley crown to the transitory drought influencing plant development under stress. Moreover, we assumed that due to the strong connection between strigolactones and branching the hvdwarf14.d mutant, with dysfunctional receptor of strigolactones, manifests the most abundant alternations in crowns and phenotype under drought. Finally, we expected to identify components underlying the core response to drought which are independent of the genetic background. Large-scale analyses were conducted using gibberellins-biosynthesis, brassinosteroids-signaling, and strigolactones-signaling mutants, as well as reference genotypes. Detailed phenotypic evaluation was also conducted. The obtained results clearly demonstrated that hormonal disorders caused by mutations in the HvGA20ox2, HvBRI1, and HvD14 genes affected the multifaceted reaction of crowns to drought, although the expression of these genes was not induced by stress. The study further detected not only genes and proteins that were involved in the drought response and reacted specifically in mutants compared to the reaction of reference genotypes and vice versa, but also the candidates that may underlie the genotype-universal stress response. Furthermore, candidate genes involved in phytohormonal interactions during the drought response were identified. We also found that the interplay between hormones, especially gibberellins and auxins, as well as strigolactones and cytokinins may be associated with the regulation of branching in crowns exposed to drought. Overall, the present study provides novel insights into the molecular drought-induced responses that occur in barley crowns.

Integrated assessment of trace elements in a marine ranching area based on multi-species and multi-level biomarkers: a case study in China’s national-level marine ranching demonstration area

The goal of this study was to evaluate the trace element pollution in a marine ranching area in China based on molecular responses (expression of metallothionein and antioxidant enzyme genes), and biochemical biomarkers (metallothionein content, antioxidant enzyme activities, and malonaldehyde level) in four indicator species. We collected samples of two fish (Lateolabrax maculatus and Sebastes schlegelii), one crustacean (Charybdis japonica), and one gastropod (Rapana venosa) from the western Furong Island marine ranching area and from an adjacent area in March 2022 and measured the trace element content in these indicator species as well as in the seawater and sediment. We found that the bioaccumulation characteristics of trace elements and the response patterns of biomarkers were species specific. Moreover, not every biomarker was significantly correlated with environmental trace element content. We then established two biomarker combinations indicative of trace element pollution in seawater and sediment, respectively, based on the correlation between biomarkers and trace element contents. The selected biomarkers were integrated using integrated biomarker response version 2 (IBRv2). IBRv2 values in the studied marine ranching area were lower than those in the adjacent area. Additionally, these values were consistent with the bioaccumulation of trace elements in the indicator species, the integrated trace element pollution index for seawater, and the potential risk index for sediment. These results show that this multi-biomarker and multi-species IBRv2 approach provided a comprehensive diagnosis of trace element pollution in the marine ranching area. Therefore, its application may be beneficial for marine environmental monitoring and management in view of the ecotoxicological impact of pollutants on organisms.

The Impact of Early Growth Response 1 (Egr1) on Hippocampal Synaptic Plasticity and Cognitive Function: Narrative Review

Introduction: EGR1 (Early Growth Response 1) gene expression is a molecular response that occurs in the brain as a result of synaptic activity and environmental stimuli. Early growth response 1 (EGR1) expression can be affected by several factors, including exercise or physical training. This review aims to determine the effect of EGR 1 expression on hippocampal synaptic plasticity function. Method: Literature search using data-based Pubmed, Science Direct, and Scopus online. The data used is from the year 1978 until the year 2022. Searched using English keywords such as EGR 1 and hippocampus. Results: Animal and human studies show that physical exercise can increase the expression of the EGR1 gene in the brain. This enhanced EGR1 expression is associated with increased synaptic plasticity, which includes changes in the strength and connectivity of synapses between neurons. Synaptic plasticity refers to the ability of the nervous system to change the strength and efficiency of communication between neurons. Physical exercise has been shown to increase synaptic plasticity by increasing dendritic growth and continuity, increasing neurogenesis (the formation of new neurons), and increasing synaptic connections between neurons. Physical exercise can increase EGR1 expression and synaptic plasticity. Increased EGR1 expression and synaptic plasticity induced by physical exercise are associated with improvements in cognitive functions, including memory, learning, and thinking ability. Conclusion: There is evidence that exercise can increase EGR1 expression and synaptic plasticity in the brain, especially in the hippocampus, to improve cognitive function.

24-epibrassinolide as a multidimensional regulator of rice (Oryza sativa) physiological and molecular responses under isoproturon stress

Brassinosteroids (BRs) can regulate various processes in plant development and defense against environmental stress. In this study, the contribution of BRs in the degradation of isoproturon (IPU) in rice has been established. IPU has a significant effect on rice growth, chlorophyll content, and membrane permeability. When treated with 1.0 μmol/L 24-epibrassinolide (EBR), a BR analogue, the associated symptoms of rice poisoning were alleviated as the IPU levels in the rice and growth media were decreased. In the presence of EBR, the activities of several IPU-related detoxification enzymes were enhanced to cope with the stress due to IPU. An RNA-sequencing (RNA-Seq) has been performed to determine the variation of transcriptomes and metabolic mechanisms in rice treated with EBR, IPU, or IPU+EBR. Some of the differentially expressed genes (DEGs) were Phase I-III reaction components of plants, such as cytochrome P450 (CYP450), glutathione S-transferase (GST), glycosyltransferases (GTs), and the ATP-binding cassette transporter (ABC transporter). The expression of some signal transduction genes was significantly up-regulated. The relative content of low-toxicity IPU metabolites increased due to the presence of EBR as determined by UPLC/Q-TOF-MS/MS. The IPU metabolic pathways include enzyme-catalyzed demethylation, hydroxylation, hydrolysis, glycosylation, and amino acid conjugation processes. The results suggest that EBR plays a key role in the degradation and detoxification of IPU. This study has provided evidence that BRs regulate the metabolism and detoxification of IPU in rice, and offers a new approach to ensuring cleaner crops by eliminating pesticide residues in the environment.

Postharvest white light combined with different UV-B doses differently promotes anthocyanin accumulation and antioxidant capacity in mango peel

Fruit peel color is an important index of mango fruit quality. Therefore, increasing the anthocyanin accumulation and improving coloration in red mango are crucial for mango industry. The anthocyanin accumulation in mango is light-regulated. However, the effect of white light combined with different doses of UV-B on anthocyanin biosynthesis has not been clarified. Also lacking is a comprehensive analysis of responses of mango fruit peel to UV-B/white light treatments. In this study, green mature ‘Guifei’ mango fruits were subjected to white light combined with low (WL + UV-BL) or high dose UV-B (WL + UV-BH). Anthocyanin concentration, anthocyanin-related gene expression, reactive oxygen species (ROS), antioxidant, and plant hormone concentrations, and antioxidant enzyme activity were measured. The results showed that especially a WL + UV-BH regimen promoted anthocyanin formation in mango peel. Anthocyanin- and light signal-related gene expression, ROS content, antioxidant enzyme activity, antioxidant concentrations, and total antioxidant capacity were also increased by UV-B/white light. Such treatments led to higher concentrations of jasmonic acid and cytokinin, but decreased content of 1-aminocyclopropane-1-carboxylic acid and salicylic acid. Commercially, our findings may contribute to improving the commercial quality of mango. Scientifically, the present data sheds light on the mango fruit peel-specific molecular and physiological response network under UV-B/white light treatments.

Monitoring of molecular responses to tirabrutinib in a cohort of exceptional responders with relapsed/refractory mantle cell lymphoma.

Monitoring of molecular responses to tirabrutinib in a cohort of exceptional responders with relapsed/refractory mantle cell lymphoma.

From the rhizosphere to plant fitness: Implications of microplastics soil pollution

Microplastics (MPs) are a widespread contaminant in the terrestrial environment, with potential impacts on the soil-plant system not yet well understood. This study explores the effects of oxidised low-density polyethylene-MPs (LDPE-MPs) on the rhizosphere ecology and plant fitness of Fragaria x ananassa (Duchesne ex Weston) Duchesne ex Rozier. The rhizospheric microbial community was investigated under the influence of 0,5 % LDPE-MPs by internal transcribed spacer (ITS) and 16 S rRNA metagenomic analysis; photosynthetic parameters, antioxidant enzyme activities, and nutrient accumulation were assessed to evaluate plant physiological and biochemical status. Genes related to jasmonic acid (JA), ethylene biosynthesis, and nitrate signalling pathways were analysed to define the plant molecular response. Our results showed a shift in the rhizosphere microbial community. We identified MPs molecular biomarkers in the contaminated rhizosphere (Fusarium, Thanatephorus and Pseudallescheria) with potential pathogenic functions and two novel molecular biomarkers (Ohtaekwangia and Ascobolus). MPs pollution negatively impacts plant fitness, which showed decreased chlorophyll a and b (40 and 48 %, respectively), a change in nutrient content (fluctuations between 14,42 and 26,7 %) at the leaf level and increased activity of antioxidant enzymes. Gene expression related to JA, ethylene biosynthesis, and nitrogen signalling pathways is enhanced in plants grown in contaminated soil, as well as the root endophytic and epiphytic microorganism interactions. Our results demonstrate that MPs pollution influences the rhizosphere microbial community and functions, and consequently, negatively impacts plant health.

Effects of Exogenous Application of Methyl Jasmonate and Salicylic Acid on the Physiological and Molecular Response of 'Dusa' Avocado to Rosellinia necatrix.

Methyl jasmonate (MeJA) and salicylic acid (SA) are important in mediating plant responses to abiotic and biotic stresses. MeJA and SA can act as elicitors by triggering plant defense responses similar to those induced by pathogens and may even provide long-term protection against them. Thus, exogenous application of MeJA and SA could protect susceptible avocado plants against white root rot (WRR) disease caused by the necrotrophic fungus Rosellinia necatrix, one of the main diseases affecting avocado orchards. This work evaluates the effects of MeJA or SA on the physiological and molecular response of susceptible 'Dusa' avocado rootstock and their ability to provide some protection against WRR. The application of MeJA and SA in avocado increased photoprotective mechanisms (nonphotochemical chlorophyll fluorescence quenching) and upregulated the glutathione S-transferase, suggesting the triggering of mechanisms closely related to oxidative stress relief and reactive oxygen species scavenging. In contrast to SA, MeJA's effects were more pronounced at the morphoanatomical level, including functional traits such as high leaf mass area, high stomatal density, and high root/shoot ratio, closely related to strategies to cope with water scarcity and WRR disease. Moreover, MeJA upregulated a greater number of defense-related genes than SA, including a glu protease inhibitor, a key gene in avocado defense against R. necatrix. The overall effects of MeJA increased 'Dusa' avocado tolerance to R. necatrix by inducing a primed state that delayed WRR disease symptoms. These findings point toward the use of MeJA application as an environmentally friendly strategy to mitigate the impact of this disease on susceptible avocado orchards.