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1.
Plant Physiol ; 195(3): 2406-2427, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38588053

ABSTRACT

Plants undergo various age-dependent changes in leaf morphology during juvenile to adult vegetative stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a-MdSPL14-MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a-MdSPL14-MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.


Subject(s)
Cytokinins , Gene Expression Regulation, Plant , Malus , Plant Leaves , Plant Proteins , Malus/genetics , Malus/growth & development , Malus/metabolism , Malus/anatomy & histology , Plant Leaves/genetics , Plant Leaves/anatomy & histology , Plant Leaves/growth & development , Plant Leaves/metabolism , Cytokinins/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Oxidoreductases/metabolism , Oxidoreductases/genetics , Signal Transduction
2.
BMC Plant Biol ; 24(1): 445, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38778277

ABSTRACT

BACKGROUND: Acer is a taxonomically intractable and speciose genus that contains over 150 species. It is challenging to distinguish Acer species only by morphological method due to their abundant variations. Plastome and nuclear ribosomal DNA (nrDNA) sequences are recommended as powerful next-generation DNA barcodes for species discrimination. However, their efficacies were still poorly studied. The current study will evaluate the application of plastome and nrDNA in species identification and perform phylogenetic analyses for Acer. RESULT: Based on a collection of 83 individuals representing 55 species (c. 55% of Chinese species) from 13 sections, our barcoding analyses demonstrated that plastomes exhibited the highest (90.47%) species discriminatory power among all plastid DNA markers, such as the standard plastid barcodes matK + rbcL + trnH-psbA (61.90%) and ycf1 (76.19%). And the nrDNA (80.95%) revealed higher species resolution than ITS (71.43%). Acer plastomes show abundant interspecific variations, however, species identification failure may be due to the incomplete lineage sorting (ILS) and chloroplast capture resulting from hybridization. We found that the usage of nrDNA contributed to identifying those species that were unidentified by plastomes, implying its capability to some extent to mitigate the impact of hybridization and ILS on species discrimination. However, combining plastome and nrDNA is not recommended given the cytonuclear conflict caused by potential hybridization. Our phylogenetic analysis covering 19 sections (95% sections of Acer) and 128 species (over 80% species of this genus) revealed pervasive inter- and intra-section cytonuclear discordances, hinting that hybridization has played an important role in the evolution of Acer. CONCLUSION: Plastomes and nrDNA can significantly improve the species resolution in Acer. Our phylogenetic analysis uncovered the scope and depth of cytonuclear conflict in Acer, providing important insights into its evolution.


Subject(s)
Acer , DNA Barcoding, Taxonomic , DNA, Plant , DNA, Ribosomal , Phylogeny , Acer/genetics , DNA Barcoding, Taxonomic/methods , DNA, Ribosomal/genetics , DNA, Plant/genetics , Plastids/genetics , Species Specificity , Cell Nucleus/genetics
3.
Plant Biotechnol J ; 22(1): 116-130, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37752622

ABSTRACT

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/metabolism , Disease Resistance/genetics , Feedback , Arabidopsis/metabolism , Cell Death , Plant Diseases/genetics , Gene Expression Regulation, Plant/genetics
4.
Phys Rev Lett ; 132(19): 191901, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38804936

ABSTRACT

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

5.
BMC Cancer ; 24(1): 799, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965454

ABSTRACT

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.


Subject(s)
Craniopharyngioma , Inflammation Mediators , Leptin , Pituitary Neoplasms , Progression-Free Survival , Humans , Craniopharyngioma/metabolism , Craniopharyngioma/pathology , Craniopharyngioma/mortality , Craniopharyngioma/complications , Female , Male , Adult , Pituitary Neoplasms/mortality , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Pituitary Neoplasms/blood , Middle Aged , Inflammation Mediators/metabolism , Leptin/blood , Leptin/metabolism , Prognosis , Obesity/complications , Obesity/metabolism , Obesity, Morbid/complications , Obesity, Morbid/metabolism , Obesity, Morbid/mortality , Young Adult , Chemokine CXCL1/metabolism , Chemokine CXCL1/blood , Age of Onset , Risk Factors , Clinical Relevance , Interleukin-8
6.
BMC Cancer ; 24(1): 521, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38658858

ABSTRACT

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.


Subject(s)
Craniopharyngioma , Feces , Gastrointestinal Microbiome , Pituitary Neoplasms , Humans , Craniopharyngioma/metabolism , Male , Female , Adult , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/microbiology , Feces/microbiology , Middle Aged , Case-Control Studies , Young Adult , Adolescent , Metabolomics/methods , Metagenomics/methods , Metabolome
7.
Wound Repair Regen ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39169718

ABSTRACT

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

8.
Acta Pharmacol Sin ; 45(1): 98-111, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37726422

ABSTRACT

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.


Subject(s)
Actins , Neointima , Rats , Animals , Becaplermin/pharmacology , Neointima/drug therapy , Neointima/metabolism , Actins/metabolism , Rats, Sprague-Dawley , Sphingosine-1-Phosphate Receptors/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte Colony-Stimulating Factor/pharmacology , Muscle, Smooth, Vascular , Molecular Docking Simulation , Cell Proliferation , Signal Transduction , Cell Movement , Myocytes, Smooth Muscle/metabolism , Cells, Cultured
9.
J Nanobiotechnology ; 22(1): 417, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014353

ABSTRACT

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.


Subject(s)
Gels , Sirolimus , Animals , Rabbits , Sirolimus/pharmacology , Sirolimus/pharmacokinetics , Sirolimus/chemistry , Humans , Gels/chemistry , Cornea/drug effects , Cornea/metabolism , Rats , Male , Polysaccharides, Bacterial/chemistry , Nanoparticles/chemistry , Administration, Ophthalmic , Corneal Neovascularization/drug therapy , Rats, Sprague-Dawley , Viscosity , Drug Delivery Systems , Ophthalmic Solutions/chemistry , Ophthalmic Solutions/pharmacology , Cell Line , Biological Availability
10.
Blood Purif ; : 1-18, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39265561

ABSTRACT

INTRODUCTION: Hypophosphatemia is a common and potentially severe complication of continuous kidney replacement therapy (CKRT), but the evidence on the correlation between hypophosphatemia occurring during CKRT and clinical outcomes remains limited. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to March 1, 2024. All possible studies that examined the following outcomes were included: all-cause mortality, mechanical ventilation, intensive care unit (ICU) stay, and CKRT duration. RESULTS: A total of 8,631 patients from eight cohort studies were included. There was no statistical association between hypophosphatemia during CKRT and all-cause mortality in critically ill patients (OR 0.82, 95% CI 0.57-1.18, P =0.28, I2 = 83%). However, hypophosphatemia was associated with longer duration of mechanical ventilation (WMD 80.30h, 95% CI 31.37-129.22, P =0.001, I2 = 60%). Furthermore, a longer length of ICU stay (WMD 2.76d, 95% CI 2.50-3.02, P <0.00001, I2 = 36%) and CKRT duration (WMD 51.51h, 95% CI 2.69-100.34, P =0.04, I2 = 96%) were observed in patients with hypophosphatemia. CONCLUSIONS: The association between hypophosphatemia and mortality in patients receiving CKRT was insufficient. However, hypophosphatemia during CKRT might be associated with adverse clinical outcomes for critically ill patients.

11.
Chem Biodivers ; 21(6): e202400583, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38590217

ABSTRACT

Plant disease control mainly relies on pesticides. In this study, a series of coumarin derivatives containing hydrazone moiety were designed and synthesized. The synthesized compounds were characterized and used to evaluate the antifungal activity against four pathogens, Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria alternata. The results showed that the inhibition rate of some compounds at 100 µg/mL in 96 hours reached around 70 % against A. alternata, higher than that of the positive control. The corresponding EC50 values were found at around 30 µg/mL. Finally, the compound 3 b was screened out with the lowest EC50 value (19.49 µg/mL). The analysis of SEM and TEM confirmed that the compound 3 b can obviously damage the morphological structure of hyphae, resulting in the depletion of the cells by the destruction of morphological matrix and leakage of contents. RNA sequencing showed that compounds 3 b mainly affected the pentose phosphate pathway, which caused to destroy the layer of mitochondrial structure. Molecular docking showed that compounds 3 b fitted the binding pocket of yeast transketolase and interacted with lysine at the hydrazone structure. Our results suggested that the introduction of hydrazone was an effective strategy for the design of novel bioactive compounds.


Subject(s)
Alternaria , Antifungal Agents , Botrytis , Coumarins , Fusarium , Hydrazones , Microbial Sensitivity Tests , Molecular Docking Simulation , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Coumarins/chemistry , Coumarins/pharmacology , Coumarins/chemical synthesis , Alternaria/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Fusarium/drug effects , Structure-Activity Relationship , Botrytis/drug effects , Molecular Structure , Dose-Response Relationship, Drug
12.
Chem Biodivers ; 21(5): e202400311, 2024 May.
Article in English | MEDLINE | ID: mdl-38494946

ABSTRACT

Phytopathogenic fungi is the most devastating reason for the decrease of the agricultural production and food safety. To develop new fungicidal agents for resistance concerning, a novel series of aminocoumarin derivatives were synthesized and their fungicidal activity were investigated both in vitro and in vivo. Transmission electron microscope (TEM), scanning electron microscope (SEM), RNA-Seq, 3D-QSAR and molecular docking were applied to reveal the underlying anti-fungal mechanisms. Most of the compounds exhibited significant fungicidal activity. Notably, compound 10c had a more extensive fungicidal effect than positive control. TEM indicated that compound 10c could cause abnormal morphology of cell walls, vacuoles and release of cellular contents. Transcriptional analysis data indicated that 895 and 653 out of 1548 differential expressed genes (DEGs) were up-regulated and down-regulated respectively. The Go and KEGG enrichment indicated that the coumarin derivatives could induce significant changes of succinate dehydrogenase (SDH), Acetyl-coenzyme A synthetase (ACCA) and pyruvate dehydrogenase (PDH) genes, which contributed to the disorders of glucolipid metabolism and the dysfunction of mitochondrial. The results demonstrated that aminocoumarins with schiff-base as core moieties could be the promising lead compounds for the discovery of novel fungicides.


Subject(s)
Coumarins , Drug Design , Coumarins/pharmacology , Coumarins/chemistry , Coumarins/chemical synthesis , Structure-Activity Relationship , Molecular Docking Simulation , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Molecular Structure , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Quantitative Structure-Activity Relationship , Botrytis/drug effects
13.
Chem Biodivers ; : e202401390, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39169237

ABSTRACT

Structural modification is an effective way to improve the antifungal activity of natural products and has been widely used in the development of novel fungicides. In this work, a series of aminocoumarin-based Schiff bases were synthesized and characterized by 1H NMR, 13C NMR and HR-MS spectra. The in vitro inhibition activity of all compounds was tested against four phytopathogenic fungi (Alternaria solani, Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata) using the mycelial growth rate method. The results showed that most of the target compounds exhibited significant antifungal activities. In particular, compounds 5b, 5c, 5d, 5h, 5n, 7c, 7n, and 7p exhibited more effective antifungal activity than commercially available fungicides, chlorothalonil and azoxystrobin. The structure-activity relationship revealed that the electron-withdrawing groups with more electronegativity introduced at the C-3 position were effective in improving the inhibitory activity and that halogenated benzaldehydes would be necessary in the preparation of Schiff bases. The compound 5n against Fusarium oxysporum (EC50=8.73 µg/mL) and the compound 7p against Alternaria alternata (EC50=26.25 µg/mL) were much better than the positive controls. Therefore, compounds 5n and 7p could serve as promising lead compounds for the development of novel broad-spectrum fungicides, which could be useful for applications in the agriculture industry.

14.
Foodborne Pathog Dis ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39110468

ABSTRACT

Protein-based detection methods, enzyme-linked immunosorbent assays (ELISAs) and lateral flow strips, have been widely used for rapid, specific, and sensitive detection of genetically modified organisms (GMOs). However, the traditional ELISA method for the quantitative detection of GMOs has certain limitations. Herein, a quantum dot (QD)-based fluorescence-linked immunosorbent assay was developed using QDs as fluorescent markers for the detection of glyphosate-resistant protein (CP4-EPSPS) in the MON89788 soybean. The end-point fluorescent detection system was carried out using QDs conjugated with a goat anti-rabbit secondary antibody. Compared with the conventional sandwich ELISA method, the newly developed fluorescence-linked immunosorbent assay was highly sensitive and accurate for detecting the CP4-EPSPS protein. The quantified linearity was achieved in the range of 0.05-5% (w/w) for the MON89788 soybean sample. The recovery of protein extracted from mixed MON89788 soybean samples ranged from 87.67% to 116.83%. The limits of detection and limits of quantification were 0.7101 and 2.152 pg/mL, respectively. All of the results indicated that the QD-based fluorescence-linked immunosorbent assay was a highly specific and sensitive method for monitoring the CP4-EPSPS protein in GMOs.

15.
Int J Mol Sci ; 25(17)2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39273581

ABSTRACT

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Esophageal Neoplasms , Molecular Docking Simulation , Pyridones , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Pyridones/pharmacology , Pyridones/chemistry , Pyridones/chemical synthesis , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Cell Proliferation/drug effects , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Apoptosis/drug effects
16.
Molecules ; 29(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38999117

ABSTRACT

Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.


Subject(s)
Anti-Bacterial Agents , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Propionibacteriaceae/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Proteomics/methods , Acrolein/analogs & derivatives , Acrolein/pharmacology , Acrolein/chemistry , Metabolomics/methods
17.
Molecules ; 29(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38731534

ABSTRACT

Two unreported heteropolysaccharides, denoted as YCJP-1 and YCJP-2, were isolated from the herbs of Chloranthus japonicus. YCJP-1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475-228,443 Da range. YCJP-2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP-1 and YCJP-2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP-1, and YCJP-2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP-1, and YCJP-2. Moreover, YCJP-2 demonstrated superior anti-gastric cancer effects compared to YCJP-1. This could potentially be attributed to YCJP-2's higher glucose content and narrower molecular weight distribution.


Subject(s)
Cell Proliferation , Polysaccharides , Stomach Neoplasms , Humans , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Molecular Weight , Caryophyllaceae/chemistry
18.
Indian J Microbiol ; 64(3): 1035-1043, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39282164

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

19.
Plant J ; 110(1): 166-178, 2022 04.
Article in English | MEDLINE | ID: mdl-34997660

ABSTRACT

Many rice microRNAs have been identified as fine-tuning factors in the regulation of agronomic traits and immunity. Among them, Osa-miR535 targets SQUAMOSA promoter binding protein-like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa-miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa-miR535 significantly decreased the accumulation of the fusion protein SPL4TBS -YFP that contains the target site of Osa-miR535 in OsSPL4. Consistently, Osa-miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3' untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense-relative genes and up-accumulated H2 O2 . By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole-3-acetic acid-amido synthetase, and promotes its expression. Together, these data indicate that Os-miR535 targets OsSPL4 and OsSPL4-GH3.2, which may parallel the OsSPL14-WRKY45 module in rice blast disease resistance.


Subject(s)
Magnaporthe , Oryza , Carrier Proteins/metabolism , Disease Resistance/genetics , Gene Expression Regulation, Plant , Magnaporthe/metabolism , Oryza/metabolism , Plant Diseases , Plant Proteins/genetics , Plant Proteins/metabolism
20.
Ecol Lett ; 26(11): 1898-1910, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37776563

ABSTRACT

Metabolomics provides an unprecedented window into diverse plant secondary metabolites that represent a potentially critical niche dimension in tropical forests underlying species coexistence. Here, we used untargeted metabolomics to evaluate chemical composition of 358 tree species and its relationship with phylogeny and variation in light environment, soil nutrients, and insect herbivore leaf damage in a tropical rainforest plot. We report no phylogenetic signal in most compound classes, indicating rapid diversification in tree metabolomes. We found that locally co-occurring species were more chemically dissimilar than random and that local chemical dispersion and metabolite diversity were associated with lower herbivory, especially that of specialist insect herbivores. Our results highlight the role of secondary metabolites in mediating plant-herbivore interactions and their potential to facilitate niche differentiation in a manner that contributes to species coexistence. Furthermore, our findings suggest that specialist herbivore pressure is an important mechanism promoting phytochemical diversity in tropical forests.


Subject(s)
Herbivory , Rainforest , Animals , Forests , Plant Leaves , Phylogeny , Insecta
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