Epidemiology of clinically unsuspected venous thromboembolism in children with cancer: A population-based study from Maritimes, Canada.

Inconsistencies in the definition of clinically unsuspected venous thromboembolism (VTE) in pediatric patients recently led to the recommendation of standardizing this terminology. Clinically unsuspected VTE (cuVTE) is defined as the presence of VTE on diagnostic imaging performed for indications unrelated to VTE in a patient without symptoms or clinical history of VTE. The prevalence of cuVTE in pediatric cancer patients is unclear. Therefore, the main objective of our study was to determine the prevalence of cuVTE in pediatric cancer patients. All patients 0-18 years old, treated at the IWK in Halifax, Nova Scotia, from August 2005 through December 2019 with a known cancer diagnosis and at least one imaging study were eligible (n = 743). All radiology reports available for these patients were reviewed (n = 18,120). The VTE event was labeled a priori as cuVTE event for radiology reports that included descriptive texts indicating a diagnosis of thrombosis including thrombus, central venous catheter-related, thrombosed aneurysm, tumor thrombosis, non-occlusive thrombus, intraluminal filling defect, or small fragment clot for patients without documentation of clinical history and or signs of VTE. A total of 18,120 radiology reports were included in the review. The prevalence of cuVTE was 5.5% (41/743). Echocardiography and computed tomography had the highest rate of cuVTE detection, and the most common terminologies used to diagnose cuVTE were thrombus and non-occlusive thrombus. The diagnosis of cuVTE was not associated with age, sex, and type of cancer. Future efforts should focus on streamlining radiology reports to characterize thrombi. The clinical significance of these cuVTE findings and their application to management, post-thrombotic syndrome, and survival compared to cases with symptomatic VTE and patients without VTE should be further studied.

Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance.

Measurable residual disease (MRD) surveillance in acute myeloid leukemia (AML) may identify patients destined for relapse and thus provide the option of pre-emptive therapy to improve their outcome. Whilst flow cytometric MRD (Flow-MRD) can be applied to high-risk AML/ myelodysplasia patients, its diagnostic performance for detecting impending relapse is unknown. We evaluated this in a cohort comprising 136 true positives (bone marrows preceding relapse by a median of 2.45 months) and 155 true negatives (bone marrows during sustained remission). At an optimal Flow-MRD threshold of 0.040%, clinical sensitivity and specificity for relapse was 74% and 87% respectively (51% and 98% for Flow-MRD ≥ 0.1%) by 'different-from-normal' analysis. Median relapse kinetics were 0.78 log10/month but significantly higher at 0.92 log10/month for FLT3-mutated AML. Computational (unsupervised) Flow-MRD (C-Flow-MRD) generated optimal MRD thresholds of 0.036% and 0.082% with equivalent clinical sensitivity to standard analysis. C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis.

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vß21.3+ activation in multi-inflammatory syndrome in children.

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vß21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vß21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vß21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.

AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier.

Colorimetric sensing of hydrogen peroxide using capped Morus nigra-sawdust deposited zinc oxide nanoparticles via Trigonella foenum extract.

Hydrogen peroxide (H2O2) is one of the main byproducts of most enzymatic reactions, and its detection is very important in disease conditions. Due to its essential role in healthcare, the food industry, and environmental research, accurate H2O2 determination is a prerequisite. In the present work, Morus nigra sawdust deposited zinc oxide (ZnO) nanoparticles (NPs) were synthesized by the use of Trigonella foenum extract via a hydrothermal process. The synthesized platform was characterized by various techniques, including UV-Vis, FTIR, XRD, SEM, EDX, etc. FTIR confirmed the presence of a Zn‒O characteristic peak, and XRD showed the hexagonal phase of ZnO NPs with a 35 nm particle size. The EDX analysis confirmed the presence of Zn and O. SEM images showed that the as-prepared nanoparticles are distributed uniformly on the surface of sawdust. The proposed platform (acetic acid-capped ZnO NPs deposited sawdust) functions as a mimic enzyme for the detection of H2O2 in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) colorimetrically. To get the best results, many key parameters, such as the amount of sawdust-deposited nanoparticles, TMB concentration, pH, and incubation time were optimized. With a linear range of 0.001-0.360 µM and an R2 value of 0.999, the proposed biosensor's 0.81 nM limit of quantification (LOQ) and 0.24 nM limit of detection (LOD) were predicted, respectively. The best response for the proposed biosensor was observed at pH 7, room temperature, and 5 min of incubation time. The acetic acid-capped sawdust deposited ZnO NPs biosensor was also used to detect H2O2 in blood serum samples of diabetic patients and suggest a suitable candidate for in vitro diagnostics and commercial purposes.

Biogenic Salvia species synthesized silver nanoparticles with catalytic, sensing, antimicrobial, and antioxidant properties.

Salvia (Lamiaceae family) is used as a brain tonic to improve cognitive function. The species including S. plebeia and S. moorcroftiana are locally used to cure hepatitis, cough, tumours, hemorrhoids, diarrhoea, common cold, flu, and asthma. To the best of authors' knowledge, no previous study has been conducted on synthesis of S. plebeia and S. moorcroftiana silver nanoparticles (SPAgNPs and SMAgNPs). The study was aimed to synthesize AgNPs from the subject species aqueous and ethanol extracts, and assess catalytic potential in degradation of standard and extracted (from yums, candies, and snacks) dyes, nitrophenols, and antibiotics. The study also aimed at AgNPs as probe in sensing metalloids and heavy metal ions including Pb2+, Cu2+, Fe3+, Ni2+, and Zn2+. From the results, it was found that Salvia aqueous extract afforded stable AgNPs in 1:9 and 1:15 (quantity of aqueous extract and silver nitrate solution concentration) whereas ethanol extract yielded AgNPs in 1:10 (quantity of ethanol extract and silver nitrate solution concentration) reacted in sunlight. The size of SPAgNPs and SMAgNPs determined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were 21.7 nm and 19.9 nm, with spherical, cylindrical, and deep hollow morphology. The synthesized AgNPs demonstrated significant potential as catalyst in dyes; Congo red (85 %), methylene blue (75 %), Rhodamine B (<50 %), nitrophenols; ortho-nitrophenol (95-98 %) and para-nitrophenol (95-98 %), dyes extracted from food samples including yums, candies, and snacks. The antibiotics (amoxicillin, doxycycline, levofloxacin) degraded up to 80 %-95 % degradation. Furthermore, the synthesized AgNPs as probe in sensing of Pb2+, Cu2+, and Fe3+ in Kabul river water, due to agglomeration, caused a significant decrease and bathochromic shift of SPR band (430 nm) when analyzed after 30 min. The Pb2+ ions was comparatively more agglomerated and chelated. Thus, the practical applicability of AgNPs in Pb2+ sensing was significant. Based on the results of this research study, the synthesized AgNPs could provide promising efficiency in wastewater treatment containing organic dyes, antibiotics, and heavy metals.

Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth.

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re-grow remain unknown. Here, we examine the well characterised t(8;21) AML sub-type as a model to address this question. Using four primary AML samples and a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.

Discovering Nature's shield: Metabolomic insights into green zinc oxide nanoparticles Safeguarding Brassica parachinensis L. from cadmium stress.

Heavy metal cadmium (Cd) hinders plants' growth and productivity by causing different morphological and physiological changes. Nanoparticles (NPs) are promising for raising plant yield and reducing Cd toxicity. Nonetheless, the fundamental mechanism of nanoparticle-interfered Cd toxicity in Brassica parachineses L. remains unknown. A novel ZnO nanoparticle (ZnO-NPs) was synthesized using a microalgae strain (Chlorella pyrenoidosa) through a green process and characterized by different standard parameters through TEM, EDX, and XRD. This study examines the effect of different concentrations of ZnO-NPs (50 and 100 mgL-1) in B. parachineses L. under Cd stress through ultra-high-performance liquid chromatography/high-resolution mass spectrometry-based untargeted metabolomics profiling. In the presence of Cd toxicity, foliar spraying with ZnO-NPs raised Cu, Fe, Zn, and Mg levels in the roots and/or leaves, improved seedling development, as demonstrated by increased plant height, root length, and shoot and root fresh weight. Furthermore, the ZnO-NPs significantly enhanced the photosynthetic pigments and changed the antioxidant activities of the Cd-treated plants. Based on a metabolomics analysis, 481 untargeted metabolites were accumulated in leaves under normal and Cd-stressed conditions. These metabolites were highly enriched in producing organic acids, amino acids, glycosides, flavonoids, nucleic acids, and vitamin biosynthesis. Surprisingly, ZnO-NPs restored approximately 60% of Cd stress metabolites to normal leaf levels. Our findings suggest that green synthesized ZnO-NPs can balance ions' absorption, modulate the antioxidant activities, and restore more metabolites associated with plant growth to their normal levels under Cd stress. It can be applied as a plant growth regulator to alleviate heavy metal toxicity and improve crop yield in heavy metal-contaminated regions.

Paracetamol-Mediated Synthesis of Silver Nanoparticles and Their Functionalization with Ionic Liquid for the Colorimetric Biosensing of Ascorbic Acid.

Ascorbic acid is a vital biomolecule for human beings. When the body's level of ascorbic acid is abnormal, it can lead to a number of illnesses. Its appropriate concentration is necessary for the oxidation of prostaglandins and cyclic adenosine monophosphate, the production of dopamine, norepinephrine, epinephrine, and carnitine, and the expansion and durability of the collagen triple helix in humans. In the present work, silver nanoparticle synthesis was performed through a paracetamol-mediated approach. Different characterization techniques, such as X-ray diffractometry (XRD), energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM), were used to confirm the prepared nanoparticles. Subsequently, the prepared Ag NPs functionalized with an ionic liquid were used as a sensing platform for ascorbic acid in blood serum samples. To achieve the best possible results, the proposed biosensor was optimized with different parameters such as TMB concentration, time, amount of capped nanoparticles (NPs), and pH. The proposed biosensor offers a sensitive and straightforward method for ascorbic acid with a linear range from 2 × 10-9 to 3.22 × 10-7 M, an LOD of 1.3 × 10-8 M, an LOQ of 4.3 × 10-8 M, and an R2 of 0.9996, Moreover, applications of the proposed biosensor were successfully used for the detection of ascorbic acid in samples of human plasma, suggesting that Ag NPs with high peroxidase-like activity, high stability, and facile synthesis exhibited promising applications in biomedical fields.

Multifarious Plant Growth-Promoting Rhizobacterium Enterobacter sp. CM94-Mediated Systemic Tolerance and Growth Promotion of Chickpea (Cicer arietinum L.) under Salinity Stress.

BACKGROUND: Chickpea is one of the most important leguminous crops and its productivity is significantly affected by salinity stress. The use of ecofriendly, salt-tolerant, plant growth-promoting rhizobacteria (PGPR) as a bioinoculant can be very effective in mitigating salinity stress in crop plants. In the present study, we explored, characterized, and evaluated a potential PGPR isolate for improving chickpea growth under salt stress. METHODS: A potential PGPR was isolated from rhizospheric soils of chickpea plants grown in the salt-affected area of eastern Uttar Pradesh, India. The isolate was screened for salt tolerance and characterized for its metabolic potential and different plant growth-promoting attributes. Further, the potential of the isolate to promote chickpea growth under different salt concentrations was determined by a greenhouse experiment. RESULTS: A rhizobacteria isolate, CM94, which could tolerate a NaCl concentration of up to 8% was selected for this study. Based on the BIOLOG carbon source utilization, isolate CM94 was metabolically versatile and able to produce multiple plant growth-promoting attributes, such as indole acetic acid, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, siderophore, hydrogen cyanide (HCN), and ammonia as well as solubilized phosphate. A polyphasic approach involving the analysis of fatty acid methyl ester (FAME) and 16S rRNA gene sequencing confirmed the identity of the isolate as Enterobacter sp. The results of greenhouse experiments revealed that isolate CM94 inoculation significantly enhanced the shoot length, root length, and fresh and dry weight of chickpea plants, under variable salinity stress. In addition, inoculation improved the chlorophyll, proline, sugar, and protein content in the tissues of the plant, while lowering lipid peroxidation. Furthermore, isolate CM94 reduced oxidative stress by enhancing the enzymatic activities of superoxide dismutase, catalase, and peroxidase compared to in the respective uninoculated plants. CONCLUSIONS: Overall, the results suggested that using Enterobacter sp. CM94 could significantly mitigate salinity stress and enhance chickpea growth under saline conditions. Such studies will be helpful in identifying efficient microorganisms to alleviate salinity stress, which in turn will help, to devise ecofriendly microbial technologies.

Feasibility of mass cytometry proteomic characterisation of circulating tumour cells in head and neck squamous cell carcinoma for deep phenotyping.

BACKGROUND: Circulating tumour cells (CTCs) are a potential cancer biomarker, but current methods of CTC analysis at single-cell resolution are limited. Here, we describe high-dimensional single-cell mass cytometry proteomic analysis of CTCs in HNSCC. METHODS: Parsortix microfluidic-enriched CTCs from 14 treatment-naïve HNSCC patients were analysed by mass cytometry analysis using 41 antibodies. Immune cell lineage, epithelial-mesenchymal transition (EMT), stemness, proliferation and immune checkpoint expression was assessed alongside phosphorylation status of multiple signalling proteins. Patient-matched tumour gene expression and CTC EMT profiles were compared. Standard bulk CTC RNAseq was performed as a baseline comparator to assess mass cytometry data. RESULTS: CTCs were detected in 13/14 patients with CTC counts of 2-24 CTCs/ml blood. Unsupervised clustering separated CTCs into epithelial, early EMT and advanced EMT groups that differed in signalling pathway activation state. Patient-specific CTC cluster patterns separated into immune checkpoint low and high groups. Patient tumour and CTC EMT profiles differed. Mass cytometry outperformed bulk RNAseq to detect CTCs and characterise cell phenotype. DISCUSSION: We demonstrate mass cytometry allows high-plex proteomic characterisation of CTCs at single-cell resolution and identify common CTC sub-groups with potential for novel biomarker development and immune checkpoint inhibitor treatment stratification.

Deep immune B and plasma cell repertoire in non-small cell lung cancer.

Introduction: B cells, which have long been thought to be minor players in the development of anti-tumor responses, have been implicated as key players in lung cancer pathogenesis and response to checkpoint blockade in patients with lung cancer. Enrichment of late-stage plasma and memory cells in the tumor microenvironment has been shown in lung cancer, with the plasma cell repertoire existing on a functional spectrum with suppressive phenotypes correlating with outcome. B cell dynamics may be influenced by the inflammatory microenvironment observed in smokers and between LUAD and LUSC. Methods: Here, we show through high-dimensional deep phenotyping using mass cytometry (CyTOF), next generation RNA sequencing and multispectral immunofluorescence imaging (VECTRA Polaris) that key differences exist in the B cell repertoire between tumor and circulation in paired specimens from lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results: In addition to the current literature, this study provides insight into the in-depth description of the B cell contexture in Non-Small Cell Lung Cancer (NSCLC) with reference to broad clinico-pathological parameters based on our analysis of 56 patients. Our findings reinforce the phenomenon of B-cell trafficking from distant circulatory compartments into the tumour microenvironment (TME). The circulatory repertoire shows a predilection toward plasma and memory phenotypes in LUAD however no major differences exist between LUAD and LUSC at the level of the TME. B cell repertoire, amongst other factors, may be influenced by the inflammatory burden in the TME and circulation, that is, smokers and non-smokers. We have further clearly demonstrated that the plasma cell repertoire exists on a functional spectrum in lung cancer, and that the suppressive regulatory arm of this axis may play a significant role in determining postoperative outcomes as well as following checkpoint blockade. This will require further long-term functional correlation. Conclusion: B and Plasma cell repertoire is very diverse and heterogeneous across different tissue compartments in lung cancer. Smoking status associates with key differences in the immune milieu and the consequent inflammatory microenvironment is likely responsible for the functional and phenotypic spectrum we have seen in the plasma cell and B cell repertoire in this condition.

Posttransplant MRD and T-cell chimerism status predict outcomes in patients who received allografts for AML/MDS.

Allogeneic stem-cell transplant allows for the delivery of curative graft-versus-leukemia (GVL) in patients with acute myeloid leukemia/myelodysplasia (AML/MDS). Surveillance of T-cell chimerism, measurable residual disease (MRD) and blast HLA-DR expression may inform whether GVL effectiveness is reduced. We report here the prognostic impact of these biomarkers in patients allografted for AML/MDS. One hundred eighty-seven patients from FIGARO, a randomized trial of reduced-intensity conditioning regimens in AML/MDS, were alive and relapse-free at the first MRD time-point and provided monitoring samples for flow cytometric MRD and T-cell chimerism, requested to month+12. Twenty-nine (15.5%) patients had at least 1 MRD-positive result posttransplant. MRD-positivity was associated with reduced overall survival (OS) (hazard ratio [HR], 2.18; P = .0028) as a time-varying Cox variable and remained significant irrespective of pretransplant MRD status in multivariate analyses (P < .001). Ninety-four patients had sequential MRD with T-cell chimerism results at months+3/+6. Patients with full donor T-cell chimerism (FDTC) had an improved OS as compared with patients with mixed donor T-cell chimerism (MDTC) (adjusted HR=0.4; P = .0019). In patients with MDTC (month+3 or +6), MRD-positivity was associated with a decreased 2-year OS (34.3%) vs MRD-negativity (71.4%) (P = .001). In contrast, in the group with FDTC, MRD was infrequent and did not affect the outcome. Among patients with posttransplant MRD-positivity, decreased HLA-DR expression on blasts significantly reduced OS, supporting this as a mechanism for GVL escape. In conclusion, posttransplant MRD is an important predictor of the outcome in patients allografted for AML/MDS and is most informative when combined with T-cell chimerism results, underlining the importance of a GVL effect in AML/MDS.

Integrated Application of Salicylic Acid and PGPRs to Control Fusarium Wilt of Chickpea.

BACKGROUND: Fusarium wilt and Ascochyta blight are the most important diseases of chickpea. The current study was designed to investigate the individual and combined effect of salicylic acid (SA) with Pseudomonas stutzeri and Pseudomonas putida to suppress Fusarium wilt and promote growth of chickpea varieties: Thal-2006 and Punjab-2008. METHODS: At the time of sowing, inoculum of Fusarium oxysporum was applied to the soil and the incidence of Fusarium wilt was recorded after 60 days. The seeds were inoculated with Pseudomonas stutzeri and Pseudomonas putida prior to sowing. Chickpea plants were treated with salicylic acid at seedling stage. RESULTS: The combination of P. stutzeri and SA significantly increased root length (166% and 145%), shoot height (50% and 47%) and shoot biomass (300% and 233%) in cv. Thal-2006 and cv. Punjab-2008, respectively, in infected plants. Similarly, the combined treatment of P. putida + SA, also enhanced the plant growth parameters of chickpea varieties. Maximum reduction in disease severity was observed in both P. stutzeri + SA (90% and 84%) and P. putida + SA (79% and 77%) treatments in cv. Thal-2006 and Punjab-2008, respectively. Both P. putida + SA and P. stutzeri + SA treatments resulted in increased leaf relative water and total protein content, peroxidase, superoxide dismutase, phenylalanine ammonia-lyase and polyphenol oxidase activities in both resistant (cv. Thal-2006) and susceptible (cv. Punjab-2008) cultivars. Both treatments also significantly reduced malondialdehyde (MDA) and proline content in cv. Thal-2006 and Punjab-2008. Cultivar Thal-2006 was more effective than cv. Punjab-2008. CONCLUSIONS: The results suggested that, in combination, salicylic acid and P. stutzeri may play an important role in controlling Fusarium wilt diseases by inducing systemic resistance in chickpea.

Application of silver nanoparticles synthesized through varying biogenic and chemical methods for wastewater treatment and health aspects.

Nanotechnology uses biological and non-biological materials to create new systems at the nanoscale level. In recent years, the use of silver nanomaterials has attracted worldwide attention thanks to their wide range of applications as catalysts in several environmental processes including the degradation of organic pollutants and medicinal biotechnology. This study reports the synthesis of silver nanoparticles (AgNPs) through different methods including the biogenic methods based on leaf extract of Conocarpus erectus and a bacterial strain Pseudomonas sp. as well as chemically based abiotic method and comparison of their dye degradation potential. The synthesis of AgNPs in all samples was confirmed by UV-visible spectroscopy peaks at 418-420 nm. Using scanning electrom microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray differaction (XRD), and X-ray photoelectron spectroscopy (XPS), the biologically synthesized AgNPs were characterized as spherical shape of material with capping proteins that were involved in the stabilization of nanoparticles (NPs). The biologically synthesized AgNPs showed higher degradation (< 90%) of dyes as compared to chemically synthesized NPs. A prominent reduction of total dissolved solids (TDS), electrical conductivity (EC), pH, and chemical oxygen demand (COD) in textile wastewater spiked with reactive black 5 and reactive red 120 was observed by biologically synthesized AgNPs. AgNPs synthesized by Conocarpus erectus and Pseudomonas sp. also showed better characteristic anticancer and antidiabetic activities as compared to chemically synthesized ones. The results of this study suggested that C. erectus and Pseudomonas sp. based AgNPs can be exploited as an eco-friendly and cost-efficient materials to treat the wastewater and potential other polluted environments as well as to serve the medicinal field.

Impression of foliar-applied folic acid on coriander (Coriandrum sativum L.) to regulate aerial growth, biochemical activity, and essential oil profiling under drought stress.

Drought is one of the major environmental limitations in the crop production sector that has a great impact on food security worldwide. Coriander (Coriandrum sativum L.) is an herbaceous angiosperm of culinary significance and highly susceptible to rootzone dryness. Elucidating the drought-induced physio-chemical changes and the foliar-applied folic acid (FA; vitamin B9)-mediated stress tolerance mechanism of coriander has been found as a research hotspot under the progressing water scarcity challenges for agriculture. The significance of folic acid in ameliorating biochemical activities for the improved vegetative growth and performance of coriander under the mild stress (MS75), severe stress (SS50), and unstressed (US100) conditions was examined in this study during two consecutive seasons. The results revealed that the plants treated with 50 mM FA showed the highest plant fresh biomass, leaf fresh biomass, and shoot fresh biomass from bolting stage to seed filling stage under mild drought stress. In addition, total soluble sugars, total flavonoids content, and chlorophyll content showed significant results by the foliar application of FA, while total phenolic content showed non-significant results under MS75 and SS50. It was found that 50 mM of FA upregulated the activity of catalase, superoxide dismutase, and ascorbate peroxidase enzymes in MS75 and SS50 plants compared with untreated FA plants. Thus, FA treatment improved the overall biological yield and economic yield regardless of water deficit conditions. FA-accompanied plants showed a decline in drought susceptibility index, while it improved the drought tolerance efficiency, indicating this variety to become stress tolerant. The optimum harvest index, essential oil (EO) percentage, and oil yield were found in MS75 followed by SS50 in FA-supplemented plants. The gas chromatography-mass spectrometry analysis revealed a higher abundance of linalool as the major chemical constituent of EO, followed by α-terpeniol, terpinene, and p-Cymene in FA-treated SS50 plants. FA can be chosen as a shotgun tactic to improve drought tolerance in coriander by delimiting the drastic changes due to drought stress.

Indole pyruvate decarboxylase gene regulates the auxin synthesis pathway in rice by interacting with the indole-3-acetic acid-amido synthetase gene, promoting root hair development under cadmium stress.

This research focused on cadmium (Cd), which negatively affects plant growth and auxin hemostasis. In plants, many processes are indirectly controlled through the expression of certain genes due to the secretion of bacterial auxin, as indole-3-acetic acid (IAA) acts as a reciprocal signaling molecule in plant-microbe interaction. The aim of current studies was to investigate responsible genes in rice for plant-microbe interaction and lateral root development due to the involvement of several metabolic pathways. Studies revealed that GH3-2 interacts with endogenous IAA in a homeostasis manner without directly providing IAA. In rice, indole-3-pyruvate decarboxylase (IPDC) transgenic lines showed a 40% increase in lateral roots. Auxin levels and YUCCA (auxin biosynthesis gene) expression were monitored in osaux1 mutant lines inoculated with Bacillus cereus exposed to Cd. The results showed an increase in root hairs (RHs) and lateral root density, changes in auxin levels, and expression of the YUCCA gene. B. cereus normalizes the oxidative stress caused by Cd due to the accumulation of O 2 - and H2O2 in osaux1 mutant lines. Furthermore, the inoculation of B. cereus increases DR5:GUS expression, indicating that bacterial species have a positive role in auxin regulation. Thus, the current study suggests that B. cereus and IPDC transgenic lines increase the RH development in rice by interacting with IAA synthetase genes in the host plant, alleviating Cd toxicity and enhancing plant defense mechanisms.

Development of a Nonenzymatic Colorimetric Sensor for the Detection of Uric Acid Based on Ionic Liquid-Mediated Nickel Nanostructures.

Uric acid (UA) is a metabolic byproduct of purine nucleotides and is excreted as a urine component. Abnormalities in UA metabolism cause localized inflammation due to crystal deposition and can lead to various diseases. In the current study, we successfully fabricated a biosensor based on 1-H-3-methylimidazolium acetate (ionic liquid, IL)-capped nickel nanoparticles (NiNPs) for the detection of uric acid in test samples. The structures of IL-capped NiNPs and their precursors were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The IL-capped NiNPs possessed intrinsic peroxidase-like properties and displayed selective UA quenching after interacting with 3,3',5,5'-tetramethylbenzidine (TMB) solution. Different parameters such as pH, time, IL, TMB, and UA concentration were optimized to obtain the best results for the proposed sensor. The UA biosensor shows good responses in the linear range from 1 × 10-8 to 2.40 × 10-6 M, with a lower limit of detection of 1.30 × 10-7 M, a limit of quantification of 4.3 × 10-7 M, and an R 2 value of 0.9994. For the colorimetric detection of UA, the proposed sensor gave a short time response of 4 min at room temperature and pH 7.5. The proposed sensing probe detects UA in real serum samples and could be used as a selective sensor for UA in the real sample detection.

B-Cell-Based Immunotherapy: A Promising New Alternative.

The field of immunotherapy has undergone radical conceptual changes over the last decade. There are various examples of immunotherapy, including the use of monoclonal antibodies, cancer vaccines, tumor-infecting viruses, cytokines, adjuvants, and autologous T cells carrying chimeric antigen receptors (CARs) that can bind cancer-specific antigens known as adoptive immunotherapy. While a lot has been achieved in the field of T-cell immunotherapy, only a fraction of patients (20%) see lasting benefits from this mode of treatment, which is why there is a critical need to turn our attention to other immune cells. B cells have been shown to play both anti- and pro-tumorigenic roles in tumor tissue. In this review, we shed light on the dual nature of B cells in the tumor microenvironment. Furthermore, we discussed the different factors affecting the biology and function of B cells in tumors. In the third section, we described B-cell-based immunotherapies and their clinical applications and challenges. These current studies provide a springboard for carrying out future mechanistic studies to help us unleash the full potential of B cells in immunotherapy.

Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade.

Checkpoint blockade with Pembrolizumab, has demonstrated durable clinical responses in advanced non-small cell lung cancer, however, treatment is offset by the development of high-grade immune related adverse events (irAEs) in some patients. Here, we show that in these patients a deficient Breg checkpoint fails to limit self-reactive T cell enhanced activity and auto-antibody formation enabled by PD-1/PD-L1 blockade, leading to severe auto-inflammatory sequelae. Principally a failure of IL-10 producing regulatory B cells as demonstrated through functional ex vivo assays and deep phenotyping mass cytometric analysis, is a major and significant finding in patients who develop high-grade irAEs when undergoing treatment with anti-PD1/PD-L1 checkpoint blockade. There is currently a lack of biomarkers to identify a priori those patients at greatest risk of developing severe auto-inflammatory syndrome. Pre-therapy B cell profiling could provide an important tool to identify lung cancer patients at high risk of developing severe irAEs on checkpoint blockade.