-
Scientific Reports Jun 2024Flavonoids are crucial secondary metabolites that possess the ability to mitigate UV damage and withstand both biotic and abiotic stresses. Therefore, it is of immense...
Flavonoids are crucial secondary metabolites that possess the ability to mitigate UV damage and withstand both biotic and abiotic stresses. Therefore, it is of immense significance to investigate the flavonoid content as a pivotal indicator for a comprehensive assessment of chestnut's drought tolerance. This study aimed to determine the flavonoid content and drought tolerance-related physiological and biochemical indices of six chestnut varieties (clones) grafted trees-Qianxi 42 (QX42), Qinglong 45 (QL45), Yanshanzaofeng (YSZF), Yanzi (YZ), Yanqiu (YQ), and Yanlong (YL)-under natural drought stress. The results were used to comprehensively analyze the drought tolerance ability of these varieties. The study revealed that the ranking of drought tolerance indices in terms of their ability to reflect drought tolerance was as follows: superoxide (oxide) dismutase (SOD) activity, ascorbate peroxidase (APX) activity, flavone content, catalase (CAT) activity, proline (PRO) content, soluble sugar content, peroxidase (POD) activity, betaine content, flavonol content, hydrogen peroxide (HO) content, soluble protein content, superoxide ion (OFR) content, superoxide (ion OFR) production rate, malondialdehyde (MDA) content, chlorophyll content. Through principal component analysis, the contents of flavonoids and flavonols can be used as indicators for comprehensive evaluation of drought tolerance of chestnut. The comprehensive evaluation order of drought tolerance of grafted trees of 6 chestnut varieties (Clones) was: QL45 > QX42 > YQ > YZ > YSZF > YL.
Topics: Flavonoids; Droughts; Stress, Physiological; Malondialdehyde; Superoxide Dismutase; Proline; Chlorophyll; Hydrogen Peroxide; Fagaceae; Adaptation, Physiological; Catalase; Ascorbate Peroxidases; Drought Resistance; East Asian People
PubMed: 38914646
DOI: 10.1038/s41598-024-65479-2 -
Scientific Reports Jun 2024Understanding the nitrogen isotopic variations of individual amino acids (AAs) is essential for utilizing the nitrogen isotope values of individual amino acids (δN-AA)...
Understanding the nitrogen isotopic variations of individual amino acids (AAs) is essential for utilizing the nitrogen isotope values of individual amino acids (δN-AA) as source indicators to identify proteinaceous matter originating from biomass combustion processes. However, the nitrogen isotope effects (ε) associated with the degradation of individual amino acids during combustion processes have not been previously explored. In this study, we measured the nitrogen isotope values of residual free amino acids -following a series of controlled combustion experiments at temperatures of 160-240 °C and durations of 2 min to 8 h, as described in Part 1. δN values of proline, aspartate, alanine, valine, glycine, leucine, and isoleucine are more positive than their initial δN values after prolonged combustion. Variations in δN values of the most AAs conform to the Rayleigh fractionation during combustion and their nitrogen isotope effects (ε) are greatly impacted by their respective combustion degradation pathways. This is the first time the ε values associated with the degradation pathways of AAs during combustion have been characterized. Only the ε values associated with Pathway 1 (dehydration to form dipeptide) and 2 (simultaneous deamination and decarboxylation) are found to be significant and temperature-dependent, ranging from + 2.9 to 6.4‰ and + 0.9‰ to + 3.8‰, respectively. Conversely, ε values associated with other pathways are minor. This improves the current understanding on the degradation mechanisms of protein nitrogen during biomass burning.
Topics: Amino Acids; Nitrogen Isotopes; Kinetics; Biomass; Temperature
PubMed: 38914616
DOI: 10.1038/s41598-024-65544-w -
PLoS Biology Jun 2024In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of...
In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-β nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-β ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-β type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-β ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-β, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.
PubMed: 38913712
DOI: 10.1371/journal.pbio.3002701 -
Frontiers in Public Health 2024The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools.
BACKGROUND
The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools.
METHODOLOGY
This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood.
RESULTS
Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions.
CONCLUSION
This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.
Topics: Humans; Saliva; HIV Infections; Biomarkers; Male; Metabolome; Adult; Female; Antiretroviral Therapy, Highly Active; Middle Aged; Chromatography, Liquid; Metabolomics; Tandem Mass Spectrometry; Early Diagnosis; CD4 Lymphocyte Count
PubMed: 38912274
DOI: 10.3389/fpubh.2024.1400332 -
Frontiers in Cellular and Infection... 2024Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic...
INTRODUCTION
Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.
METHODS
This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.
RESULTS
Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against , with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of . Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.
DISCUSSION
In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.
Topics: Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Metal-Organic Frameworks; Drugs, Chinese Herbal; Staphylococcus aureus; Drug Synergism; Powders; Humans; Chromatography, Liquid
PubMed: 38912207
DOI: 10.3389/fcimb.2024.1376312 -
Frontiers in Plant Science 2024Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when...
Metabolomics and physio-chemical analyses of mulberry plants leaves response to manganese deficiency and toxicity reveal key metabolites and their pathways in manganese tolerance.
INTRODUCTION
Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when applied in excess. is an economically significant plant, capable of adapting to a range of environmental conditions and possessing the potential for phytoremediation of contaminated soil by HMs. The mechanism by which tolerates Mn stresses remains obscure.
METHODS
In this study, Mn concentrations comprising sufficiency (0.15 mM), higher regimes (1.5 mM and 3 mM), and deficiency (0 mM and 0.03 mM), were applied to in pot treatment for 21 days to understand Mn tolerance. Mn stress effects on the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO concentration (Ci), chlorophyll content, plant morphological traits, enzymatic and non-enzymatic parameters were analyzed as well as metabolome signatures via non-targeted LC-MS technique.
RESULTS
Mn deficiency and toxicity decrease plant biomass, Pn, Ci, Gs, Tr, and chlorophyll content. Mn stresses induced a decline in the activities of catalase (CAT) and superoxide dismutase (SOD), while peroxidase (POD) activity, and leaf Mn content, increased. Soluble sugars, soluble proteins, malondialdehyde (MDA) and proline exhibited an elevation in Mn deficiency and toxicity concentrations. Metabolomic analysis indicates that Mn concentrations induced 1031 differentially expressed metabolites (DEMs), particularly amino acids, lipids, carbohydrates, benzene and derivatives and secondary metabolites. The DEMs are significantly enriched in alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, pantothenate and CoA biosynthesis, pentose phosphate pathway, carbon metabolism, etc.
DISCUSSION AND CONCLUSION
The upregulation of Galactinol, Myo-inositol, Jasmonic acid, L-aspartic acid, Coproporphyrin I, Trigonelline, Pantothenol, and Pantothenate and their significance in the metabolic pathways makes them Mn stress tolerance metabolites in . Our findings reveal the fundamental understanding of DEMs in 's response to Mn nutrition and the metabolic mechanisms involved, which may hold potential significance for the advancement of genetic improvement initiatives and phytoremediation programs.
PubMed: 38911982
DOI: 10.3389/fpls.2024.1349456 -
Signal Transduction and Targeted Therapy Jun 2024Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment...
Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment (TME) in pancreatic cancer, distinguished by fibrosis and the existence of cancer-associated fibroblasts (CAFs), exerts a pivotal influence on both tumor advancement and resistance to therapy. Recent advancements in the field of engineered extracellular vesicles (EVs) offer novel avenues for targeted therapy in pancreatic cancer. This study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic cancer. EVs obtained from bone marrow mesenchymal stem cells (BMSCs) were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone (PFD) and subjected to surface modification with integrin α5-targeting peptides (named IEVs-PFD/138) to reprogram CAFs and suppress their pro-tumorigenic effects. Integrin α5-targeting peptide modification enhanced the CAF-targeting ability of EVs. miR-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex, inhibiting TGF-β signaling pathway activation. In addition, miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 complex. The combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of CAFs. Preclinical experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising results. In particular, IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME, which resulted in decreased tumor pressure, enhanced gemcitabine perfusion, tumor hypoxia amelioration, and greater sensitivity of cancer cells to chemotherapy. Thus, the strategy developed in this study can improve chemotherapy outcomes. Utilizing IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.
Topics: Pancreatic Neoplasms; Extracellular Vesicles; Humans; Cancer-Associated Fibroblasts; Mice; MicroRNAs; Animals; Tumor Microenvironment; Cellular Reprogramming; Cell Line, Tumor; Mesenchymal Stem Cells; Neoplasm Proteins; Gemcitabine
PubMed: 38910148
DOI: 10.1038/s41392-024-01872-7 -
BMC Plant Biology Jun 2024Drought stress poses a significant threat to agricultural productivity, especially in areas susceptible to water scarcity. Sunflower (Helianthus annuus L.) is a widely...
Mitigation of drought-induced stress in sunflower (Helianthus annuus L.) via foliar application of Jasmonic acid through the augmentation of growth, physiological, and biochemical attributes.
Drought stress poses a significant threat to agricultural productivity, especially in areas susceptible to water scarcity. Sunflower (Helianthus annuus L.) is a widely cultivated oilseed crop with considerable potential globally. Jasmonic acid, a plant growth regulator, plays a crucial role in alleviating the adverse impacts of drought stress on the morphological, biochemical, and physiological characteristics of crops. Experimental detail includes sunflower varieties (Armani Gold, KQS-HSF-1, Parsun, and ESFH-3391), four drought stress levels (0, 25%, 50%, and 75% drought stress), and three levels (0, 40ppm, 80ppm) of jasmonic acid. The 0% drought stress and 0ppm jasmonic acid were considered as control treatments. The experimental design was a completely randomized design with three replicates. Drought stress significantly reduced the growth in all varieties. However, the exogenous application of jasmonic acid at concentrations of 40ppm and 80ppm enhanced growth parameters, shoot and root length (1.93%, 19%), shoot and root fresh weight (18.5%, 25%), chlorophyll content (36%), photosynthetic rate (22%), transpiration rate (40%), WUE (20%), MDA (6.5%), Phenolics (19%), hydrogen peroxide (7%) proline (28%) and glycine betaine (15-30%) under water-stressed conditions, which was closely linked to the increase in stomatal activity stimulated by jasmonic acid. Furthermore, JA 80 ppm was found to be the most appropriate dose to reduce the effect of water stress in all sunflower varieties. It was concluded that the foliar application of JA has the potential to enhance drought tolerance by improving the morphological, biochemical, and physiological of sunflower.
Topics: Oxylipins; Cyclopentanes; Helianthus; Droughts; Plant Growth Regulators; Stress, Physiological; Plant Leaves; Photosynthesis; Chlorophyll
PubMed: 38907232
DOI: 10.1186/s12870-024-05273-4 -
Ecotoxicology and Environmental Safety Jun 2024Copper (Cu) is a necessary mineral nutrient for plant growth and development and is involved in several morphological, physiological, and biochemical processes; however,...
Integrated physiological, biochemical, and transcriptomic analyses of Bruguiera gymnorhiza leaves under long-term copper stress: Stomatal size, wax crystals and composition.
Copper (Cu) is a necessary mineral nutrient for plant growth and development and is involved in several morphological, physiological, and biochemical processes; however, high concentrations of Cu can negatively impact these processes. The role of stomata in responding to various biotic and abiotic stimuli has not been studied in Bruguiera gymnorhiza, particularly in terms of their coordinated interactions at the molecular, physiological, and biochemical levels. Moreover, numerous plants employ strategies such as the presence of thick waxy cuticles on their leaf epidermis and the closing of stomata to reduce water loss. Thus, this study investigates the accumulation of Cu in B. gymnorhiza and its effect on leaf morphology and the molecular response under different Cu treatments (0, 200, and 400 mg L⁻¹, Cu0, Cu200, and Cu400, respectively) during a two years stress period. The results show that Cu stress affected accumulation and transport, increased the activities of peroxidase and ascorbate peroxidase, concentrations of soluble sugar, proline, and HO, and decreased the activity of catalase and content of malondialdehyde. Also, Cu-induced stress decreased the uptake of phosphorus and nitrogen and inhibited plant photosynthesis, which consequently led to reduced plant growth. Scanning electron microscopy combined with gas chromatography-mass spectrometry showed that B. gymnorhiza leaves had higher wax crystals and compositions under increased Cu stress, which forced the leaf's stomata to be closed. Also, the contents of alkanes, alcohols, primary alcohol levels (C26:0, C28:0, C30:0, and C32:0), n-Alkanes (C29 and C30), and other wax loads were significantly higher, while fatty acid (C12, C16, and C18) was lower in Cu200 and Cu400 compared to Cu0. Furthermore, the transcriptomic analyses revealed 1240 (771 up- and 469 downregulated), 1000 (723 up- and 277 down-regulated), and 1476 (808 up- and 668 downregulated) differentially expressed genes in Cu0 vs Cu200, Cu0 vs Cu400, and Cu200 vs Cu400, respectively. RNA-seq analyses showed that Cu mainly affected eight pathways, including photosynthesis, cutin, suberin, and wax biosynthesis. This study provides a reference for understanding mangrove response to heavy metal stress and developing novel management practices.
PubMed: 38905937
DOI: 10.1016/j.ecoenv.2024.116609 -
Frontiers in Microbiology 2024The arginine transporter Can1 is a multifunctional protein of the conventional yeast . Apart from facilitating arginine uptake, Can1 plays a pivotal role in regulating...
The arginine transporter Can1 is a multifunctional protein of the conventional yeast . Apart from facilitating arginine uptake, Can1 plays a pivotal role in regulating proline metabolism and maintaining cellular redox balance. Here, we report a novel function of Can1 in the control of yeast biofilm formation. First, the gene knockout strain displayed a significant growth delay compared to the wild-type strain. Our genetic screening revealed that the slow growth of the knockout strain is rescued by a functional deficiency of the gene, which encodes the master transcription factor associated with biofilm formation, indicating that Can1 is involved in biofilm formation. Intriguingly, the knockout strain promoted the Flo11-dependent aggregation, leading to higher biofilm formation. Furthermore, the knockout strain of the pathogenic yeast exhibited slower growth and higher biofilm formation, similar to . More importantly, the gene knockout strain showed severe toxicity to macrophage-like cells and nematodes. The present results could help to elucidate both the molecular mechanism underlying yeast biofilm formation and the role it plays. Future investigations may offer insights that contribute to development of antibiofilm agents.
PubMed: 38903792
DOI: 10.3389/fmicb.2024.1419530