Alleviation of heavy metals chromium, cadmium and lead and plant growth promotion in Vigna radiata L. plant using isolated Pseudomonas geniculata.

Plants exposed to heavy metals (HMs) stress negatively affect their development and production capacity. Chromium (Cr), Cadmium (Cd), and Lead (Pb) are the most common hazardous trace metals in agriculture. The physiological, biochemical, and molecular characteristics of crops are being affected. Phytoremediation is a method to alleviate heavy metals from the contaminated soil. The study aims to evaluate the phytoremediation ability of Vigna radiata L. (mung bean) in the absence and the presence of multi-metal tolerant and plant growth promoting Pseudomonas geniculata strain TIU16A3 isolated from soil of tannery industrial estate, Kolkata, West Bengal, India. The strain was further assessed with increasing concentrations of Cr, Cd, and Pb (10, 20, 40, and 80 µg/mL) when the mung bean plant was a test crop. The strain significantly increased plant growth, chlorophyll content, increased level of antioxidant enzymes such as superoxide dismutase, peroxidase, and catalase, and decreased oxidative stress indicators like H2O2 and electrolyte leakage in the presence of Cr, Cd, and Pb as compared to plants grown in the absence of Pseudomonas geniculata strain. Shoot length responsive gene (Aux/IAA) in the presence of heavy metal alone and Pseudomonas geniculata treated Cd and Cr showed higher relative expression of (Aux/IAA) compared to Pb. Due to these intrinsic abilities, Pseudomonas geniculata strain TIU16A3 can be a plant growth promoter and thus can help in the remediation of heavy metal (Cr, Cd, and Pb) contaminated soil.

An integrated approach to understand the regulatory role of miR-27 family in breast cancer metastasis.

One of the prime reasons of increasing breast cancer mortality is metastasizing cancer cells. Owing to the side effects of clinically available drugs to treat breast cancer metastasis, it is of utmost importance to understand the underlying biogenesis of breast cancer tumorigenesis. In-silico identification of potential RNAs might help in utilizing the miR-27 family as a therapeutic target in breast cancer. The experimentally verified common interacting mRNAs for miR27 family are retrieved from three publicly available databases- TargetScan, miRDB and miRTarBase. Finally on comparing the common genes with HCMDB and GEPIA data, four breast cancer-associated differentially expressed metastatic mRNAs (GATA3, ENAH, ITGA2 and SEMA4D) are obtained. Corresponding to the miR27 family and associated mRNAs, interacting drugs are retrieved from Sm2mir and CTDbase, respectively. The interaction network-based approach was utilized to obtain the hub RNAs and triad modules by employing the 'Cytohubba' and 'MClique' plugins, respectively in Cytoscape. Further, sample-, subclass- and promoter methylation-based expression analyses reveals GATA3 and ENAH to be the most significant mRNAs in breast cancer metastasis having >10% genetic alteration in both METABRIC Vs TCGA datasets as per their oncoprint analysis via cBioPortal. Additionally, survival analysis in Oncolnc reveals SEMA4D as survival biomarker. Interactions among the miR27 family, their target mRNAs and drugs interacting with miRNAs and mRNAs can be extensively explored in both in-vivo and in-vitro setups to assess their therapeutic potential in the diminution of breast cancer.

In situ captured antibacterial action of membrane-incising peptide lamellae.

Developing unique mechanisms of action are essential to combat the growing issue of antimicrobial resistance. Supramolecular assemblies combining the improved biostability of non-natural compounds with the complex membrane-attacking mechanisms of natural peptides are promising alternatives to conventional antibiotics. However, for such compounds the direct visual insight on antibacterial action is still lacking. Here we employ a design strategy focusing on an inducible assembly mechanism and utilized electron microscopy (EM) to follow the formation of supramolecular structures of lysine-rich heterochiral ß3-peptides, termed lamellin-2K and lamellin-3K, triggered by bacterial cell surface lipopolysaccharides. Combined molecular dynamics simulations, EM and bacterial assays confirmed that the phosphate-induced conformational change on these lamellins led to the formation of striped lamellae capable of incising the cell envelope of Gram-negative bacteria thereby exerting antibacterial activity. Our findings also provide a mechanistic link for membrane-targeting agents depicting the antibiotic mechanism derived from the in-situ formation of active supramolecules.

Incorporating silver nanoparticles into electrospun nanofibers of casein/polyvinyl alcohol to develop scaffolds for tissue engineering.

Developing novel antimicrobial wound dressings that have the potential to address the challenges associated with chronic wounds is highly imperative in providing effective infection control and wound healing support. Biocompatible electrospun nanofibers with their high porosity and surface area enabling efficient drug loading and delivery have been investigated in this regard as viable candidates for chronic wound care. Here, we design Casein/Polyvinyl alcohol (CAN/PVA) nanofibers reinforced with silver nanoparticles (Ag NPs) by the electrospinning technique to develop diabetic wound healing scaffolds. The prepared samples were characterized using spectroscopic and electron microscopic techniques. The biocompatibility of the polymer samples were assessed using 3 T3 fibroblast cell lines and the maximum cell viability was found to 95 % at a concentration of 50 µg/mL for the prepared nanofibers. Scratch assay tests were also performed to analyze the wound healing activity of the nanofibers wherein they demonstrated increased migration and proliferation of fibroblast 3 T3 cells. Moreover, these nanofibers also exhibit antibacterial efficiency against Gram-negative bacteria, Escherichia coli (E.coli). Therefore, the antimicrobial nature of the electrospun nanofibers coupled with their moisture absorption properties and wound healing ability render them as effective materials for wound dressing applications.

Correction: Srinivasan Rajsri et al. Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection. Cancers 2023, 15, 2866.

In the original publication [...].

Multi-OMICS approaches in cancer biology: New era in cancer therapy.

Innovative multi-omics frameworks integrate diverse datasets from the same patients to enhance our understanding of the molecular and clinical aspects of cancers. Advanced omics and multi-view clustering algorithms present unprecedented opportunities for classifying cancers into subtypes, refining survival predictions and treatment outcomes, and unravelling key pathophysiological processes across various molecular layers. However, with the increasing availability of cost-effective high-throughput technologies (HTT) that generate vast amounts of data, analyzing single layers often falls short of establishing causal relations. Integrating multi-omics data spanning genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes offers unique prospects to comprehend the underlying biology of complex diseases like cancer. This discussion explores algorithmic frameworks designed to uncover cancer subtypes, disease mechanisms, and methods for identifying pivotal genomic alterations. It also underscores the significance of multi-omics in tumor classifications, diagnostics, and prognostications. Despite its unparalleled advantages, the integration of multi-omics data has been slow to find its way into everyday clinics. A major hurdle is the uneven maturity of different omics approaches and the widening gap between the generation of large datasets and the capacity to process this data. Initiatives promoting the standardization of sample processing and analytical pipelines, as well as multidisciplinary training for experts in data analysis and interpretation, are crucial for translating theoretical findings into practical applications.

Halotolerant Citrobacter sp. remediates salinity stress and promotes the growth of Vigna radiata (L) by secreting extracellular polymeric substances (EPS) and biofilm formation: a novel active cell for microbial desalination cell (MDC) / Citrobacter sp. halotolerante. remedia el estrés salino y promueve el crecimiento de Vigna radiata (L) mediante la secreción de sustancias poliméricas extracelulares (EPS) y la formación de biopelículas: una nueva célula activa para la célula microbiana de desalinización (MDC)

To address soil salinization and its impact on crop production, microbial desalination cells (MDCs) offer a promising solution. These bioelectrochemical systems integrate desalination and wastewater treatment through microbial activity. A halotolerant beneficial bacterial strain called Citrobacter sp. strain KUT (CKUT) was isolated from India’s salt desert Run of Kutch, Gujrat, highlighting its potential application in combating soil salinization. CKUT exhibits high salt tolerance and has the ability to produce extracellular polymeric substances (EPS) at a concentration of 0.04 mg/ml. It forms biofilm that enable it to withstand up to 10% NaCl concentration. Additionally, CKUT shows promise in remediating salinity levels, reducing it from 4.5 to 2.7 gL−1. These characteristics are driven by biofilm formation and EPS production. In an experiment where V. radiata L. seedlings were inoculated with CKUT, the treated plants exhibited enhanced chlorophyll content, growth, and overall plant characteristics compared to seedlings treated with sodium chloride (NaCl). These improvements included increased shoot length (150 mm), root length (40 mm), and biomass. This indicates that CKUT treatment has the potential to enhance the suitability of V. radiata and other crops for cultivation in saline lands, effectively addressing the issue of soil salinization. Furthermore, integrating CKUT into microbial desalination cells (MDCs) offers an opportunity for freshwater production from seawater, contributing to sustainable agriculture by promoting improved crop growth and increased yield in areas prone to salinity.(AU)

Cytomegalovirus Reactivation as a Risk Factor for All-Cause Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation: Experience Over Two Decades from a Tertiary Referral Center in India.

The aim of the study was to analyse the burden of cytomegalovirus (CMV) disease in children undergoing hematopoietic stem cell transplantation (HSCT) and its correlation with all-cause mortality. We performed a retrospective study in children up to 18 years of age who underwent allogeneic HSCT between February 2002 to December 2021 in the pediatric blood and marrow transplantation unit. A total of 1035 patients were included where five hundred forty-three (52.4%) patients underwent matched family donor (MFD) HSCT, 213 (20.5%) underwent matched unrelated donor (MUD) HSCT; 279 (26.9%) underwent haploidentical HSCT (T cell replete in 213 and T cell depleted in 66 patients). CMV reactivation was documented in 258 (24.9% patients). CMV was seen in 39 (7.2%) MFD, 77 (36.1%) MUD, 106 T cell replete (49.7%) and 36 T cell depleted (54.5%) transplants. CMV reactivation was predominantly documented in those where donor and recipient were positive (D + /R +) for CMV serostatus (77%)) prior to HSCT. Overall mortality rate was significantly higher in the CMV positive group (103/258, 39.9%), as compared to the CMV negative group (152/777, 19.6%) (p value = 0.0001). CMV was the direct cause of death in 13/1035 children (1.2%). GvHD as a cause of death was found to be significantly higher among those with CMV (n = 32) as compared to those without CMV (n = 14) (35.6 versus 9%, p value = 0.0001). The incidence of CMV reactivation was noted in 25% of HSCT recipients, and predominantly in haploidentical HSCTs. CMV reactivation was shown to significantly impact all-cause mortality and there was a significantly increased risk of mortality due to GvHD among those with CMV reactivation.

Halotolerant Citrobacter sp. remediates salinity stress and promotes the growth of Vigna radiata (L) by secreting extracellular polymeric substances (EPS) and biofilm formation: a novel active cell for microbial desalination cell (MDC).

To address soil salinization and its impact on crop production, microbial desalination cells (MDCs) offer a promising solution. These bioelectrochemical systems integrate desalination and wastewater treatment through microbial activity. A halotolerant beneficial bacterial strain called Citrobacter sp. strain KUT (CKUT) was isolated from India's salt desert Run of Kutch, Gujrat, highlighting its potential application in combating soil salinization. CKUT exhibits high salt tolerance and has the ability to produce extracellular polymeric substances (EPS) at a concentration of 0.04 mg/ml. It forms biofilm that enable it to withstand up to 10% NaCl concentration. Additionally, CKUT shows promise in remediating salinity levels, reducing it from 4.5 to 2.7 gL-1. These characteristics are driven by biofilm formation and EPS production. In an experiment where V. radiata L. seedlings were inoculated with CKUT, the treated plants exhibited enhanced chlorophyll content, growth, and overall plant characteristics compared to seedlings treated with sodium chloride (NaCl). These improvements included increased shoot length (150 mm), root length (40 mm), and biomass. This indicates that CKUT treatment has the potential to enhance the suitability of V. radiata and other crops for cultivation in saline lands, effectively addressing the issue of soil salinization. Furthermore, integrating CKUT into microbial desalination cells (MDCs) offers an opportunity for freshwater production from seawater, contributing to sustainable agriculture by promoting improved crop growth and increased yield in areas prone to salinity. HIGHLIGHTS : • Soil salinization reduces crop yield, including Vigna radiata L. • Citrobacter sp. strain KUT (CKUT) is a halotolerant bacterium isolated from the salt desert Run of Kutch, Gujarat, which can tolerate high salt concentrations. • CKUT mitigates salinity by producing extracellular polymeric substances (EPS) and forming biofilms. • CKUT treatment demonstrated increased plant growth, biomass, and chlorophyll content under salinity stress, showcasing its potential in microbial desalination cell (MDC) for enhancing crop yield in salinized soils.

Understanding crosstalk of organ tropism, tumor microenvironment and noncoding RNAs in breast cancer metastasis.

Cancer metastasis is one of the major clinical challenges worldwide due to limited existing effective treatments. Metastasis roots from the host organ of origin and gradually migrates to different regional and distant organs. In different breast cancer subtypes, different organs like bones, liver, lungs and brain are targeted by the metastatic tumor cells. Cancer renders mortality to their respective metastasizing sites like bones, brain, liver, and lungs. Metastatic breast cancers are best treated and managed if detected at an early stage. Metastasis is regulated by various molecular activators and suppressors. The conventional theory of 'seed and soil' states that metastatic tumor cells move to tumor microenvironment that has favorable conditions like blood flow for them to grow just like seeds grows when planted in fertile land. Additionally, different coding as well as non-coding RNAs play a very significant role in the process of metastasis by modulating their expression levels leading to a crosstalk of various tumorigenic cascades. Treatments for metastasis is also very critical in controlling this lethal process. Detecting breast cancer metastasis at an early stage is crucial for managing and predicting metastatic progression. In this review, we have compiled several factors that can be targeted to manage the onset and gradual stages of breast cancer metastasis.

Multidimensional computational study to understand non-coding RNA interactions in breast cancer metastasis.

Metastasis is a major breast cancer hallmark due to which tumor cells tend to relocate to regional or distant organs from their organ of origin. This study is aimed to decipher the interaction among 113 differentially expressed genes, interacting non-coding RNAs and drugs (614 miRNAs, 220 lncRNAs and 3241 interacting drugs) associated with metastasis in breast cancer. For an extensive understanding of genetic interactions in the diseased state, a backbone gene co-expression network was constructed. Further, the mRNA-miRNA-lncRNA-drug interaction network was constructed to identify the top hub RNAs, significant cliques and topological parameters associated with differentially expressed genes. Then, the mRNAs from the top two subnetworks constructed are considered for transcription factor (TF) analysis. 39 interacting miRNAs and 1641 corresponding TFs for the eight mRNAs from the subnetworks are also utilized to construct an mRNA-miRNA-TF interaction network. TF analysis revealed two TFs (EST1 and SP1) from the cliques to be significant. TCGA expression analysis of miRNAs and lncRNAs as well as subclass-based and promoter methylation-based expression, oncoprint and survival analysis of the mRNAs are also done. Finally, functional enrichment of mRNAs is also performed. Significant cliques identified in the study can be utilized for identification of newer therapeutic interventions for breast cancer. This work will also help to gain a deeper insight into the complicated molecular intricacies to reveal the potential biomarkers involved with breast cancer progression in future.

Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by an abundance of incompletely matured or immature clonally derived hematopoietic precursors called leukemic blasts. Rare leukemia stem cells (LSCs) that can self-renew as well as give rise to leukemic progenitors comprising the bulk of leukemic blasts are considered the cellular reservoir of disease initiation and maintenance. LSCs are widely thought to be relatively resistant as well as adaptive to chemotherapy and can cause disease relapse. Therefore, it is imperative to understand the molecular bases of LSC forms and functions during different stages of disease progression, so we can more accurately identify these cells and design therapies to target them. Irrespective of the morphological, cytogenetic, and cellular heterogeneity of AML, the uniform, singularly important and independently significant prognosticator of disease response to therapy and patient outcome is measurable or minimal residual disease (MRD) detection, defined by residual disease detection below the morphology-based 5% blast threshold. The importance of LSC identification and frequency estimation during MRD detection, in order to make MRD more effective in predicting disease relapse and modifying therapeutic regimen is becoming increasingly apparent. This review focuses on summarizing functional and cellular composition-based LSC identification and linking those studies to current techniques of MRD detection to suggest LSC-inclusive MRD detection as well as outline outstanding questions that need to be addressed to improve the future of AML clinical management and treatment outcomes.

A teenager with ophthalmoparesis and dysphagia.

The pharyngeal-cervical-brachial (PCB) variant is a rare presentation of Guillain-Barré syndrome (GBS), and there is a handful of case reports that overlap with the Miller-Fisher syndrome (MFS) variant of GBS. This overlap produces varied symptoms that may be confusing and challenging for physicians to diagnose timely and start appropriate treatment. In this article, we present a case report and review of the rare overlap of the PCB variant with the MFS variant of GBS.

Pathogenic Mechanisms in Acute Myeloid Leukemia.

OPINION STATEMENT: Acute myeloid leukemia (AML) is the most common form of leukemia in adults, leading to the highest number of annual leukemia-associated deaths in the USA. Although most AML patients initially enter remission following induction therapy, most eventually relapse, underscoring the unmet need for more effective therapies. In recent years, novel high-throughput sequencing techniques, and mouse and human models of disease have increased our understanding of the molecular mechanisms that lead to AML. Leukemogenic mechanisms can be broadly classified into two types-cell-intrinsic and cell-extrinsic. Cell-intrinsic mechanisms include an array of genetic and epigenetic alterations that lead to dysregulated gene expression and function in hematopoietic stem/progenitor cells, leading to their increased fitness and ultimately, malignant transformation. Extrinsic mechanisms include both hematopoietic and non-hematopoietic stromal components of the leukemic microenvironment that interact with pre-leukemic and leukemic clones to promote their survival, self-renewal, and/or resistance to therapy. Through the individual and concerted action of these factors, pre-leukemic clones acquire the changes necessary for leukemic transformation. In addition, following therapy, specific leukemic clones are selected for that eventually re-initiate disease. Improving our understanding of these cell-intrinsic and cell-extrinsic mechanisms will provide novel opportunities to treat AML as well as prevent the development of disease.

Leukotrienes promote stem cell self-renewal and chemoresistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by poor clinical outcomes due to high rates of relapse following standard-of-care induction chemotherapy. While many pathogenic drivers have been described in AML, our understanding of the molecular mechanisms mediating chemotherapy resistance remains poor. Therefore, we sought to identify resistance genes to induction therapy in AML and elucidated ALOX5 as a novel mediator of resistance to anthracycline-based therapy. ALOX5 is transcriptionally upregulated in AML patient blasts in comparison to normal hematopoietic stem/progenitor cells (HSPCs) and ALOX5 mRNA, and protein expression is increased in response to induction therapy. In vitro, and in vivo genetic, and pharmacologic perturbation studies confirm that ALOX5 positively regulates the leukemogenic potential of AML LSCs, and its loss does not significantly affect the function of normal HSPCs. ALOX5 mediates resistance to daunorubicin (DNR) and promotes AML cell survival and maintenance through its leukotriene (LT) synthetic capacity, specifically via modulating the synthesis of LTB4 and its binding to LTB receptor (BLTR). Our study reveals a previously unrecognized role of LTs in AML pathogenesis and chemoresistance, whereby inhibition of ALOX5 mediated LTB4 synthesis and function could be combined with standard chemotherapy, to enhance the overall therapeutic efficacy in AML.

Numerical Modelling and Analytical Comparison of Delamination during Cryogenic Drilling of CFRP.

Carbon-Fibre-Reinforced Polymers (CFRPs) have seen a steady rise in modern industrial applications due to their high strength-to-weight ratio and corrosion resistance. However, their potential is being hindered by delamination which is induced on them during machining operations. This has led to the adoption of new and innovative techniques like cryogenic-assisted machining which could potentially help reduce delamination. This study is aimed at investigating the effect of cryogenic conditions on achieving better hole quality with reduced delamination. In this paper, the numerical analysis of the drilling of CFRP composites is presented. Drilling tests were performed experimentally for validation purposes. The effects of cooling conditions and their subsequent effect on the thrust force and delamination were evaluated using ABAQUS/CAE. The numerical models and experimental results both demonstrated a significant reduction in the delamination factor in CFRP under cryogenic drilling conditions.