ABSTRACT
Carbon quantum dots derived from mango leaves exhibited red fluorescence. These negatively charged particles underwent coating with the positively charged lipid molecule N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA). However, the bioconjugate displayed reduced uptake compared to the standalone mQDs in cancer cells (SUM 159A), and increased uptake in case of non-cancerous (RPE-1) cells. Upon in vitro testing, the bioconjugate demonstrated a mitigating effect on the individual toxicity of both DOTMA and mQDs in SUM-159 (cancerous cells). Conversely, it exhibited a proliferative effect on RPE-1 (normal cells).
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Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson's disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA TD as a carrier for dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate that these dopamine-loaded DNA TD nanostructures enhanced cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson's disease and other neurological disorders.
Subject(s)
DNA , Dopamine , Drug Carriers , Zebrafish , Dopamine/chemistry , Dopamine/metabolism , Dopamine/pharmacology , Animals , DNA/chemistry , DNA/metabolism , Humans , Cell Line, Tumor , Drug Carriers/chemistry , Nanostructures/chemistry , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Molecular Dynamics Simulation , Nervous System Diseases/drug therapy , Nervous System Diseases/metabolism , Cell Differentiation/drug effects , Blood-Brain Barrier/metabolismABSTRACT
Studies in fruit flies, Drosophila melanogaster, have observed considerable variation in the effect of dietary protein restriction (PR) on various fitness traits. In addition, not only are there inconsistent results relating lifespan to stress resistance, but also the long-term effects of PR are unexplored. We study PR implementation across generations (long term) hypothesizing that it will be beneficial for fitness traits, stress resistance and storage reserves due to nutritional plasticity transferred by parents to offspring in earlier Drosophila studies. By imposing two concentrations of PR diets (50% and 70% of control protein) from the pre-adult and adult (age 1 day) stages of the flies, we assessed the stage-specific and long-term effect of the imposed PR. All long-term PR flies showed increased resistance against the tested stressors (starvation, desiccation, H2O2-induced oxidative stress). In addition, we also found long-term PR-induced increased stress resistance across generations. The PR flies also possessed higher protein and triglyceride (TG) content, reduced glucose and unaffected glycogen levels. We also assayed the effect of returning the PR flies to control (AL) food for a single generation and assessed their biochemical parameters to witness the transient PR effect. It was seen that TG content upon reversal was similar to AL flies except for PRI70 males; however, the glucose levels of PR males increased, while they were consistently lower in females. Taken altogether, our study suggests that long-term PR implementation contributes to increased stress resistance and was found to influence storage reserves in D. melanogaster.
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This study delves into the innovative approach of enhancing the efficiency and stability of all-inorganic perovskite solar cells (I-PSCs) through the strategic incorporation of thiocyanate (SCN-) ions via pseudohalide-based ionic liquid (IL) configurations. This straightforward methodology has exhibited captivating advancements in the kinetics of crystallization as well as the optoelectronic characteristics of the resulting perovskite films. These developments hold the promise of enhancing not only the quality and uniformity of the films but also aspects such as band alignment and the efficacy of charge transfer mechanisms. Calculation results corroborate that the incorporation of 1-butyl-3-methylimidazolium thiocyanate (BmimSCN) led to a significant redistribution of electron state density and enhanced electron-donating properties, indicating a substantial electron transfer between the perovskite material and the IL. Notably, the engineered devices demonstrate a remarkable efficiency surpassing 15%, a substantial enhancement attributed to the synergistic effects of the SCN- ion. Additionally, this approach offers inherent stability benefits, thereby addressing a significant challenge in I-PSC technology. This IL maintains >90% of the initial efficiency after 600 h, while the control device decreased to <20% of its initial value after only 100 h. 1-butyl-3-methylimidazolium iodide (BmimI) is also employed to further investigate the effects of SCN- ions on device performance.
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Neuropsychiatric disorders are mainly concerned with the behavioural, emotional and cognition symptoms that may be due to disturbed cerebral functions or extracerebral disease. Klotho protein is an antiaging protein that is mostly associated with cognitive changes in these disorders and thus this meta-analysis is conducted in order to find Klotho proteins association with these disorders. We searched related topics in pubmed, by using the key word i.e. Klotho and related disorder from neuropsychiatry e.g. Klotho levels and schizophrenia, Klotho levels and parkinsonism etc. Total 82 studies were found till 9th February 2021 after extensive search and 10 studies were selected for further analysis. The meta-analysis of studies was performed using the Random effect model. The forest plot represented each study in the meta-analysis, so as to make the comparison of SMD value across studies. The meta-analysis outcome demonstrated that overall schizophrenia had higher klotho levels as compared with bipolar disorder, psychosocial stress, parkinsonism, multiple sclerosis, depression, Alzheimer's disease, and healthy controls, followed by MS. The meta-analysis also found that bipolar disorder and Alzheimer's disease were associated with low klotho levels as compared to schizophrenia. The results indicate a significant association of the klotho levels and schizophrenia. Further studies are needed to characterize the potential biological roles of klotho levels in psychiatric disorders.
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Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants frequently detected in drinking water worldwide. Reports linking PFAS exposure to cardiovascular disease have increased significantly in recent years. Furthermore, women appear to be more susceptible to the adverse effects of PFAS. However, the potential role of ovaries in the increased vulnerability of females to PFAS-related health effects remains unknown. In this study, we investigated the impact of perfluorooctane sulfonate (PFOS), a prominent PFAS, on the cardiovascular function in female rats with intact ovaries and ovariectomized (OVX) females. Bilateral OVX or sham surgeries were performed in 8-week-old female SD rats. Following recovery from surgeries, the rats were given drinking water containing 50 µg/mL of PFOS for 3 weeks. Control groups received PFOS-free water. PFOS exposure significantly reduced body weight but increased blood pressure similarly in both intact and OVX rats. Echocardiography analysis revealed that PFOS exposure decreased cardiac output, end-systolic volume, and end-diastolic volume in intact but not OVX rats. Vascular function studies demonstrated that PFOS equally reduced endothelium-dependent and -independent relaxation responses in intact and OVX rats. The endothelium-independent contractile responses were more pronounced in both intact and OVX rats. eNOS protein levels were similarly decreased in both intact and OVX rats. In conclusion, PFOS affects cardiac function through hormone-dependent mechanisms, while vascular function is impaired independent of ovarian status, indicating an intricate interplay between PFOS exposure, ovarian status, and cardiovascular function.
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Background: Gestational intermittent hypoxia (GIH), a hallmark of maternal obstructive sleep apnea, sex-differentially causes hypertension and endothelial dysfunction in adult male offspring but not in females. This study investigated whether the GIH-exposed female offspring, a "protected" group against the hypertensive effects of maternal GIH exposure, exhibit increased susceptibility to hypertension and cardiovascular dysfunction when fed a high-fat high-sucrose (HFHS) diet and whether this effect could be reversed by pharmacological intervention activating the angiotensin II type 2 receptor (AT2R). Methods: Female offspring of control and GIH-exposed (10.5% O2, 8 h/d, E10-21) dams were assigned either an HFHS diet or a standard diet from 12 weeks of age. Blood pressure was monitored. At 28 weeks, a systemic CGP42112 (AT2R agonist) or saline infusion was administered through the osmotic pump. At 30 weeks, the heart was weighed and collected for H&E staining, mesenteric arteries for vascular reactivity assessment and protein analysis, and plasma for ELISA. Results: The HFHS diet induced similar increases in body weight gain and blood pressure in control and GIH female offspring. HFHS feeding did not affect heart structure, but impaired endothelial-dependent vascular relaxation with associated decreased AT2R and eNOS expression and reduced plasma bradykinin levels in both control and GIH offspring. CGP42112 administration effectively mitigated HFHS-induced hypertension and endothelial dysfunction only in control offspring, accompanied by restored AT2R, eNOS, and bradykinin levels, but not in the GIH counterparts. Conclusion: These findings suggest that GIH induces endothelial dysfunction and AT2R insensitivity in female offspring exposed to an HFHS diet.
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Microplastics have been ubiquitous in our environment for decades, and numerous studies have revealed their extensive dispersion, reaching far beyond the surface of the land, soil, aquatic ecosystems. They have infiltrated the food-chain, the food web, even the air we breathe, as well as the water we drink. Microplastics have been detected in the food we consume, acting as vectors for hazardous chemicals that adhere to their hydrophobic surfaces. This can result in the transfer of these chemicals to the aquatic life, posing a threat to their well-being. The release of microplastics into different environmental settings can give rise to various eco-toxicological implications. The substantial body of literature has led scientists to the consensus that microplastic pollution is a global problem with the potential to impact virtually any type of ecosystem. This paper aims to discuss crucial information regarding the occurrence, accumulation, and ecological effects of microplastics on organisms. It also highlights the new and emerging disease named "Plasticosis" that is directly linked to microplastics and its toxicological effects like permanent scarring and long-term inflammation in the digestive system of the seabirds. By comprehending the behaviour of these microplastic pollutants in diverse habitats and evaluating their ecological consequences, it becomes possible to facilitate a better understanding of this toxicological issue.
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BACKGROUND: Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. OBJECTIVE: This study aimed to investigate the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats and examine the underlying mechanisms. METHODS: Pregnant rats were administered sFlt-1 (6 µg/kg/day, intravenously) or vehicle from gestation day (GD) 12 to 20. A subset of these groups received GYY4137 (an H2S donor, 50 mg/kg/day, subcutaneously) from GD 16 to 20. Serum H2S levels, mean arterial blood pressure (CODA tail-cuff), uterine artery blood flow (ultrasonography), vascular reactivity to vasopressors and endothelial-dependent relaxation (myography), endothelial nitric oxide synthase (eNOS) protein expression in uterine arteries (Western blotting) were assessed. In addition, maternal weight gain, as well as fetal and placental weights, were measured. RESULTS: Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. CONCLUSION: sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.
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BACKGROUND: Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and emerging risk factors for reproductive health. Although epidemiological evidence supports the link between these substances and male infertility, their specific effects on male fertility remain poorly understood. OBJECTIVES: Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and prominent PFAS, on bull sperm protein phosphorylation, a post-translational modification process governing sperm functionality and fertility. METHODS: We exposed bull sperm to PFOS at 10 µM (average population level) and 100 µM (high-exposure level), and analyzed global proteome and phosphoproteome profile by TMT labeling and NanoLC-MS/MS. We also measured sperm fertility functions by flow cytometry. RESULTS: PFOS at 10 µM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 µM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, 4 proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both the proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm as well as reduced sperm motility, viability, calcium, and membrane potential and increased mitochondrial ROS in a dose-dependent manner. CONCLUSIONS: This study shows that PFOS exposure adversely impacts phosphorylation of proteins critical for bull sperm function and fertilization. Moreover, the concentration of PFOS influences the severity of these effects. The comprehensive bull sperm phosphoproteomics data from this study can help us understand the molecular mechanisms of environmental exposure-related male infertility.
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Introduction and importance: The SARS-CoV-2 is the source of COVID-19, a respiratory disease. It typically manifests as restricted pulmonary symptoms, but autoimmune dysfunction might occasionally show up. A COVID-19 infection may cause a multi-system connective tissue disease known as systemic sclerosis (SSc). In patients who recovered from COVID-19, autoimmunity may have multiple underlying causes. Case presentation: The authors report the case of a 68-year-old female who, 1 month after contracting COVID-19, complained of dyspnoea and muscle exhaustion. The patient was treated for post-COVID syndrome. She developed symptoms of chronic dyspnoea, pale fingers, pursed lips, trouble chewing and swallowing, and muscle weakness after 7 weeks. A chest high-resolution computerised tomography (HRCT) scan suggested interstitial lung disease. Clinical characteristics and an autoantibody profile containing anti-Ro 52 and anti-centromere antibodies pointed towards SSc. She was treated with azathioprine and prednisolone at a reduced dosage, and she is now stable with monthly follow-ups. Clinical discussion: COVID-19 might induce cytokine storms and immunological dysregulation, ultimately culminating in autoimmune manifestations. Several autoantibodies are observed in autoimmune illnesses in post-COVID-19 infection patients. Our situation is distinct because SSc following a COVID-19 infection is not commonly seen as an autoimmune illness. Conclusion: The number of patients with rare autoimmune diseases, like SSc, following COVID-19 has been rising. Therefore, we should consider the possibility of autoimmune disease when looking into a patient who presents strangely or has developed new symptoms after COVID and should contact the patient's management immediately.
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Metformin (MET) is a preferred drug for the treatment of type 2 diabetes mellitus. Recent studies show that apart from its blood glucose-lowering effects, it also inhibits the development of various tumours, by inducing autophagy. Various studies have confirmed the inhibitory effects of MET on cancer cell lines' propagation, migration, and invasion. The objective of the study was to comprehensively review the potential of MET as an anticancer agent, particularly focusing on its ability to induce autophagy and inhibit the development and progression of various tumors. The study aimed to explore the inhibitory effects of MET on cancer cell proliferation, migration, and invasion, and its impact on key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and PI3K. This review noted that MET exerts its anticancer effects by regulating key signalling pathways such as phosphoinositide 3-kinase (PI3K), LC3-I and LC3-II, Beclin-1, p53, and the autophagy-related gene (ATG), inhibiting the mTOR protein, downregulating the expression of p62/SQSTM1, and blockage of the cell cycle at the G0/G1. Moreover, MET can stimulate autophagy through pathways associated with the 5' AMPK, thereby inhibiting he development and progression of various human cancers, including hepatocellular carcinoma, prostate cancer, pancreatic cancer, osteosarcoma, myeloma, and non-small cell lung cancer. In summary, this detailed review provides a framework for further investigations that may appraise the autophagy-induced anticancer potential of MET and its repurposing for cancer treatment.
Subject(s)
AMP-Activated Protein Kinases , Autophagy , Metformin , Neoplasms , Signal Transduction , TOR Serine-Threonine Kinases , Metformin/pharmacology , Humans , Autophagy/drug effects , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , AMP-Activated Protein Kinases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , AnimalsABSTRACT
One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.
Subject(s)
Carbon , Cell Differentiation , Dopamine , Quantum Dots , Zebrafish , Quantum Dots/chemistry , Humans , Carbon/chemistry , Carbon/pharmacology , Dopamine/metabolism , Dopamine/chemistry , Animals , Cell Differentiation/drug effects , Neurons/drug effects , Neurons/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Particle Size , Materials Testing , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Optical Imaging , Cell Survival/drug effects , Cell Line, TumorABSTRACT
Lung cancer (LC) is the second most prevalent cancer worldwide and a leading cause of cancer-related deaths. Recent technological advancements have revealed that the lung microbiome, previously thought to be sterile, is host to various microorganisms. The association between the lung microbiome and LC initiation, progression, and metastasis is complex and contradictory. However, disruption in the homeostasis of microbiome compositions correlated with the increased risk of LC. This review summarises current knowledge on the most recent developments and trends in lung cancer-related microbiota or microbial components. This manuscript aims to provide information on this rapidly evolving field while giving context to the general role of the lung microbiome in LC. In addition, this review briefly discussed the causative association of lung microbiome with LC. We will review the mechanisms of how lung microbiota influences carcinogenesis, focusing on microbiota dysbiosis. Moreover, we will also discuss the host-microbiome interaction as host-microbiota plays a crucial role in stimulating and regulating the immune response. Finally, we provide information on the diagnostic role of the microbiome in LC. It aims to offer an overview of the lung microbiome as a predictive and diagnostic biomarker in LC.
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Efficiently mapping of cell types in situ remains a major challenge in spatial transcriptomics. Most spot deconvolution tools ignore spatial coordinate information and perform extremely slow on large datasets. Here, we introduce SpatialPrompt, a spatially aware and scalable tool for spot deconvolution and domain identification. SpatialPrompt integrates gene expression, spatial location, and single-cell RNA sequencing (scRNA-seq) dataset as reference to accurately infer cell-type proportions of spatial spots. SpatialPrompt uses non-negative ridge regression and graph neural network to efficiently capture local microenvironment information. Our extensive benchmarking analysis on Visium, Slide-seq, and MERFISH datasets demonstrated superior performance of SpatialPrompt over 15 existing tools. On mouse hippocampus dataset, SpatialPrompt achieves spot deconvolution and domain identification within 2 minutes for 50,000 spots. Overall, domain identification using SpatialPrompt was 44 to 150 times faster than existing methods. We build a database housing 40 plus curated scRNA-seq datasets for seamless integration with SpatialPrompt for spot deconvolution.
Subject(s)
Gene Expression Profiling , Transcriptome , Animals , Mice , Gene Expression Profiling/methods , Single-Cell Analysis/methods , Software , Sequence Analysis, RNA/methods , Hippocampus/metabolismABSTRACT
This study introduces a novel approach centered around the design and synthesis of an interfacial passivating layer in perovskite solar cells (PSCs). This architectural innovation is realized through the development of a specialized material, termed dithiafulvene end-capped Spiro[fluorene-9,9'-xanthene], denoted by the acronym AF32. In this design architecture, dithiafulvene is thoughtfully attached to the spiroxanthene fluorene core with phenothiazine as the spacer unit, possessing multiple alkyl chains. AF32 passivates interfacial defects by coordinating the sulfur constituents of the phenothiazine and dithiafulvene frameworks to the uncoordinated Pb2+ cations on the surface of the perovskite film, and the alkyl chains construct a hydrophobic environment, preventing moisture from entering the hydrophilic perovskite layer and improving the long-term stability of PSCs. Furthermore, this conductive interlayer facilitates hole transport in PSCs due to its well-aligned molecular orbital levels. Such improvements translated into an enhanced power conversion efficiency (PCE) of 22.6% for the device employing 1.5 mg/mL AF32, and it maintained 85% of its initial PCE after more than 1800 h under ambient conditions [illumination and 45 ± 5% relative humidity (RH)]. This study not only marks progress in photovoltaic technology but also expands our understanding of manipulating interfacial properties for optimized device performance and stability.
ABSTRACT
AIMS: This study aimed to isolate plant growth and drought tolerance-promoting bacteria from the nutrient-poor rhizosphere soil of Thar desert plants and unravel their molecular mechanisms of plant growth promotion. METHODS AND RESULTS: Among our rhizobacterial isolates, Enterobacter cloacae C1P-IITJ, Kalamiella piersonii J4-IITJ, and Peribacillus frigoritolerans T7-IITJ, significantly enhanced root and shoot growth (4-5-fold) in Arabidopsis thaliana under PEG-induced drought stress. Whole genome sequencing and biochemical analyses of the non-pathogenic bacterium T7-IITJ revealed its plant growth-promoting traits, viz., solubilization of phosphate (40-73 µg/ml), iron (24 ± 0.58 mm halo on chrome azurol S media), and nitrate (1.58 ± 0.01 µg/ml nitrite), along with production of exopolysaccharides (125 ± 20 µg/ml) and auxin-like compounds (42.6 ± 0.05 µg/ml). Transcriptome analysis of A. thaliana inoculated with T7-IITJ and exposure to drought revealed the induction of 445 plant genes (log2fold-change > 1, FDR < 0.05) for photosynthesis, auxin and jasmonate signalling, nutrient uptake, redox homeostasis, and secondary metabolite biosynthesis pathways related to beneficial bacteria-plant interaction, but repression of 503 genes (log2fold-change < -1) including many stress-responsive genes. T7-IITJ enhanced proline 2.5-fold, chlorophyll 2.5-2.8-fold, iron 2-fold, phosphate 1.6-fold, and nitrogen 4-fold, and reduced reactive oxygen species 2-4.7-fold in plant tissues under drought. T7-IITJ also improved the germination and seedling growth of Tephrosia purpurea, Triticum aestivum, and Setaria italica under drought and inhibited the growth of two plant pathogenic fungi, Fusarium oxysporum, and Rhizoctonia solani. CONCLUSIONS: P. frigoritolerans T7-IITJ is a potent biofertilizer that regulates plant genes to promote growth and drought tolerance.
Subject(s)
Arabidopsis , Bacillus , Arabidopsis/genetics , Arabidopsis/metabolism , Genes, Plant , Indoleacetic Acids/metabolism , Bacteria , Phosphates/metabolism , Iron/metabolism , Plant Roots/microbiology , DroughtsABSTRACT
Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land's cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.
Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Peptides , Polyketides , Humans , Escherichia coli/genetics , Escherichia coli/metabolism , Tumor Microenvironment , Drug Resistance, Neoplasm , Mutagens/metabolism , Neoplasm Recurrence, Local , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Polyketides/metabolism , LipidsABSTRACT
The Beas River is one of the important rivers of the Indus River system located in Himachal Pradesh, India, that harbors a diverse range of freshwater fish species. The present study employed COI gene to investigate the ichthyofaunal diversity of river Beas. Through the sequencing of 203 specimens from Beas River, we identified 43 species, belonging to 31 genera, 16 families, and 10 orders. To analyze the genetic divergence and phylogeny of identified species, 485 sequences of Indian origin were retrieved from BOLD, resulting in a dataset of 688 sequences. Our findings consistently revealed a hierarchical increase in the mean K2P genetic divergence within species (0.80%), genus (9.06%), and families (15.35%). Automated Barcode Gap discovery, Neighbour Joining, and Bayesian inference consensus tree methodologies were employed to determine the putative species and their phylogeny, successfully delimiting most of the species with only a few exceptions. The results unveiled six species exhibiting high intra-species divergence (> 2%), suggesting the presence of sibling species and falsely identified sequences on online databases. The present study established the first DNA barcoding-based inventory of freshwater fish species in the Beas River providing comprehensive insights into economically exploited endangered and vulnerable species. In order to ensure the sustainable use of aquatic resources in the Beas River, we recommend the implementation of species measures to protect biodiversity and genetic resources.