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UV-A, an important part of sunlight radiation, is typically absent in experiments on plant-endophyte interactions. We examined the impact of UV-A in the 350–400 nm range (UV-A1 waveband) on the plant interactions with fungal endophytes belonging to different taxonomic groups: Paraphoma chrysanthemicola , Phomopsis columnaris , Diaporthe eres , Mucor sp., and yeast Sporobolomyces ruberrimus . Physiologically relevant levels of UV-A did not substantially affect the colonisation of shoots and roots by endophytes. UV-A upregulated the expression of genes involved in the establishment of symbiosis. Specifically, the expression of PDF1.2 was affected by P. chrysanthemicola and S. ruberrimus only under UV-A conditions. Additionally, UV-A exposure upregulated the mRNA levels of ICS1 and PAL1 , genes important for plant responses to stress factors. Inoculation with P. chrysanthemicola and S. ruberrimus led to increased expression of the ICS1 gene. We did not observe significant interactions between the effects of UV-A and the presence of endophytes on other examined plant traits, including plant fresh weight, root system architecture, and expression of plant photoreceptor genes. For these physiological parameters, the effects of the presence of endophytes did not depend on UV-A supplementation. Our findings indicate that while UV-A does not substantially influence plant colonisation by the endophytes, it does trigger the upregulation of plant defence genes and affects the shoot growth of Arabidopsis .

Intensive crop production leads to the disruption of the symbiosis between plants and their associated microorganisms, resulting in suboptimal plant productivity and lower yield quality. Therefore, it is necessary to improve existing methods and explore modern, environmentally friendly approaches to crop production. One of these methods is biotization, which involves the inoculation of plants with appropriately selected symbiotic microorganisms which play a beneficial role in plant adaptation to the environment. In this study, we tested the possibility of using a multi-microorganismal inoculum composed of arbuscular mycorrhizal fungi (AMF) and AMF spore-associated bacteria for biotization of the red raspberry. Bacteria were isolated from the spores of AMF, and their plant growth-promoting properties were tested. AMF inocula were supplemented with selected bacterial strains to investigate their effect on the growth and vitality of the raspberry. The investigations were carried out in the laboratory and on a semi-industrial scale in a polytunnel where commercial production of seedlings is carried out. In the semi-industrial experiment, we tested the growth parameters of plants and physiological response of the plant to temporary water shortage. We isolated over fifty strains of bacteria associated with spores of AMF. Only part of them showed plant growth-promoting properties, and six of these (belonging to the Paenibacillus genus) were used for the inoculum. AMF inoculation and co-inoculation of AMF and bacteria isolated from AMF spores improved plant growth and vitality in both experimental setups. Plant dry weight was improved by 70%, and selected chlorophyll fluorescence parameters (the contribution of light to primary photochemistry and fraction of reaction centre chlorophyll per chlorophyll of the antennae) were increased. The inoculum improved carbon assimilation, photosynthetic rate, stomatal conductance and transpiration after temporary water shortage. Raspberry biotization with AMF and bacteria associated with spores has potential applications in horticulture where ecological methods based on plant microorganism interaction are in demand.

Root transcriptomic profile was comparatively studied in a serpentine (TM) and a non-metallicolous (NTM) population of Noccaea goesingensis in order to investigate possible features of Ni hyperaccumulation. Both populations were characterised by contrasting Ni tolerance and accumulation capacity. The growth of the TM population was unaffected by metal excess, while the shoot biomass production in the NTM population was significantly lower in the presence of Ni in the culture medium. Nickel concentration was nearly six- and two-fold higher in the shoots than in the roots of the TM and NTM population, respectively. The comparison of root transcriptomes using the RNA-seq method indicated distinct responses to Ni treatment between tested ecotypes. Among differentially expressed genes, the expression of IRT1 and IRT2, encoding metal transporters, was upregulated in the TM population and downregulated/unchanged in the NTM ecotype. Furthermore, differences were observed among ethylene metabolism and response related genes. In the TM population, the expression of genes including ACS7, ACO5, ERF104 and ERF105 was upregulated, while in the NTM population, expression of these genes remained unchanged, thus suggesting a possible regulatory role of this hormone in Ni hyperaccumulation. The present results could serve as a starting point for further studies concerning the plant mechanisms responsible for Ni tolerance and accumulation.

Ecological methods are becoming increasingly popular. One of these methods is plant biotization. In our paper, we focus on selection of Vaccinium corymbosum hairy root-inhabiting fungi for plant growth promotion in a single microorganism inoculation setup and then composed a multiorganismal inoculum enriched with a representative of another group of fungi, leaf endophytes. The hairy roots of V. corymbosum hosted 13 fungal taxa. In single inoculation of the plant with fungal strains, the most beneficial for plant growth were Oidiodendron maius and Phialocephala fortinii . Additional inoculation of the plants with three root symbiotic fungi ( O. maius , Hymenoscyphus sp. and P. fortinii ) and with the endophytic fungus Xylaria sp. increased plant height in laboratory experiments. On a semi-industrial scale, inoculation improved plant biomass and vitality. Therefore, the amendment of root-associated fungal communities with a mixture of ericoid mycorrhizal and endophytic fungi may represent an alternative to conventional fertilization and pesticide application in large-scale blueberry production. Key points • O. maius and P. fortinii significantly stimulated V. corymbosum growth in a single inoculation. • Multimicroorganismal inoculum increased plant biomass and vitality. • Blueberry biotization with ericoid and endophytic fungi is recommended. Graphical abstract

Plant-associated microbial communities play a vital role in host adaptation to environmental stress, yet their contributions to plant nickel (Ni) tolerance strategies remain unclear. It is not understood whether the same microbial community elicits similar responses across different plant species or regulates stress adaptation in a host-specific manner. Although microorganisms influence plant responses to metal toxicity by altering metal bioavailability in the rhizosphere, their potential to optimize plant metal uptake is less explored. In this study, we evaluated whether synthetic microbial communities enhance Ni uptake in two species with contrasting metal strategies: the hyperaccumulator Odontarrhena chalcidica and the Ni-excluding Arabidopsis arenosa. We hypothesized that soil microorganisms support plant metal adaptation by improving physiological function rather than altering soil metal availability. Our results show that O. chalcidica reached its full hyperaccumulating potential only when co-cultivated with a soil-derived microbial community, regardless of the microorganisms’ ability to mobilize Ni or promote plant growth. Microorganisms that enhanced Ni uptake had no effect on soil Ni availability. Microbial community analysis revealed species-specific microbiota assembly, with O. chalcidica being more responsive yet more selective. Serpentine-soil microbiota enhanced Ni uptake in O. chalcidica by upregulating iron-transporter genes, confirming reliance on Fe-transport pathways for Ni acquisition. In contrast, the same inoculum induced Zn-transporters and NRT2.1/NRT2.2 in A. arenosa, reflecting strategy of cation partitioning and nutrient-transport fine-tuning under Ni stress. These findings refine criteria for selecting microorganisms in phytoremediation and highlight that the functional impact of plant-associated microorganisms on metal handling outweigh their effects on metal solubility in soil.

CD20 located predominantly on the B cells plays a crucial role in their development, differentiation, and activation, and serves as a key therapeutic target for the treatment of B-cell malignancies. The breakthrough of monoclonal antibodies directed against CD20, notably exemplified by rituximab, revolutionized the prognosis of B-cell malignancies. Rituximab, approved across various hematological malignancies, marked a paradigm shift in cancer treatment. In the current landscape, immunotherapies targeting CD20 continue to evolve rapidly. Beyond traditional mAbs, advancements include antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor-modified (CAR) T cells. ADCs combine the precision of antibodies with the cytotoxic potential of drugs, presenting a promising avenue for enhanced therapeutic efficacy. BsAbs, particularly CD20xCD3 constructs, redirect cytotoxic T cells to eliminate cancer cells, thereby enhancing both precision and potency in their therapeutic action. CAR-T cells stand as a promising strategy for combatting hematological malignancies, representing one of the truly personalized therapeutic interventions. Many new therapies are currently being evaluated in clinical trials. This review serves as a comprehensive summary of CD20-targeted therapies, highlighting the progress and challenges that persist. Despite significant advancements, adverse events associated with these therapies and the development of resistance remain critical issues. Understanding and mitigating these challenges is paramount for the continued success of CD20-targeted immunotherapies.

The prognosis for B-cell precursor acute lymphoblastic leukemia patients with Mixed-Lineage Leukemia ( MLL ) gene rearrangements (MLLr BCP-ALL) is still extremely poor. Inhibition of anti-apoptotic protein BCL-2 with venetoclax emerged as a promising strategy for this subtype of BCP-ALL, however, lack of sufficient responses in preclinical models and the possibility of developing resistance exclude using venetoclax as monotherapy. Herein, we aimed to uncover potential mechanisms responsible for limited venetoclax activity in MLLr BCP-ALL and to identify drugs that could be used in combination therapy. Using RNA-seq, we observed that long-term exposure to venetoclax in vivo in a patient-derived xenograft model leads to downregulation of several tumor protein 53 ( TP53 )-related genes. Interestingly, auranofin, a thioredoxin reductase inhibitor, sensitized MLLr BCP-ALL to venetoclax in various in vitro and in vivo models, independently of the p53 pathway functionality. Synergistic activity of these drugs resulted from auranofin-mediated upregulation of NOXA pro-apoptotic protein and potent induction of apoptotic cell death. More specifically, we observed that auranofin orchestrates upregulation of the NOXA-encoding gene Phorbol-12-Myristate-13-Acetate-Induced Protein 1 ( PMAIP1 ) associated with chromatin remodeling and increased transcriptional accessibility. Altogether, these results present an efficacious drug combination that could be considered for the treatment of MLLr BCP-ALL patients, including those with TP53 mutations.

The monitoring of children with cerebral palsy (CP) should include a precise assessment of the nutritional status to identify children and adolescents at risk of nutrition disorders. Available studies assessing the nutritional status of children with CP mainly focus on the relationship between body composition and the coexistence of motor dysfunctions, frequently overlooking the role of muscle tone. Therefore, the aim of this study was to assess the relationship between body composition and muscle tone in children with CP. In a case-control study (n = 118; mean age 11 y; SD = 3.8), the children with CP presented various stages of functional capacities, corresponding to all the levels in gross motor function classification system (GMFSC), and muscle tone described by all the grades in Ashworth scale. The control group consisted of healthy children and adolescents, strictly matched for gender and age in a 1:1 case-control manner. The children with CP were found with significantly lower mean values of fat-free mass (FFM kg = 29.2 vs. 34.5, p < 0.001), muscle mass (MM kg = 18.6 vs. 22.6, p < 0.001), body cell mass (BCM kg = 15.1 vs. 18.3, p < 0.001), and total body water (TBW L = 23.0 vs. 26.7, p < 0.001). The same differences in body composition were identified with respect to gender (p < 0.01 respectively). Moreover, children with higher muscle tone (higher score in Ashworth scale) were found with significantly lower values of fat mass (FM), FFM, MM, BCM, and TBW (p < 0.05). The findings showed lower parameters of body composition in the children with CP compared to the healthy children, and a decrease in the parameters coinciding with higher muscle tone in the study group. This observation suggests that it is necessary to measure muscle tone while assessing nutritional status of children with CP.

B-cell malignancies are a heterogeneous group of hematological neoplasms derived from cells at different stages of B-cell development. Recent studies revealed that dysregulated redox metabolism is one of the factors contributing to the pathogenesis and progression of B-cell malignancies. Elevated levels of oxidative stress markers usually correlate with the advanced stage of various B-cell malignancies. In the complex tumor microenvironment, reactive oxygen species affect not only malignant cells but also bystander cells, including immune cells. Importantly, malignant cells, due to genetic dysregulation, are able to adapt to the increased demands for energy and reducing equivalents via metabolic reprogramming and upregulation of antioxidants. The immune cells, however, are more sensitive to oxidative imbalance. This may cause their dysfunction, leading to immune evasion and tumor progression. On the other hand, the already imbalanced redox homeostasis renders malignant B-cells particularly sensitive to further elevation of reactive oxygen species. Indeed, targeting antioxidant systems has already presented anti-leukemic efficacy in preclinical models. Moreover, the prooxidant treatment that triggers immunogenic cell death has been utilized to generate autologous anti-leukemic vaccines. In this article, we review novel research on the dual role of the reactive oxygen species in B-cell malignancies. We highlight the mechanisms of maintaining redox homeostasis by malignant B-cells along with the antioxidant shield provided by the microenvironment. We summarize current findings regarding therapeutic targeting of redox metabolism in B-cell malignancies. We also discuss how the oxidative stress affects antitumor immune response and how excessive reactive oxygens species influence anticancer prooxidant treatments and immunotherapies.

This study aimed to perform linguistic and cross-cultural adaptation to establish a Polish version of the Lower Limb Functional Index (LLFI) as well as an evaluation of the psychometric properties. This was a two-stage, cross-sectional study. The first stage—linguistic and cultural adaptation, complied with the International Society for Pharmacoeconomics and Outcomes Research guidelines to produce the Lower Limb Functional Index, Polish version (LLFI-PL). The subjects were recruited to the second stage of the study from a sample of convenience (n = 125, age x- = 52.86 ± 19.53 years, 56% female, symptoms duration x- = 17.69 ± 18.39 weeks). Baseline reliability was performed on the LLFI-PL with retest period at 3–7 days. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC), EuroQol Health Questionnaire 5-Dimensions 5-Level (EQ-5D-5L), and an 11-point Pain Numerical Rating Scale (P-NRS) were completed to assess the validity of the LLFI-PL. Statistical analysis showed high internal consistency (α = 0.94), and excellent test–retest reliability (ICC2.1 = 0.96). The measurement error was SEM = 1.69% with MDC90 = 3.93%. Construct validity demonstrated strong correlations between the LLFI-PL and WOMAC (r = 0.81) and moderate correlations with the EQ-5D-5L (r = −0.63) and P-NRS (r = −0.39). Exploratory factor analysis confirmed a single-factor structure. The LLFI-PL is a psychometrically sound questionnaire for Polish-speaking patients with lower limb musculoskeletal conditions. The results support findings from the previous original English, Spanish, and Turkish versions.