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BACKGROUND: Higher red blood cell distribution width (RDW) levels are associated with mortality in patients with chronic obstructive pulmonary disease (COPD). However, more convincing evidence is still lacking, and the relationship between hemoglobin-to-red blood cell distribution width ratio (HRR) and mortality in patients with COPD remains unclear. METHODS: This study is a prospective cohort study that includes 3,745 adult patients with COPD from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018 in the United States. COX proportional hazards regression analysis, Kaplan-Meier survival curves and restricted cubic spline models were employed to investigate the association of RDW and HRR levels with mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of RDW and HRR in predicting mortality in patients with COPD. RESULTS: Higher RDW level was positively associated with increased risk of all-cause mortality (HR = 1.16, 95% CI = 1.11-1.21, P < 0.001), cardiovascular disease (CVD) mortality (HR = 1.13, 95% CI = 1.06-1.21, P < 0.001), and chronic lower respiratory disease (CLRD) related mortality (HR = 1.15, 95% CI = 1.05-1.25, P = 0.003) after adjusting for various potential confounders. HRR was inversely associated with all-cause mortality (HR = 0.14, 95% CI = 0.08-0.25, P < 0.001), CVD mortality (HR = 0.12, 95% CI = 0.05-0.31, P < 0.001). HRR has no significant correlation with CLRD-related mortality. The time-dependent ROC curve showed that RDW exhibited area under the curves (AUCs) of the 5- and 10-year survival rates were 0.707 and 0.714 for all-cause mortality and 0.686 and 0.698, respectively, for CVD mortality. HRR yielded AUCs of the 5- and 10-year survival rates were 0.661 and 0.653 for all-cause mortality and 0.654 and 0.66, respectively, for CVD mortality. CONCLUSION: Higher RDW levels were positively associated with an increased risk of mortality in patients with COPD. HRR levels were negatively correlated with the risk of all-cause and CVD mortality. The predictive value of HRR for mortality in these patients is lower than that of RDW.
Subject(s)
Erythrocyte Indices , Hemoglobins , Nutrition Surveys , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/mortality , Male , Female , Middle Aged , Aged , Prospective Studies , United States/epidemiology , Hemoglobins/analysis , ROC Curve , Proportional Hazards Models , Kaplan-Meier Estimate , Predictive Value of TestsABSTRACT
Abscisic acid (ABA) significantly regulates plant growth and development, promoting tuberous root formation in various plants. However, the molecular mechanisms of ABA in the tuberous root development of Pseudostellaria heterophylla are not yet fully understood. This study utilized Illumina sequencing and de novo assembly strategies to obtain a reference transcriptome associated with ABA treatment. Subsequently, integrated transcriptomic and proteomic analyses were used to determine gene expression profiles in P. heterophylla tuberous roots. ABA treatment significantly increases the diameter and shortens the length of tuberous roots. Clustering analysis identified 2,256 differentially expressed genes and 679 differentially abundant proteins regulated by ABA. Gene co-expression and protein interaction networks revealed ABA positively induced 30 vital regulators. Furthermore, we identified and assigned putative functions to transcription factors (PhMYB10, PhbZIP2, PhbZIP, PhSBP) that mediate ABA signaling involved in the regulation of tuberous root development, including those related to cell wall metabolism, cell division, starch synthesis, hormone metabolism. Our findings provide valuable insights into the complex signaling networks of tuberous root development modulated by ABA. It provided potential targets for genetic manipulation to improve the yield and quality of P. heterophylla, which could significantly impact its cultivation and medicinal value.
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Landfill leachate-containing per- and polyfluoroalkyl substances (PFAS) is both an important 'sink' and a 'source' of secondary pollution, posing serious threaten to surrounding environments. To date, the pollution characteristics of PFAS in landfill leachate, and the coexistence and interaction between PFAS and other leachate contaminants, such as dissolved organic matter (DOM) and toxic metals remains unclear. Herein, our results showed that 17 target PFAS, with concentrations ranged from 1804 to 43309 ng/L, were detected in landfill leachates. The main PFAS were short-chain and even-chain substances represented by perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS). Leachate derived DOM is mainly composed of protein-like and humic-like substance, among which the total contribution of protein-like substance is as high as 73.7%. Correlation analysis results showed that the distribution of PFAS was strongly correlated with the substituted functional groups (e.g., carboxyl and hydroxyl) on the aromatic ring of humic-like substance (C2 and E253/E203) and autochthonous metabolism by microbial activities (FI). Furthermore, Mn element showed a significantly strong correlation with PFAS. Both organic and inorganic substances positively correlated with toxic metals. Our findings are helpful to understand the environmental fate of PFAS, and contribute to decision-making regarding DOM, toxic metals, and PFAS management in landfill.
Subject(s)
Fluorocarbons , Humic Substances , Waste Disposal Facilities , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Fluorocarbons/analysis , Humic Substances/analysis , Environmental Monitoring , Metals/analysis , Metals/toxicityABSTRACT
Silver nanoparticles (AgNPs) are known for their antibacterial properties and their ability to promote wound healing. By incorporating silver nanoparticles into medical gauze, the resulting composite material shows promise as an advanced wound dressing. However, clinical applications are hindered by challenges related to the stability of silver nanoparticle loading on the gauze as nanoparticle leaching can compromise antibacterial efficacy. In this study, silver nanoparticles were immobilized onto polydopamine (PDA) submicron particles, which were then used to modify medical gauze. Energy dispersive spectroscopy (EDS) was employed to analyze the elemental distribution on the modified gauze, confirming successful surface modification. The antibacterial properties of the modified gauze were assessed using a laser scanning confocal microscope (CLSM). The results demonstrated a significant reduction in the adhesion rates of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by 99.1% and 63%, respectively, on the PDA-Ag-modified gauze. Optical density (OD) measurements at 590 nm indicated that the modified gauze effectively inhibited biofilm formation, underscoring its potent antimicrobial capabilities. Further antibacterial efficacy was evaluated by diluting and plating co-cultured bacterial solutions with the modified dressing, followed by 24 h incubation and colony counting. The gauze exhibited an antibacterial efficiency of 99.99% against E. coli and 99.8% against S. aureus. Additionally, cell compatibility tests, involving the co-culture of PDA-Ag composites with human cells, demonstrated excellent biocompatibility. These findings suggest that PDA-Ag-modified medical gauze holds significant potential for the treatment of infected wounds, offering a promising solution to improve wound care through enhanced antimicrobial activity and biocompatibility.
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BACKGROUND: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG. METHODS: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale. RESULTS: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2, and NOX individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM2.5 absorbance and NO2 in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly. CONCLUSION: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.
Subject(s)
Air Pollutants , Air Pollution , Environmental Exposure , Genetic Predisposition to Disease , Glaucoma, Open-Angle , Humans , Glaucoma, Open-Angle/genetics , Glaucoma, Open-Angle/epidemiology , Glaucoma, Open-Angle/chemically induced , Air Pollution/statistics & numerical data , Air Pollution/adverse effects , Middle Aged , Air Pollutants/analysis , Female , Male , Prospective Studies , Environmental Exposure/statistics & numerical data , Particulate Matter , Incidence , United Kingdom/epidemiology , AgedABSTRACT
Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.
Subject(s)
Antilymphocyte Serum , Busulfan , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Vidarabine , Humans , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Vidarabine/administration & dosage , Vidarabine/therapeutic use , Male , Middle Aged , Female , Antilymphocyte Serum/administration & dosage , Busulfan/administration & dosage , Busulfan/therapeutic use , Retrospective Studies , Aged , Hematopoietic Stem Cell Transplantation/methods , Adult , Graft vs Host Disease/epidemiology , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/therapy , Hematologic Neoplasms/mortality , Transplantation, Haploidentical/methods , Survival RateABSTRACT
Understanding the intricate regulatory mechanisms underlying the anthocyanin content (AC) in fruits and vegetables is crucial for advanced biotechnological customization. In this study, we generated high-quality haplotype-resolved genome assemblies for two mulberry cultivars: the high-AC 'Zhongsang5801' (ZS5801) and the low-AC 'Zhenzhubai' (ZZB). Additionally, we conducted a comprehensive analysis of genes associated with AC production. Through genome-wide association studies (GWAS) on 112 mulberry fruits, we identified MaVHAG3, which encodes a vacuolar-type H+-ATPase G3 subunit, as a key gene linked to purple pigmentation. To gain deeper insights into the genetic and molecular processes underlying high AC, we compared the genomes of ZS5801 and ZZB, along with fruit transcriptome data across five developmental stages, and quantified the accumulation of metabolic substances. Compared to ZZB, ZS5801 exhibited significantly more differentially expressed genes (DEGs) related to anthocyanin metabolism and higher levels of anthocyanins and flavonoids. Comparative analyses revealed expansions and contractions in the flavonol synthase (FLS) and dihydroflavonol 4-reductase (DFR) genes, resulting in altered carbon flow. Co-expression analysis demonstrated that ZS5801 displayed more significant alterations in genes involved in late-stage AC regulation compared to ZZB, particularly during the phase stage. In summary, our findings provide valuable insights into the regulation of mulberry fruit AC, offering genetic resources to enhance cultivars with higher AC traits.
ABSTRACT
This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P<0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.
Subject(s)
Extracellular Traps , Neutrophils , Peroxidase , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Animals , Neutrophils/drug effects , Neutrophils/cytology , Mice , Rats , Peroxidase/metabolism , Peroxidase/genetics , Tetradecanoylphorbol Acetate/pharmacology , Male , Lipopolysaccharides/pharmacology , Rats, Sprague-Dawley , Histones/metabolism , Histones/genetics , HumansABSTRACT
To measure vibration signals, a low-frequency fiber Bragg grating (FBG) acceleration sensor featuring a flexible hinge with a spring support and symmetric compensation structure has been designed. Based on the mechanical model of the sensor's structure, the expressions for sensitivity and resonant frequency of the sensor are derived. The structural parameters of the sensor are optimized, and a simulation analysis is conducted using ANSYS 19.2 software. According to the results of simulation analysis and size optimization, the sensor prototype is constructed. Subsequently, its amplitude-frequency response, sensitivity, and temperature characteristics are investigated through vibration experiments. The experimental results show that the resonant frequency of the sensor is 73 Hz, the operating frequency range is 0~60 Hz, and the sensitivity measures 24.24 pm/g. This design meets the requirements for measuring vibration signals at low frequencies.
ABSTRACT
Sclerotinia disease is one of the most devastating fungal diseases worldwide, as it reduces the yields of many economically important crops. Pathogen-secreted effectors play crucial roles in infection processes. However, key effectors of Ciboria shiraiana, the pathogen primarily responsible for sclerotinia disease in mulberry (Morus spp.), remain poorly understood. In this study, we identified and functionally characterized the effector Cs02526 in C. shiraiana and found that Cs02526 could induce cell death in a variety of plants. Moreover, Cs02526-induced cell death was mediated by the central immune regulator brassinosteroid insensitive 1-associated receptor kinase 1, dependent on a 67-amino acid fragment. Notably, Cs02526 homologs were widely distributed in hemibiotrophic and necrotrophic phytopathogenic fungi, but the homologs failed to induce cell death in plants. Pretreatment of plants with recombinant Cs02526 protein enhanced resistance against both C. shiraiana and Sclerotinia sclerotiorum. Furthermore, the pathogenicity of C. shiraiana was diminished upon spraying plants with synthetic dsRNA-Cs02526. In conclusion, our findings highlight the cell death-inducing effector Cs02526 as a potential target for future biological control strategies against plant diseases.
Subject(s)
Ascomycota , Cell Death , Plant Diseases , Plant Immunity , Ascomycota/physiology , Ascomycota/pathogenicity , Plant Diseases/microbiology , Plant Diseases/immunology , Fungal Proteins/metabolism , Fungal Proteins/genetics , Morus/microbiology , Morus/geneticsABSTRACT
Mercury is a ubiquitous heavy-metal pollutant and poses serious ecological and human-health risks. There is an ever-growing demand for rapid, sensitive, and selective detection of mercury in natural waters, particularly for regions lacking infrastructure specialized for mercury analysis. Here, we show that a sensor based on multi-emission carbon dots (M-CDs) exhibits ultrahigh sensing selectivity toward Hg(II) in complex environmental matrices, tested in the presence of a range of environmentally relevant metal/metalloid ions as well as natural and artificial ligands, using various real water samples. By incorporating structural features of calcein and folic acid that enable tunable emissions, the M-CDs couple an emission enhancement at 432 nm and a simultaneous reduction at 521 nm, with the intensity ratio linearly related to the Hg(II) concentration up to 1200 µg/L, independent of matrix compositions. The M-CDs have a detection limit of 5.6 µg/L, a response time of 1 min, and a spike recovery of 94 ± 3.7%. The intensified emission is attributed to proton transfer and aggregation-induced emission enhancement, whereas the quenching is due to proton and electron transfer. These findings also have important implications for mercury identification in other complex matrices for routine, screening-level food safety and health management practices.
Subject(s)
Carbon , Mercury , Water Pollutants, Chemical , Mercury/analysis , Carbon/chemistry , Water Pollutants, Chemical/analysis , Fluorescence , Quantum Dots/chemistry , Water/chemistryABSTRACT
Landfills are commonly used for waste disposal in many countries, and pose a significant threat of groundwater contamination. Dissolved organic matter (DOM) plays a crucial role as a carbon and energy source, supporting the growth and activity of microorganisms. However, the changes in the DOM signature and microbial community composition in landfill-affected groundwater and their bidirectional relationships remain inadequately explored. Herein, we showed that DOM originating from more recent landfills mainly comprises microbially produced substances resembling tryptophan and tyrosine. Conversely, DOM originating from older landfills predominantly comprises fulvic-like and humic-like compounds. Leachate leakage increases microbial diversity and richness and facilitates the transfer of foreign bacteria from landfills to groundwater, thereby increasing the vulnerability of the microbial ecosystem in groundwater. Deterministic processes dominated the assembly of the groundwater microbial community, while stochastic processes accounted for an increased proportion of the microbial community in the old landfills. The dominant phyla observed in groundwater were Proteobacteria, Bacteroidota, and Actinobacteriota, and humic-like substances play a crucial role in driving the variation in microbial communities in landfill-affected groundwater. Predictions using PICRUSt2 suggested significant associations between various metabolic pathways and microbial communities, with the Kyoto Encyclopedia of Genes and Genomes pathway "Metabolism" being the most predominant. The findings contribute to advancing our understanding of the transformation of DOM and its interplay with microbial communities and can serve as a scientific reference for decision-making regarding groundwater pollution monitoring and remediation.
Subject(s)
Groundwater , Humic Substances , Water Pollutants, Chemical , Groundwater/microbiology , Groundwater/chemistry , Humic Substances/analysis , Water Pollutants, Chemical/analysis , Waste Disposal Facilities , Microbiota , Bacteria/metabolism , Bacteria/genetics , Bacteria/classificationABSTRACT
The energy loss induced open-circuit voltage (VOC) deficit hampers the rapid development of state-of-the-art organic solar cells (OSCs), therefore, it is extremely urgent to explore effective strategies to address this issue. Herein, a new volatile solid additive 1,4-bis(iodomethyl)cyclohexane (DIMCH) featured with concentrated electrostatic potential distribution is utilized to act as a morphology-directing guest to reduce energy loss in multiple state-of-art blend system, leading to one of highest efficiency (18.8%) at the forefront of reported binary OSCs. Volatile DIMCH decreases radiative/non-radiative recombination induced energy loss (ΔE2/ΔE3) by rationally balancing the crystallinity of donors and acceptors and realizing homogeneous network structure of crystal domain with reduced D-A phase separation during the film formation process and weakens energy disorder and trap density in OSCs. It is believed that this study brings not only a profound understanding of emerging volatile solid additives but also a new hope to further reduce energy loss and improve the performance of OSCs.
ABSTRACT
This study investigated the mechanism of Yuxuebi Tablets(YXB) in the treatment of synovial inflammation in rheumatoid arthritis(RA) based on transcriptomic analysis. Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats, collagen-induced arthritis(CIA) rats(an RA model), and YXB-treated rats. Common diffe-rentially expressed genes(DEGs) were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases. Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes, and GO and KEGG enrichment analyses were performed on the intersecting target genes. Immunohistochemistry was used to assess the protein expression levels of the inflammatory factors interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in rat joint tissues. Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway. A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group. A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes. After intersecting with the DEGs in the YXB treatment group, 204 intersecting target genes were identified, primarily involving biological processes such as immune response, signal transduction, and inflammatory response; cellular components including plasma membrane, extracellular space, and extracellular region; molecular functions like protein binding, identical protein binding, and receptor binding. These target genes were mainly enriched in signaling pathways such as PI3K/Akt, cytokine-cytokine receptor interaction, and Janus kinase/signal transducer and activator of transcription(JAK/STAT). Western blot results showed that YXB at low, medium, and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner. Immunohistochemistry further confirmed these findings, showing that YXB not only suppressed the protein expression levels of the inflammatory factors IL-1ß and TNF-α in the joint synovial tissues of CIA rats, but also inhibited p-Akt protein expression. In conclusion, this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA, with a focus on its role in suppressing the PI3K/Akt signaling pathway.
Subject(s)
Arthritis, Rheumatoid , Proto-Oncogene Proteins c-akt , Rats , Animals , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Synovial Membrane , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Gene Expression Profiling/methodsABSTRACT
Remediation of large and dilute plumes of groundwater contaminated by oxidized pollutants such as chromate is a common and difficult challenge. Herein, we show that in situ formation of FeS nanoparticles (using dissolved Fe(II), S(-II), and natural organic matter as a nucleating template) results in uniform coating of aquifer material to create a regenerable reactive zone that mitigates Cr(VI) migration. Flow-through columns packed with quartz sand are amended first with an Fe2+ solution and then with a HS- solution to form a nano-FeS coating on the sand, which does not hinder permeability. This nano-FeS coating effectively reduces and immobilizes Cr(VI), forming Fe(III)-Cr(III) coprecipitates with negligible detachment from the sand grains. Preconditioning the sand with humic or fulvic acid (used as model natural organic matter (NOM)) further enhances Cr(VI) sequestration, as NOM provides additional binding sites of Fe2+ and mediates both nucleation and growth of FeS nanoparticles, as verified with spectroscopic and microscopic evidence. Reactivity can be easily replenished by repeating the procedures used to form the reactive coating. These findings demonstrate that such enhancement of attenuation capacity can be an effective option to mitigate Cr(VI) plume migration and exposure, particularly when tackling contaminant rebound post source remediation.
Subject(s)
Chromium , Groundwater , Oxidation-Reduction , Water Pollutants, Chemical , Groundwater/chemistry , Chromium/chemistry , Water Pollutants, Chemical/chemistry , Nanoparticles/chemistry , Environmental Restoration and Remediation/methods , Humic Substances , Ferrous Compounds/chemistry , Benzopyrans/chemistryABSTRACT
BACKGROUND: The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. METHODS: We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. RESULTS: The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%-17.7%), 16.3% (95% CI 10.2%-23.6%), 76.6% (95% CI 69.0%-85.1%), and 72.8% (95% CI 65.0%-81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%-32.9%), 14.7% (95% CI 5.3%-28.7%), 71.8% (95% CI 57.6%-89.6%), and 68.4% (95% CI 53.6%-87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25-5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10-4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. CONCLUSIONS: In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Primary Myelofibrosis , Humans , Primary Myelofibrosis/complications , Primary Myelofibrosis/therapy , Retrospective Studies , Transplantation, Homologous , Myelodysplastic Syndromes/therapyABSTRACT
Objectives: This study aimed to characterize the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) in 492 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave. Methods: Data were retrospectively collected from patient charts and the electronic medical record systems at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2022 and January 2023. Results: The median follow-up period of the entire cohort was 62 days. Myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%) constituted the most common underlying disease. Among the 492 patients, 415, 67, and 10 exhibited mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7%. The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. The risk factors for moderate-to-severe COVID-19 included corticosteroid use within 3 months before diagnosis, <6 months interval between allo-HSCT and COVID-19 diagnosis, and antithymocyte globulin use for graft-versus-host disease prophylaxis. Conclusions: During the Omicron wave, patients with allo-HSCT demonstrated a low COVID-19-related mortality rate and high moderate-to-severe and prolonged disease incidence. Prevention in the early posttransplantation period is critical for allo-HSCT recipients receiving corticosteroids.
ABSTRACT
Snakehead vesiculovirus (SHVV) is one of the primary pathogens responsible for viral diseases in the snakehead fish. A TaqMan-based real-time PCR assay was established for the rapid detection and quantification of SHVV in this study. Specific primers and fluorescent probes were designed for phosphoprotein (P) gene, and after optimizing the reaction conditions, the results indicated that the detection limit of this method could reach 37.1 copies, representing a 100-fold increase in detection sensitivity compared to RT-PCR. The specificity testing results revealed that this method exhibited no cross-reactivity with ISKNV, LMBV, RSIV, RGNNV, GCRV, and CyHV-2. Repetition experiments demonstrated that both intra-batch and inter-batch coefficients of variation were not higher than 1.66%. Through in vitro infection experiments monitoring the quantitative changes of SHVV in different tissues, the results indicated that the liver and spleen exhibited the highest viral load at 3 poi. The TaqMan-based real-time PCR method established in this study exhibits high sensitivity, excellent specificity, and strong reproducibility. It can be employed for rapid detection and viral load monitoring of SHVV, thus providing a robust tool for the clinical diagnosis and pathogen research of SHVV.
Subject(s)
Fish Diseases , Iridoviridae , Perciformes , Rhabdoviridae Infections , Animals , Perciformes/genetics , Vesiculovirus/genetics , Real-Time Polymerase Chain Reaction , Fish Diseases/diagnosis , Reproducibility of Results , Iridoviridae/genetics , Sensitivity and SpecificityABSTRACT
BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. RESULTS: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. CONCLUSIONS: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib.
Subject(s)
Dasatinib , Hematopoietic Stem Cell Transplantation , Imatinib Mesylate , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Protein Kinase Inhibitors , Transplantation, Homologous , Humans , Dasatinib/therapeutic use , Dasatinib/adverse effects , Retrospective Studies , Male , Female , Adult , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Middle Aged , Imatinib Mesylate/therapeutic use , Young Adult , Adolescent , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Treatment Outcome , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Graft vs Host Disease/prevention & control , Graft vs Host Disease/etiologyABSTRACT
Cannabis glandular trichomes (GTs) are economically and biotechnologically important structures that have a remarkable morphology and capacity to produce, store, and secrete diverse classes of secondary metabolites. However, our understanding of the developmental changes and the underlying molecular processes involved in cannabis GT development is limited. In this study, we developed Cannabis Glandular Trichome Detection Model (CGTDM), a deep learning-based model capable of differentiating and quantifying three types of cannabis GTs with a high degree of efficiency and accuracy. By profiling at eight different time points, we captured dynamic changes in gene expression, phenotypes, and metabolic processes associated with GT development. By integrating weighted gene co-expression network analysis with CGTDM measurements, we established correlations between phenotypic variations in GT traits and the global transcriptome profiles across the developmental gradient. Notably, we identified a module containing methyl jasmonate (MeJA)-responsive genes that significantly correlated with stalked GT density and cannabinoid content during development, suggesting the existence of a MeJA-mediated GT formation pathway. Our findings were further supported by the successful promotion of GT development in cannabis through exogenous MeJA treatment. Importantly, we have identified CsMYC4 as a key transcription factor that positively regulates GT formation via MeJA signaling in cannabis. These findings provide novel tools for GT detection and counting, as well as valuable information for understanding the molecular regulatory mechanism of GT formation, which has the potential to facilitate the molecular breeding, targeted engineering, informed harvest timing, and manipulation of cannabinoid production.