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Instability is a key challenge for current pH sensors in practical applications, especially in aquatic environments with high biomass and redox substances. Herein, we present a novel approach that uses a highly stable IrOx sensing layer enveloped in a composite film of SPEEK doped with a silicon-stabilized ionic liquid (SP-IrOx). This design mitigates drift due to sensitive layer variations and minimizes interference from complex external conditions. After exhibiting robustness under moderately reducing conditions caused by S2-, I-, and ascorbic acid, the SP-IrOx sensor's efficacy was validated through real-time pH measurements in demanding aquatic settings. These included laboratory algal culture medium, sediment substrates, and mussel aquaculture areas. The sensor sustained accuracy and stability over extended periods of 6-8 days when compared to calibrated commercial electrodes. The deviations from reference samples were minimal, with a variance of no more than 0.03 pH units in mussel aquaculture areas (n = 17) and 0.07 pH units in an algal culture medium (n = 37). As a potentiometric, this solid-state electrode features a compact structure and low energy consumption, making it an economical and low-maintenance solution for precise pH monitoring in diverse challenging environments with high biomass and turbidity.
Subject(s)
Biomass , Hydrogen-Ion Concentration , Electrodes , Animals , Aquaculture , Bivalvia/chemistryABSTRACT
The effective treatment of chronic wounds represents a critical global medical challenge demanding urgent attention. Persistent inflammation, driven by an excess of reactive oxygen radicals, sets in motion a detrimental cycle leading to chronic wounds and impeding the natural healing process. This study develops a sprayable wound dressing by covalently grafting amino fullerene to carboxymethylated curdlan (CMC-C). This novel dressing exhibits excellent biocompatibility, antioxidant, and reactive oxygen species scavenging properties. Furthermore, it demonstrates a targeted affinity for HEK-a cells, efficiently reducing the inflammatory response while promoting cell proliferation and migration in vitro. Moreover, the animal experiment investigations reveal that CMC-C significantly accelerates chronic wounds healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. These results demonstrate the potential of the sprayable dressing (CMC-C) in curing the healing of chronic wounds through the modulation of the inflammatory microenvironment. Overall, the sprayable hydrogel dressing based on water-soluble derivative of fullerene and curdlan emerges as a potential approach for clinical applications in the treatment of chronic wounds.
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There is currently increasing pressure on agriculture to simultaneously remediate soil and ensure safe agricultural production. In this study, we investigate the potential of a novel combination of biochar and plant growth-promoting bacteria (PGPB) as a promising approach. Two types of biochar, corn stover and rice husk-derived, were used in combination with a PGPB strain, Bacillus sp. PGP5, to remediate Cd and Pb co-contaminated soil and enhance lettuce performance. The contaminated soil was pre-incubated with biochar prior to PGP5 inoculation. The combined application of biochar and PGPB reduced the diethylenetriaminepentaacetic acid (DTPA) -extractable Cd and Pb concentrations in the soil by 46.45%-55.96% and 42.08%-44.83%, respectively. Additionally, this combined application increased lettuce yield by 23.37%-65.39% and decreased Cd and Pb concentrations in the edible parts of the lettuce by 57.39%-68.04% and 13.57%-32.50%. The combined application showed a better promotion on lettuce growth by facilitating chlorophyll synthesis and reducing oxidative stress. These demonstrated a synergistic effect between biochar and PGPB. Furthermore, our study elucidated the specific role of the biochar-PGPB combination in soil microbial communities. Biochar application promoted the survival of PGP5 in the soil. The impact of biochar or PGPB on microbial communities was found to be most significant in the early stage, while the development of plants had a greater influence on rhizosphere microbial communities in later stage. Plants showed a tendency to recruit plant-associated microbes, such as Cyanobacteria, to facilitate growth processes. Notably, the combined application of biochar and PGPB expedited the assembly of microbial communities, enabling them more closely with the rhizosphere microbial communities in late stage of plant development and thus enhancing their effects on promoting plant growth. This study highlights the "accelerating" advantage of the biochar-PGPB combination in the assembly of rhizosphere microbiomes and offers a new strategy for simultaneous soil remediation and safe agricultural production.
Subject(s)
Charcoal , Lactuca , Soil Microbiology , Soil Pollutants , Soil , Charcoal/chemistry , Soil Pollutants/metabolism , Lactuca/growth & development , Soil/chemistry , Bacillus/metabolism , Vegetables/growth & development , Lead/metabolism , Cadmium/analysis , Cadmium/metabolism , Biodegradation, Environmental , Environmental Restoration and Remediation/methods , Agriculture/methodsABSTRACT
The application of long-lived phosphorescence probes in time-resolved luminescence imaging is limited by their low quantum yield in aqueous solutions. However, sensitization of thermally activated delayed fluorescence (TADF) materials can compensate for this limitation while addressing the issue of insufficient proportion of their own long lifetime. In this study, we utilized the characteristics of phosphorescence and TADF materials simultaneously by doping the receptor iridium complex PMD-Ir into the donor TADF polymer PCzDP-20 through donor-receptor doping method, and successfully prepared highly efficient red phosphorescent nanoparticles. The quantum yield of the nanoparticles obtained by this method reaches up to 30%, and the luminescence lifetime can reach several thousand nanoseconds. Additionally, due to the low concentration doping of PMD-Ir, the risk of transition metal toxicity is greatly reduced. Furthermore, we used non-covalent modification with amphiphilic cell-penetrating peptides (CPPs) to increase the cell membrane permeability of the nanoparticles. The CPPs modified nanoparticles achieve in vivo confocal imaging of zebrafish and intracellular time-resolved imaging by its significantly improved bioimaging capabilities. The functional nanoparticles designing method fully utilizes the characteristics of PMD-Ir, PCzDP-20, and CPPs, solving the problems of low quantum yield and poor membrane permeability of Ir-complex nanoparticles. This will greatly promote the development of time-resolved luminescence imaging.
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Background: Radiation stimulates the secretion of tumor stroma and induces resistance, recurrence, and metastasis of stromal-vascular tumors during radiotherapy. The proliferation and activation of tumor-associated fibroblasts (TAFs) are important reasons for the production of tumor stroma. Telmisartan (Tel) can inhibit the proliferation and activation of TAFs (resting TAFs), which may promote radiosensitization. However, Tel has a poor water solubility. Methods: In this study, self-assembled telmisartan nanoparticles (Tel NPs) were prepared by aqueous solvent diffusion method to solve the insoluble problem of Tel and achieve high drug loading of Tel. Then, erythrocyte membrane (ECM) obtained by hypotonic lysis was coated on the surface of Tel NPs (ECM/Tel) for the achievement of in vivo long circulation and tumor targeting. Immunofluorescence staining, western blot and other biological techniques were used to investigate the effect of ECM/Tel on TAFs activation inhibition (resting effect) and mechanisms involved. The multicellular spheroids (MCSs) model and mouse breast cancer cells (4T1) were constructed to investigate the effect of ECM/Tel on reducing stroma secretion, alleviating hypoxia, and the corresponding promoting radiosensitization effect in vitro. A mouse orthotopic 4T1 breast cancer model was constructed to investigate the radiosensitizing effect of ECM/Tel on inhibiting breast cancer growth and lung metastasis of breast cancer. Results: ECM/Tel showed good physiological stability and tumor-targeting ability. ECM/Tel could rest TAFs and reduce stroma secretion, alleviate hypoxia, and enhance penetration in tumor microenvironment. In addition, ECM/Tel arrested the cell cycle of 4T1 cells to the radiosensitive G2/M phase. In mouse orthotopic 4T1 breast cancer model, ECM/Tel played a superior role in radiosensitization and significantly inhibited lung metastasis of breast cancer. Conclusion: ECM/Tel showed synergistical radiosensitization effect on both the tumor microenvironment and tumor cells, which is a promising radiosensitizer in the radiotherapy of stroma-vascular tumors.
Subject(s)
Lung Neoplasms , Vascular Neoplasms , Mice , Animals , Telmisartan/pharmacology , Telmisartan/therapeutic use , Erythrocyte Membrane , Lung Neoplasms/drug therapy , Radiation Tolerance , Hypoxia , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.
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Multiple myeloma (MM) is a malignant plasma cell disease. The activity of PIK3CG (PI3K catalytic subunit γ) is regulated directly by G-protein-coupled receptor and has been confirmed to be highly expressed in MM cells. This study aimed to determine the effect of pharmacological inhibition of PIK3CG on MM. We found that different concentrations of the PIK3CG inhibitor AS-605240 could suppress the growth of MM cell lines and the expression of c-Myc. The combination of PIK3CG inhibitor and the chemotherapy Melphalan could effectively inhibit the proliferation and migration of MM cells, promote the cell apoptosis, and decrease the ratio of Bcl-2/Bax and the expression of vimentin. The expression of proto-oncogene c-Myc was decreased and the sensitivity of cells to chemotherapeutic drugs was enhanced. Collectively, PIK3CG regulates growth of MM via c-Myc pathway, thus emerging as a promising molecular targeted therapy.
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Background: Cardiomyocyte ischemia and hypoxia are important causes of oxidative stress damage and cardiomyocyte apoptosis in coronary heart disease (CHD). Epidemiological investigation has shown that eating more plant-based foods, such as vegetables and fruits, may significantly decrease the risk of CHD. As natural antioxidants, botanicals have fewer toxic side effects than chemical drugs and have great potential for development. Procyanidin B2 (PB2) is composed of flavan-3-ol and epicatechin and has been reported to have antioxidant and anti-inflammatory effects. However, whether PB2 exerts protective effects on hypoxic cardiomyocytes has remained unclear. This study aimed to explore the protective effect of PB2 against cardiomyocyte hypoxia and to provide new treatment strategies and ideas for myocardial ischemia and hypoxia in CHD. Methods and results: A hypoxic cardiomyocyte model was constructed, and a CCK-8 assay proved that PB2 had a protective effect on cardiomyocytes in a hypoxic environment. DCFH fluorescence staining, DHE staining, and BODIPY lipid oxidation assessment revealed that PB2 reduced the oxidative stress levels of cardiomyocytes under hypoxic conditions. TUNEL staining, Annexin V/PI fluorescence flow cytometry, and Western blot analysis of the expression of the apoptosis marker protein cleaved caspase-3 confirmed that PB2 reduced cardiomyocyte apoptosis under hypoxic conditions. JC-1 staining indicated that PB2 reduced the mitochondrial membrane potential of cardiomyocytes under hypoxia. In addition, transcriptomic analysis proved that the expression of 158 genes in cardiomyocytes was significantly changed after PB2 was added during hypoxia, of which 53 genes were upregulated and 105 genes were downregulated. GO enrichment analysis demonstrated that the activity of cytokines, extracellular matrix proteins and other molecules was changed significantly in the biological process category. KEGG enrichment analysis showed that the IL-17 signaling pathway and JAK-STAT signaling pathway underwent significant changes. We also performed metabolomic analysis and found that the levels of 51 metabolites were significantly changed after the addition of PB2 to cardiomyocytes during hypoxia. Among them, 39 metabolites exhibited increased levels, while 12 metabolites exhibited decreased levels. KEGG enrichment analysis showed that cysteine and methionine metabolism, arginine and proline metabolism and other metabolic pathways underwent remarkable changes. Conclusion: This study proves that PB2 can reduce the oxidative stress and apoptosis of cardiomyocytes during hypoxia to play a protective role. Transcriptomic and metabolomic analyses preliminarily revealed signaling pathways and metabolic pathways that are related to its protective mechanism. These findings lay a foundation for further research on the role of PB2 in the treatment of CHD and provide new ideas and new perspectives for research on PB2 in the treatment of other diseases.
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Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (â¼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.
Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Humans , Male , Middle Aged , Aged , Bradycardia/therapy , Bundle-Branch Block/therapy , Heart Conduction System , Electrocardiography , Heart Failure/therapy , Cardiac Pacing, Artificial , Bundle of His , Treatment OutcomeABSTRACT
Cancer cells show enhanced nucleotide biosynthesis, which is essential for their unlimited proliferation, but the underlying mechanisms are not entirely clear. Ubiquitin specific peptidase 29 (USP29) was reported to sustain neuroblastoma progression by promoting glycolysis and glutamine catabolism; however, its potential role in regulating nucleotide biosynthesis in tumor cells remains unknown. In this study, we depleted endogenous USP29 in MYCN-amplified neuroblastoma SK-N-BE2 cells by sgRNAs and conducted metabolomic analysis in cells with or without USP29 depletion, we found that USP29 deficiency caused a disorder of intermediates involved in glycolysis and nucleotide biosynthesis. De novo nucleotide biosynthesis was analyzed using 13C6 glucose as a tracer under normoxia and hypoxia. The results indicated that USP29-depleted cells showed inhibition of nucleotide anabolic intermediates derived from glucose, and this inhibition was more significant under hypoxic conditions. Analysis of RNA sequencing data in SK-N-BE2 cells demonstrated that USP29 promoted the gene expression of metabolic enzymes involved in nucleotide anabolism, probably by regulating MYC and E2F downstream pathways. These findings indicated that USP29 is a key regulator of nucleotide biosynthesis in tumor cells.
Subject(s)
Multiomics , Neuroblastoma , Humans , RNA, Guide, CRISPR-Cas Systems , Neuroblastoma/pathology , Glycolysis , Glucose , Cell Line, Tumor , N-Myc Proto-Oncogene Protein/genetics , N-Myc Proto-Oncogene Protein/metabolism , Gene Expression Regulation, Neoplastic , Ubiquitin-Specific Proteases/metabolismABSTRACT
Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of disorders characterized by increased risk of infections, autoimmunity, autoinflammatory diseases, malignancy and allergy. Next-generation sequencing has revolutionized the identification of genetic background of these patients and assists in diagnosis and treatment. In this study, we identified a probable unique monogenic cause of IEI, and evaluated the immunological methods and pathogenic detections. Methods: A family with a member with a clinical diagnosis of IEI was screened by whole genomic sequencing (WGS). Demographic data, clinical manifestations, medical history, physical examination, laboratory findings and imaging features of the patient were extracted from medical records. Comprehensive immune monitoring methods include a complete blood count with differential, serum levels of cytokines and autoantibodies, T-cell and B-cell subsets analysis and measurement of serum immunoglobulins. In addition, metagenomic sequencing (mNGS) of blood, cerebrospinal fluid and biopsy from small intestine were used to detect potential pathogens. Results: The patient manifested with recurrent infections and autoimmune disorders, who was eventually diagnosed with IEI. Repetitive mNGS tests of blood, cerebrospinal fluid and biopsy from small intestine didn't detect pathogenic microorganism. Immunological tests showed a slightly decreased level of IgG than normal, elevated levels of tumor necrosis factor and interleukin-6. Lymphocyte flow cytometry showed elevated total B cells and natural killer cells, decreased total T cells and B-cell plasmablasts. WGS of the patient identified a novel heterozygous mutation in IRF2BP2 (c.439_450dup p. Thr147_Pro150dup), which was also confirmed in his father. The mutation was classified as variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics guidelines. Conclusion: We identified a novel IRF2BP2 mutation in a family with a member diagnosed with IEI. Immune monitoring and WGS as auxiliary tests are helpful in identifying genetic defects and assisting diagnosis in patients with clinically highly suspected immune abnormalities and deficiencies in inflammation regulation. In addition, mNGS techniques allow a more comprehensive assessment of the pathogenic characteristics of these patients. This report further validates the association of IRF2BP2 deficiency and IEI, and expands IEI phenotypes.
Subject(s)
Autoimmune Diseases , Reinfection , Humans , Autoimmune Diseases/diagnosis , Autoimmune Diseases/genetics , Autoantibodies , Autoimmunity , B-Lymphocytes , DNA-Binding Proteins , Transcription FactorsABSTRACT
Amorphous polymers with ultralong room-temperature phosphorescence (RTP) are highly promising for various applications. Particularly, polymer-based RTP materials with multiple functions such as color-tunability or stimulus-response are highly desirable for multilevel anti-counterfeiting but are rarely reported. Herein, a facile strategy is presented to achieve a series of polymer-based RTP materials with ultralong lifetime, multicolor afterglow, and reversible response to UV irradiation by simply embedding pyridine-substituted triphenylamine derivatives into the polymer matrix poly(vinyl alcohol) (PVA) and poly(methyl methacrylate) (PMMA), respectively. Notably, the pyridine group with the capabilities of promoting intersystem crossing and forming hydrogen-bonding interactions is essential for triggering ultralong RTP from the doping PVA system, among which the doping film TPA-2Py@PVA exhibits excellent RTP property with an ultralong lifetime of 798.4 ms and a high quantum yield of 15.2%. By further co-doping with the commercially available fluorescent dye, multicolor afterglow is obtained via phosphorescence energy transfer. Meanwhile, the doped PMMA system exhibits reversible photoactivated ultralong RTP properties under continuous UV irradiation. Finally, potential applications of these doped PVA and PMMA systems with ultralong lifetime, multicolor afterglow, and photoactivated ultralong RTP in multidimensional anti-counterfeiting are demonstrated.
Subject(s)
Polymethyl Methacrylate , Ultraviolet Rays , Temperature , Amines , Pyridines , PolymersABSTRACT
Individual pain sensitivity is modulated by the brain's structural and functional features, but its heritability remains unclear. This paper conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of neuroimage phenotypes of pain sensitivity. In total, 432 normal participants were divided into high and low pain sensitivity groups according to the laser quantitative test threshold. Then, the brain's gray matter density (GMD) features correlated with pain sensitivity were identified. Next, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results, the right insula was identified for further refined analysis in terms of subregions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than that in the low sensitivity group. Also, the TT/TC group at locus rs187974 has lower right insula GMD than the CC group. Further, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests that the right insula and multiple candidate loci may be importantly involved in pain sensitivity modulation, which may guide the future development of precision pain therapeutics.
Subject(s)
Genome-Wide Association Study , Quantitative Trait Loci , Humans , Magnetic Resonance Imaging , Brain/diagnostic imaging , Pain/genetics , PhenotypeABSTRACT
BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.
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Current studies have found that low-dose irradiation (IR) can promote bone regeneration. However, mechanism studies of IR-triggered bone regeneration mainly focus on the effects of osteoblasts, neglecting the role of the surrounding immune microenvironment. Here in this study, in vitro proliferation experiments showed that low-dose IR ≤2 Gy could promote the proliferation of bone marrow mesenchymal stem cells (BMSCs), and qRT-PCR assay showed that low-dose IR ≤2 Gy could exert the M2 polarization of Raw264.7 cells, while IR >2 Gy inhibited BMSC proliferation and triggered M1 polarization in Raw264.7 cells. The ALP and mineralized nodules staining showed that low-dose IR ≤2 Gy not only promoted osteoblast mineralization through IR-triggered osteoblast proliferation but also through M2 polarization of Raw264.7 cells, while high-dose IR >2 Gy had the opposite effect. The co-incubation of BMSC with low-dose IR irradiated Raw264.7 cell supernatants increased the mRNA expression of BMP-2 and Osx. The rat cranial defects model revealed that low-dose IR ≤2 Gy gradually promoted bone regeneration, while high-dose IR >2 Gy inhibited bone regeneration. Detection of macrophage polarity in peripheral blood samples showed that low-dose IR ≤2 Gy increased the expression of CD206 and CD163, but decreased the expression of CD86 and CD80 in macrophages, which indicated M2 polarization of macrophages in vivo, while high-dose IR had the opposite effect. Our finding innovatively revealed that low-dose IR ≤2 Gy promotes bone regeneration not only by directly promoting the proliferation of osteoblasts but also by triggering M2 polarization of macrophages, which provided a new perspective for immune mechanism study in the treatment of bone defects with low-dose IR.
Subject(s)
Macrophages , Mesenchymal Stem Cells , Mice , Rats , Animals , Macrophages/metabolism , RAW 264.7 Cells , Bone RegenerationABSTRACT
Introduction: This study investigated the impact of competition on supplier-induced demand in medical markets theoretically and experimentally. Methods: We employed the framework of credence goods to describe the information asymmetry between physicians and patients, and theoretically derives predictions of physicians' behaviors in monopolistic and competitive markets. Then we conducted behavioral experiments to empirically test the hypotheses. Results: The theoretical analysis revealed that an honest equilibrium would not exist in a monopolistic market, whereas price competition could induce physicians to reveal their types of treatment cost and provide honest treatments; thus, a competitive equilibrium is superior to that of a monopolistic market. The experimental results only partially supported the theoretical predictions, which showed that the cure rate of patients in a competitive environment was higher than that in a monopolistic market, although supplier-induced demand occurred more frequently. In the experiment, the main channel through which competition improved market efficiency was increased patient consultations through low pricing, as opposed to the theory, which stated that competition would lead to physicians' honest treatment of patients through fair prices. Discussion: We discovered that the divergence between the theory and the experiment stemmed from the theory's reliance on the assumption that humans are rational and self-interested, which means that they are not as price-sensitive as predicted by theory.
Subject(s)
Economic Competition , Induced Demand , Humans , Costs and Cost AnalysisABSTRACT
Unethical behavior is discovered that is more contagious than ethical behavior. This article attempts to propose one of the possible underlying mechanisms-people may have underconfidence bias in information updating due to motivated reasoning, and such bias exhibits in a different direction compared to the overconfident bias documented in the literature on ethical environment, which generate the asymmetric pattern in contagion. This study designs an experiment which relates the unethical behavior to social learning, where a series of subjects with private information about penalty decide sequentially whether to conduct unethical behavior publicly. This study adopts a quantal response equilibrium to construct a structural model for estimation of the bias. In total, 162 university students participated in our experiment and the results confirm the asymmetric patterns that people rely more on others' precedent decisions rather than their private signal; therefore, the bias facilitates the contagion. This study also tests two punishment systems in the experiment and the results suggest a policy: slightly increasing penalties for the "followers" in the early stages would effectively suppress the contagion.
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Myocardial infarction (MI) remains a major challenge to cardiovascular health worldwide, with poor healing leaving a direct impact on patients' quality of life and survival. Metabolic abnormalities after MI are receiving increasing attention. Our previous studies showed that enhancing proline catabolism ameliorates hypoxic damage to myocardial cells; therefore, we sought to determine whether reducing the synthesis of endogenous proline also affects MI. We analysed GEO datasets associated with MI and western blot of mouse heart tissue in an MI model to demonstrate pyrroline-5-carboxylate reductase 1 (Pycr1) expression level after MI. We constructed Pycr1 KO mice by CRISPR/Cas9 technology to explore the effect of Pycr1 gene KO after MI using transcriptomic and metabolomic techniques. In this study, we found reduced mRNA and protein expression levels of Pycr1 in the hearts of mice after MI. We observed that Pycr1 gene KO has a protective effect against MI, reducing the area of MI and improving heart function. Using transcriptomics approaches, we found 215 upregulated genes and 247 downregulated genes after KO of the Pycr1 gene, indicating that unsaturated fatty acid metabolism was affected at the transcriptional level. Metabolomics results revealed elevated content for 141 metabolites and decreased content for 90 metabolites, among which the levels of fatty acids, glycerol phospholipids, bile acids, and other metabolites increased significantly. The changes in these metabolites may be related to the protective effect of Pycr1 KO on the heart after MI. Pycr1 gene KO has a protective effect against MI and our research will lay a solid foundation for the development of future Pycr1-related drug targets.
Subject(s)
Myocardial Infarction , Pyrroline Carboxylate Reductases , Animals , Mice , Metabolomics , Myocardial Infarction/genetics , Proline , Pyrroline Carboxylate Reductases/genetics , Transcriptome/genetics , delta-1-Pyrroline-5-Carboxylate ReductaseABSTRACT
PURPOSE: His bundle pacing (HBP) improves heart failure (HF) in atrial fibrillation (AF) pacing-dependent patients with a potential for a progressively increased threshold. HBP with right ventricular pacing (RVP) as a backup is always the preferred choice; however, RVP may induce HF. His Purkinje system pacing (HPSP) includes HBP and left bundle branch area pacing (LBBAP). LBBAP maintains left ventricular synchrony but has not been proven to be safe over the long term. We assessed the feasibility and safety of both HBP and LBBAP in AF pacing-dependent patients and compared the parameters of both leads at baseline and at the 6-month follow-up. METHODS: A total of 16 AF patients in our center, who successfully attempted both HBP and LBBAP, were prospectively enrolled unless only one of these treatment statuses was attained. The electrocardiogram characteristics, leading parameters, echocardiography results, and clinical outcomes were assessed. RESULTS: Thirteen out of 16 patients achieved both HBP and LBBAP successfully in the same AF pacing-dependent patients. In symptomatic HF patients with preserved left ventricular ejection fraction (LVEF) (n = 10), the left ventricular end-diastolic diameter (LVEDD) was reduced from 51.8 ± 4.4 to 48.3 ± 3.1 mm (p = 0.01) with the use of diuretics, either reduced or stopped (n = 7). During the follow-up, one patient in the group without HF had an increased HBP threshold and developed HF symptoms. His HF symptoms disappeared when switched into LBBAP mode. Another patient in the group with HF got his LVEF elevated by HBP for 3 months by utilizing left bundle branch block(LBBB)correction and continued to increase when switched into LBBAP for another 3 months due to an increased HBP correction threshold. The average unipolar pacing threshold of LBBAP was lower than that of HBP. No perforation or dislodgement occurred in our study. CONCLUSION: Both HBP and LBBAP could be attempted successfully in the same AF patients when one of the two modes could be adopted and switched according to the clinical feasibility. Compared with HBP, LBBAP yielded better and more stable parameters but showed comparable effects during the 6-month follow-up.