The plant endomicrobiome: Structure and strategies to produce stress resilient future crop.

Plants have a microbiome, a diverse community of microorganisms, including bacteria, fungi, and viruses, living inside and on their tissues. Versatile endophytic microorganisms inhabited in every plant part without causing disease and develop endophytic microbiome or endo-microbiome. Plant endo-microbiome are drawn by the nutrient rich micro-environment, and in turn some microbes mutualistically endorse and protect plant from adverse environmental stresses. Plant endo-microbiome interact within well-designed host equilibrium containing xylem, phloem, nutrients, phytohormones, metabolites and shift according to environmental and nutritional change. Plant endo-microbiome regulate and respond to environmental variations, pathogens, herbivores by producing stress regulators, organic acids, secondary metabolites, stress hormones as well as unknown substances and signalling molecules. Endomicrobiome efficiently synthesizes multiple bioactive compounds, stress phytohormones with high competence. The technological innovation as next generation genomics biology and high-throughput multiomics techniques stepping stones on the illumination of critical endo-microbiome communities and functional characterization that aid in improving plant physiology, biochemistry and immunity interplay for best crop productivity. This review article contains deeper insight in endomicrobiome related research work in last years, recruitment, niche development, nutrient dynamics, stress removal mechanisms, bioactive services in plant health development, community architecture and communication, and immunity interplay in producing stress resilient future crop.

Synergistic effect between ZnCo2O4 and Co3O4 induces superior electrochemical performance as anodes for lithium-ion batteries.

The current work describes a facile synthesis of spinel-type ZnCo2O4 along with an additional phase, Co3O4, by simply maintaining a non-stoichiometric ratio of Zn and Co precursors. Pure ZnCo2O4 and Co3O4 were also synthesized using the same method to compare results. The obtained morphologies of samples show that small-sized nanoparticles are interconnected and form a porous nanosheet-like structure. When used as anode materials for Li-ion batteries, the ZnCo2O4/Co3O4 nanocomposite electrode exhibits a highly stable charge capacity of 1146.2 mA h g-1 at 0.5C after 350 cycles, which is superior to those of other two pure electrodes, which can be attributed to its optimum porosity, synergistic effect of ZnCo2O4 and Co3O4, increased active sites for Li+ ion diffusion, and higher electrical conductivity. Although the pure Co3O4 electrode displayed a much higher rate capability than the ZnCo2O4/Co3O4 nanocomposite electrode at all investigated current rates, the Co3O4 morphology apparently could not withstand long-term cycling, and the electrode became pulverized due to the repeated volume expansion/contraction, resulting in a rapid decrease in the capacity.

Testing prescribed burning to shift an agronomic grass community to a diverse native plant community.

Prescribed burning can be an effective land management tool. Here, we study changes in plant diversity and composition following experimental fire disturbance in microcosm units extracted from a twenty-five-year-old historically reclaimed grassland located at Highland Valley Copper mine in British Columbia (B.C.), Canada. Experimental microcosm units were dominated by agronomic grass species Elymus lanceolatus, Thinopyrum intermedium and Bromus inermis. The disturbance treatment was fire intensity, represented by three levels (light, moderate, and heavy), replicated six times per treatment. Fire intensity was controlled by modifying the weight of dried litter applied to each microcosm unit (50 g,150 g, 200g), along with the time each grass turf was burned (10 s, 15 s, 20 s). One day after the fire treatment was applied, microcosm units were seeded with a native species mix consisting of six grassland species common to southern B.C. to examine effectiveness of plant establishment postburn. Disturbance treatments resulted in higher overall alpha diversity, richness, evenness, and beta diversity. Plant community changes included colonization of seeded native forbs, grasses, and legumes in response to disturbance. Aboveground net primary productivity (ANPP) was net neutral within the light and moderate burning disturbance treatments but resulted in increased ANPP with heavy disturbance. Litter mass reduced plant diversity and ANPP, indicating that litter was a major factor in plant community dynamics. These results suggest disturbance by burning leads to short term positive plant community response towards increasing diversity of semi-arid grasslands, and aids in shifting plant communities to higher diversity composed of an increase in native plant species. Our results also suggest that without active management the gains observed in native species establishment might quickly be out shadowed and restricted by the previously dominant agronomic plant community.

Physical characterization and bioavailability assessment of 5-fluorouracil-based nanostructured lipid carrier (NLC): In vitro drug release, Hemolysis, and permeability modulation.

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitro and in vivo performance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25 nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4 h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30 days. Additionally, an in vitro hemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10-5 cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed through in vivo pharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.

Chitosan-assisted self-assembly of flower-shaped ε-Fe2O3 nanoparticles on screen-printed carbon electrode for Impedimetric detection of Cd2+, Pb2+, and Hg2+ heavy metal ions in various water samples.

This study focuses on the fabrication of a novel sensing platform on a screen-printed carbon electrode, modified by a combination of hydrothermally synthesized iron dioxide (ε-Fe2O3) nanoparticles and Chitosan (CS) biopolymer. This unique organic-inorganic hybrid material was developed for Electrochemical Impedance Spectroscopy (EIS) sensing, specifically targeting heavy metal ions that include Hg2+, Cd2+, as well as Pb2+. The investigation encompassed a comprehensive analysis of various aspects of the prepared Fe2O3 and CS/ε-Fe2O3 nanocomposites, including phase identification, determination of crystallite size, assessment of surface morphology, etc. CS/ε-Fe2O3 was drop-casted and deposited on the Screen-Printed Electrode (SPE). The resulting sensor exhibited excellent performance in the precise and selective quantification of Hg2+, Cd2+, and Pb2+ ions, with minimal interference from other substances. The fabricated sensor exhibits excellent performance as the detection range for Hg2+, Cd2+, and Pb2+ ions linearity is 2-20 µM, sensitivity, and LOD are 243 Ω/ µM cm2 and 0.191 µM, 191 Ω/µM cm2, and 0.167 µM, 879 Ω/ µM cm2, and 0.177 µM respectively. The stability of the CS/ε-Fe2O3/SPE electrode is demonstrated by checking its conductivity for up to 60 days for Hg2+, Cd2+, and Pb2+ ions. The reusability of the fabricated electrode is 14 scans, 13 scans, and 12 scans for Hg2+, Cd2+, and Pb2+ ions respectively. The findings indicate the successful development of an innovative CS/ε-Fe2O3 electrode for the EIS sensing platform. This platform demonstrates notable potential for addressing the critical need for efficient and sensitive EIS sensors capable of detecting a range of hazardous heavy metal ions, including Hg2+, Cd2+, and Pb2+.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

Microbial composition and function in reclaimed mine sites along a reclamation chronosequence become increasingly similar to undisturbed reference sites.

Mine reclamation historically focuses on enhancing plant coverage to improve below and aboveground ecology. However, there is a great need to study the role of soil microorganisms in mine reclamation, particularly long-term studies that track the succession of microbial communities. Here, we investigate the trajectory of microbial communities of mining sites reclaimed between three and 26 years. We used high-throughput amplicon sequencing to characterize the bacterial and fungal communities. We quantified how similar the reclaimed sites were to unmined, undisturbed reference sites and explored the trajectory of microbial communities along the reclamation chronosequence. We also examined the ecological processes that shape the assembly of bacterial communities. Finally, we investigated the functional potential of the microbial communities through metagenomic sequencing. Our results reveal that the reclamation age significantly impacted the community compositions of bacterial and fungal communities. As the reclamation age increases, bacterial and fungal communities become similar to the unmined, undisturbed reference site, suggesting a favorable succession in microbial communities. The bacterial community assembly was also significantly impacted by reclamation age and was primarily driven by stochastic processes, indicating a lesser influence of environmental properties on the bacterial community. Furthermore, our read-based metagenomic analysis showed that the microbial communities' functional potential increasingly became similar to the reference sites. Additionally, we found that the plant richness increased with the reclamation age. Overall, our study shows that both above- and belowground ecological properties of reclaimed mine sites trend towards undisturbed sites with increasing reclamation age. Further, it demonstrates the importance of microbial genomics in tracking the trajectory of ecosystem reclamation.

Surfactant effect on energy storage performance of hydrothermally synthesized Ni3V2O8.

We report a study to improve the ternary oxide Ni3V2O8's electrochemical energy storage capabilities through correct surfactanization during hydrothermal synthesis. In this study, Ni3V2O8nanomaterials were synthesized in three different forms: one with a cationic surfactant (CTAB), one with an anionic surfactant (SLS), and one without any surfactant. FESEM study reveals that all the synthesized Ni3V2O8nanomaterials had a small stone-like morphology. The electrochemical study showed that anionic surfactant-assisted Ni3V2O8(NVSLS) had a maximum of 972 F g-1specific capacitance at 1 A g-1current density, whereas cationic surfactant-assisted Ni3V2O8(NVCTAB) had the lowest specific capacitance of 162 F g-1. The specific capacitance and the capacitance retention of the NVSLS(85% after 4000 cycles) based electrode was much better than that of the NVCTAB(76% after 4000 cycles) based electrode. The improved energy storage properties of the NVSLSelectrode are attributed to its high diffusion coefficient, high surface area, and enriched elemental nickel, as compared to the NVCTABelectrode. All these excellent electrochemical properties of NVSLSelectrode indicates their potential usage in asymmetric supercapacitor application.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.

Laccase-Conjugated Nanostructured ZnFe2O4/rGO-Modified Electrode-Based Interfaces for Electrochemical Impedance Monitoring of Adrenaline: A Promising Biosensor for Management of Neurodegenerative Disorders.

A propitious biosensor for adrenaline (AD) detection in bovine serum albumin (BSA) real samples, which can be used for diagnosis and treatment of neurodegenerative disorders, is reported here. The biosensor consists of a La/ZF/rGO/ITO bioelectrode, which is fabricated by electrophoretic deposition of zinc ferrite/reduced graphene oxide (ZF/rGO) nanohybrid followed by drop casting of laccase (La) enzymes. The material characterization and electrochemical studies revealed that the ZF/rGO nanohybrid enhanced the electroactive surface and facilitated direct electron transfer between the electrode and electrolyte interface, resulting in enhanced electrocatalytic performance. The cyclic voltammetry and electrochemical impedance spectroscopy results asserted that the ZF/rGO nanohybrid decreased the charge-transfer resistance (Rct) and increased the surface adsorption, leading to a high diffusion coefficient (D) of 0.192 cm2/s. The biosensor exhibited a high sensitivity of 0.71 Ω/µM cm2, a good linear range (0.1 to 140 µM with R2 = 0.98), and a low limit of detection (LOD) is 12.5 µM, demonstrating the synergic effect of ZF and rGO in the La/ZF/rGO/ITO bioelectrode with AD. The biosensor also exhibited high selectivity and stability (55 days) in the presence of interfering substances and in BSA samples, with a recovery percentage close to 100 ± 5% RSD, indicating its potential biosensing applications for real-world applications in disease diagnostics, monitoring, and treatment.

Current reversal in polar flock at order-disorder interface.

We studied a system of polar self-propelled particles (SPPs) on a thin rectangular channel designed into three regions of order-disorder-order. The division of the three regions is made on the basis of the noise SPPs experience in the respective regions. The noise in the two wide regions is chosen lower than the critical noise of order-disorder transition and noise in the middle region or interface is higher than the critical noise. This makes the geometry of the system analogous to the Josephson junction (JJ) in solid-state physics. Keeping all other parameters fixed, we study the properties of the moving SPPs in the bulk as well as along the interface for different widths of the junction. On increasing interface width, the system shows an order-to-disorder transition from coherent moving SPPs in the whole system to the interrupted current for large interface width. Surprisingly, inside the interface, we observed the current reversal for intermediate widths of the interface. Such current reversal is due to the strong randomness present inside the interface, which makes the wall of the interface reflecting. Hence, our study gives new interesting collective properties of SPPs at the interface which can be useful to design switching devices using active agents.

Xanthan gum-based copper nano-magnetite doped carbon aerogel: A promising candidate for environmentally friendly catalytic dye degradation.

In this work, a novel copper nano-magnetite doped carbon aerogel (CXMCA) was created utilizing a simple graft co-polymerization approach with xanthan gum (XG) as a template to tackle the agglomeration problem caused by magnetic nanoparticle magnetism. The results indicated that the XG based CXMCA exhibited outstanding magnetic properties (Ms = 36.52 emu/g) as well as strong catalytic activity for the degradation of cationic and anionic dyes. Among all organic dyes, methylene blue and crystal violet (MB, CV) as cationic dyes, as well as congo red and methyl orange (CR, and MO) as anionic dyes, CXMCA demonstrated an exceptional dye degradation rate (8.06 × 10-3 s-1-1.12 × 10-2 s-1) and was highly competent for cationic dyes with degradation (90 %-98 %) as compared to its unsupported magnetic nanoparticles. The formation of CXMCA catalyst is clearly confirmed by the FTIR, XRD, XPS, VSM, SEM & TEM analyses. We report a very effective xanthan gum-based copper nano-magnetite doped carbon aerogel dye scavenger with application in percentage dye degradation and kinetic investigations, as well as a remarkable reusability assay up to 7 repetition cycles. The findings suggested that using biological macromolecules like xanthan gum as a foundation to generate magnetic aerogels might be a good choice for evaluating environmental aspects.

Chitosan stabilized copper iodide nanoparticles enabled nano-bio-engineered platform for efficient electrochemical biosensing of dopamine.

Neurodegenerative disorders are one of the significant challenges to the aging society, as per the United Nations, where 1 in 6 people globally over 65 years of age are expected to suffer by 2050. The exact pathophysiological root of these disorders is although not known adequately, but reduced dopamine (most significant neurotransmitters) levels have been reported in people affected by Parkinson's disease. Sensitive detection and effective monitoring of dopamine can help to diagnose these neurodegenerative disorders at a very early stage, which will help to properly treat these disorders and slow down their progression. Therefore, it is crucial to detect physiological and clinically acceptable amounts of dopamine with high sensitivity and selectivity in basic pathophysiology research, medication, and illness diagnosis. Here in this present investigation, nano-bio-engineered stable chitosan stabilized copper iodide nanoparticles (CS@CuI NPs) were synthesized to engineer the active biosensing platform for developing dopamine biosensors. Initially, the as-synthesized nano-bio-engineered CS@CuI NPs were subjected to its drop-casting onto an Indium tin oxide (ITO) conducting glass substrate. This substrate platform was then utilized to immobilize tyrosinase (Tyr) enzyme by drop-casting to fabricate Tyr/CS@CuI NPs/ITO bioelectrode for the ultrasensitive determination of dopamine. Several techniques were used to characterize the structural, optical, and morphological properties of the synthesized CS@CuI NPs and Tyr/CS@CuI NPs/ITO bioelectrode. Further, the as-prepared bioelectrode was evaluated for its suitability and electrocatalytic behaviour towards dopamine by cyclic voltammetry. A perusal of the electroanalytic results of the fabricated biosensor revealed that under the optimized experimental conditions, Tyr/CS@CuI NPs/ITO bioelectrode exhibits a very high electrochemical sensitivity of 11.64 µA µM-1 cm-2 towards dopamine with the low limit of detection and quantification of 0.02 and 0.386 µM, respectively. In addition, the fabricated bioelectrode was stable up to 46 days with only 4.82 % current loss, reusable till 20 scans, and it also performed effectively while real sample analysis. Therefore, the nano-bio-engineered biosensor platform being reported can determine deficient dopamine levels in a very selective and sensitive manner, which can help adequately manage neurodegenerative disorders, further slowing down the disease progression.

Revolutionizing goat milk gels: A central composite design approach for synthesizing ascorbic acid-functionalized iron oxide nanoparticles decorated alginate-chitosan nanoparticles fortified smart gels.

Goat milk gels (GMGs) are popular food due to their high water content, low-calorie density, appealing taste, texture enhancers, stability, and satiety-enhancing characteristics, making them ideal for achieving food security and zero hunger. The GMGs were optimized using the central composite design matrix of response surface methodology using goat milk powder (35-55 g), whole milk powder (10-25 g), and potato powder (10-15 g) as independent variables. In contrast, complex modulus, flow stress, and forward extrudability were chosen as dependent variables. The maximum value of complex modulus 33670.9 N, good flow stress 7863.6 N, and good extrudability 65.32 N was achieved under optimal conditions. The optimized goat milk gel was fortified with ascorbic acid-coated iron oxide nanoparticle (magnetic nature) decorated alginate-chitosan nanoparticles (AA-MNP@CANPs), making it nutritionally rich in an economically feasible way-the decorated AA-MNP@CANPs characterized for size, shape, crystallinity, surface charge, and optical characteristics. Finally, the optimized fortified smart GMGs were further characterized via Scanning electron microscopy, Rheology, Texture profile analysis, Fourier transforms infrared (FTIR), and X-Ray Diffraction (XRD). The fortified smart GMGs carry more nutritional diversity, targeted iron delivery, and the fundamental sustainability development goal of food security.

RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein. METHODS: Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model. RESULTS: We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance. IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways. Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis. CONCLUSION: Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers.

Bioinspired fabrication of zinc hydroxide-based nanostructure from lignocellulosic biomass Litchi chinensis leaves and its efficacy evaluation on antibacterial, antioxidant, and anticancer activity.

Zinc-based nanostructures are known for their numerous potential biomedical applications. In this context, the biosynthesis of nanostructures using plant extracts has become a more sustainable and promising alternative to effectively replace conventional chemical methods while avoiding their toxic impact. In this study, following a low-temperature calcination process, a green synthesis of Zn-hydroxide-based nanostructure has been performed using an aqueous extract derived from the leaves of Litchi chinensis, which is employed as a lignocellulose waste biomass known to possess a variety of phytocompounds. The biogenic preparation of Zn-hydroxide based nanostructures is enabled by bioactive compounds present in the leaf extract, which act as reducing and capping agents. In order to evaluate its physicochemical characteristics, the produced Zn-hydroxide-based nanostructure has been subjected to several characterization techniques. Further, the multifunctional properties of the prepared Zn-hydroxide-based nanostructure have been evaluated for antioxidant, antimicrobial, and anticancer activity. The prepared nanostructure showed antibacterial efficacy against Bacillus subtilis and demonstrated its anti-biofilm activity as evaluated through the Congo red method. In addition, the antioxidant activity of the prepared nanostructure has been found to be dose-dependent, wherein 91.52 % scavenging activity could be recorded at 200 µg/ml, with an IC50 value of 45.22 µg/ml, indicating the prepared nanostructure has a high radical scavenging activity. Besides, the in vitro cytotoxicity investigation against HepG2 cell lines explored that the as-prepared nanostructure exhibited a higher cytotoxic effect and 73.21 % cell inhibition could be noticed at 25.6 µg/ml with an IC50 of 2.58 µg/ml. On the contrary, it was found to be significantly lower in the case of HEK-293 cell lines, wherein ~47.64 % inhibition could be noticed at the same concentration. These findings might be further extended to develop unique biologically derived nanostructures that can be extensively evaluated for various biomedical purposes.

Expression Profile, Molecular Association, and Clinical Significance of POLD4 in Glioblastoma.

The POLD4 gene encodes a subunit (δ4) of DNA polymerase delta, which is a key enzyme involved in DNA replication and repair. Recent studies have suggested that POLD4 plays a crucial role in developing certain cancers. However, there is a lack of knowledge regarding the role of POLD4 in the context of glioblastoma (GBM). Therefore, in this study we have used various cancer bioinformatics tools to explore the role of POLD4 in glioblastoma. Data from various sources were accessed to analyze POLD4 gene expression and estimate tumor-infiltrating immune cells in glioblastoma. Methylation data were retrieved using the MEXPRESS web browser and analyzed. UALCAN webserver was used to analyze the protein expression of POLD4. Gene correlation and pathway enrichment analysis were performed using cBioPortal and GSEA software, respectively. Afterward, survival analysis was performed. POLD4 was significantly upregulated in glioblastoma at both gene and protein levels in GBM, and ROC curve analysis revealed it as a potential biomarker in glioblastoma. GSEA analysis of TCGA-GBM pan-cancer study exhibited that POLD4 expression was associated with critical pathways, such as interferon-gamma response, G2M checkpoint, inflammatory response, E2F targets, EMT transition, and KRAS signaling pathways. Furthermore, POLD4 expression was positively correlated with DNA methylation at 3 CpG sites, including Cg16509978, with a Pearson correlation coefficient value of 0.398 (p-value ≤ 0.01), while the promoter region had a positive correlation but was not significant. In addition, POLD4 is significantly linked with poor OS, PFS, and DFS. We also found association of POLD4 expression with altered immune cell infiltration. In conclusion, POLD4 is significantly upregulated in glioblastoma and may be used as a potential diagnostic or prognostic biomarker for GBM patients. However, to establish the same a large cohort study is needed. Using TCGA data and various cancer bioinformatics tools mentioned above we observed very high level of gene and protein expression of POLD4 in glioblastoma patients. The expression of POLD4 was significantly correlated with inflammatory and oncogenic pathways and it also has a significant correlation with adverse outcome in patients with glioblastoma.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.

Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy.

An overview of polymer surface coated synthetic quantum dots as therapeutics and sensors applications.

Quantum dots (QDs) are a class of remarkable materials that have garnered significant attention since their initial discovery. It is noteworthy to mention that it took approximately a decade for these materials to be successfully implemented in practical applications. While QDs have demonstrated notable optical properties, it is important to note that these attributes alone have not rendered them a feasible substitute for traditional organic dyes. Furthermore, it is worth noting that the substance under investigation exhibited inherent toxicity and instability in its initial state, primarily due to the presence of a heavy metal core. In the initial stages of research, it was observed that the integration of nanocomposites had a positive impact on the properties of QDs. The discovery of these nanocomposites was motivated by the remarkable properties exhibited by biocomposites found in nature. Recent discoveries have shed light on the potential utilization of QDs as a viable strategy for drug delivery, offering a promising avenue to enhance the efficacy of current pharmaceuticals and pave the way for the creation of innovative therapeutic approaches. The primary objective of this review was to elucidate the distinctive characteristics that render QDs highly suitable for utilization as nanocarriers. In this study, we will delve into the multifaceted applications of QDs as sensing nanoprobes and their utilization in diverse drug delivery systems. The focus of our investigation was directed toward the utilization of QD/polymer composites in sensing applications, with particular emphasis on their potential as chemical sensors, biosensors, and physical sensors.

Gold nanoparticle assisted colorimetric biosensors for rapid polyethylene terephthalate (PET) sensing for sustainable environment to monitor microplastics.

The extremely widespread and ubiquitous nature of plastics, estimated to boost its global production by 26 billion tons till 2050. The large chunks of plastic waste that decomposed down to micro- or nano plastics (MNPs) leads to various ill effects on biological entities. The conventional PET detection methods lack rapid detection of microplastics due to variances in microplastic features, long-drawn-out sample pre-processing procedures and complex instrumentation. Therefore, an instantaneous colorimetric evaluation of microplastic will ensures the simplicity of conducting assays on field. Several nanoparticle-based biosensors that detects proteins, nucleic acids, metabolites operate on either cluster or disperse state of nanoparticle. However, gold nanoparticle (AuNPs) emerges an ideal scaffold for sensory element in lateral flow biosensors due to their simple surface functionalization, unique optoelectronic properties and varied colour spectrum depending on morphologies and aggregation state. In this paper an effort has been made in the form of a hypothesis using in silico tools as a basis to detect polyethylene terephthalate (PET) - most abundant type of microplastic using gold nanoparticle based lateral flow biosensor. We retrieved sequences of PET-binding synthetic peptides and modelled their 3-D structure using I-Tasser server. The best protein model for each peptide sequences are docked with PET monomers - BHET, MHET and other PET polymeric ligands, to evaluate their binding affinities. The synthetic peptide SP 1 (WPAWKTHPILRM) docked with BHET and (MHET)4 exhibits 1.5-fold increases in binding affinity as compared to reference PET anchor peptide Dermaseptin SI (DSI). The GROMACS molecular dynamics simulation studies of synthetic peptide SP 1 - BHET & - (MHET)4 complexes for 50 ns further confirmed the stable binding. RMSF, RMSD, hydrogen bonds, Rg and SASA analysis provides useful structural insights of the SP 1 complexes as compared to reference DSI. Furthermore, SP 1 functionalized AuNP-based colorimetric device was described in detail for detection of PET.