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1.
ChemSusChem ; : e202401487, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39278837

ABSTRACT

2,5-Furandicarboxylic acid (FDCA) is a class of valuable biomass-based platform compounds. The creation of FDCA involves the catalytic oxidation of 5-hydroxymethylfurfural (HMF). As a novel catalytic method, electrocatalysis has been utilized in the 5-hydroxymethylfurfural oxidation reaction (HMFOR). Common noble metal catalysts show catalytic activity, which is limited by price and reaction conditions. Non-noble metal catalyst is known for its environmental friendliness, affordability and high efficiency. The development of energy efficient non-noble metal catalysts plays a crucial role in enhancing the HMFOR process. It can greatly upgrade the demand of industrial production, and has important research significance for electrocatalytic oxidation of HMF. In this paper, the reaction mechanism of HMF undergoes electrocatalytic oxidation to produce FDCA are elaborately summarized. There are two reaction pathways and two oxidation mechanisms of HMFOR discussed deeply. In addition, the speculation on the response of the electrode potential to HMFOR is presented in this paper. The main non-noble metal electrocatalysts currently used are classified and summarized by targeting metal element species. Finally, the paper focus on the mechanistic effects of non-noble metal catalysts in the reaction, and provide the present prospects and challenges in the electrocatalytic oxidation reaction of HMF.

2.
Psychol Res Behav Manag ; 17: 3083-3100, 2024.
Article in English | MEDLINE | ID: mdl-39220633

ABSTRACT

Purpose: Given that mother plays the main nurturing role in a family unit and their unique influence on children's development, the current study aimed to examine the influence of maternal phubbing on children's problematic media use and the independent and interactive moderating role of children's negative affectivity and effortful control. Methods: Participants were 1986 children aged 3 to 6 years in Shanghai, China. Their mothers were asked to complete a series of questionnaires including parental phubbing scale, problematic media use measure, and child behavior questionnaire. To investigate the moderating influence of children's negative affectivity and effortful control, hierarchical linear regression analyses were conducted using SPSS 24.0. Simple slopes analyses and the Johnson-Neyman technique were further used to depict moderation effects. Results: Maternal phubbing was associated with higher levels of problematic media use in preschool children (ß = 0.18, p <.001, [0.14, 0.22]). Children's negative affectivity acts as a risk factor, exacerbating the adverse effects of maternal phubbing on children's problematic media use (ß = 0.05, t = 2.69, p < 0.05), whereas children's effortful control acts as a protective factor, buffering the link between maternal phubbing and children's problematic media use (ß = -0.10, t = -5.00, p < 0.001). Conclusion: These results suggest that interventions seeking to promote appropriate digital development in preschoolers should take the child's temperament into account and be complemented by active parental mediation and involvement.

3.
Heliyon ; 10(16): e36009, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39224296

ABSTRACT

Background: Nursing can effectively prevent and ameliorate diabetic foot ulcers (DFU). However, there is a lack of literature on the bibliometric analysis of DFU nursing. This study aimed to analyze the research hotspots and development trends in DFU nursing over the past 10 years to provide references for future related research. Methods: The Web of Science Core Collection was used to retrieve literature related to DFU nursing from 2013 to 2023. Analyses included the annual publication trends; author, institution, and country collaborations; journal and literature co-citation; and keyword co-occurrence, clustering, and bursting, performed using CiteSpace 5.8 R3. Results: A total of 229 papers were included, showing an upward trend in annual publications. American scholar David G Armstrong (n = 3) and King's College Hospital London (n = 4) were the most productive authors and institutions, respectively. The United States ranked first (n = 45) in national contributions, followed by China and Brazil. The overall research strength between authors and institutions was relatively scattered, and intensive cooperation has not yet been formed. National collaborations resulted in a core team dominated by Europe and North America with concentrated research strengths. The most frequently co-cited journal and co-cited reference were Diabetes Care (111 citations) and Armstrong DG (2017) (131 citations), separately. Research hotspots mainly focused on risk assessment, classification systems, protective measures, and clinical management of DFU. "Primary care" and "intervention efficacy" were identified as the research trends in the coming years. Conclusion: The field of DFU nursing requires more attention. Academic exchange and cooperation between authors, institutions, and countries should be strengthened. Our future research will focus on the latest hotspots and trends, conducting more in-depth and comprehensive studies on DFU management.

4.
Food Chem ; 460(Pt 3): 140689, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39116767

ABSTRACT

Residues of pesticides in milk may pose a threat to human health. This study aimed to develop a liquid-phase microextraction (LPME) method using hexafluoroisopropanol (HFIP)-based supramolecular solvent (SUPRAS) for the simultaneous extraction and purification of four pesticides (boscalid, novaluron, cypermethrin and bifenthrin) in milk. Pesticides were extracted using SUPRAS prepared with nonanol and HFIP, and the extraction efficiency was analyzed. Results showed satisfactory recoveries ranging from 80.8%-111.0%, with relative standard deviations (RSDs) of <6.4%. Additionally, satisfactory linearities were observed, with correlation coefficients >0.9952. The limits of quantification (LOQs) were in the range of 1.8 µg·L-1-14.0 µg·L-1. The established method demonstrated high extraction efficiency with a short operation time (15 mins) and low solvent consumption (2.7 mL). The HFIP-based SUPRAS LPME method offers a convenient and efficient approach for the extraction of pesticides from milk, presenting a promising alternative to conventional techniques.


Subject(s)
Food Contamination , Liquid Phase Microextraction , Milk , Solvents , Liquid Phase Microextraction/methods , Milk/chemistry , Animals , Solvents/chemistry , Food Contamination/analysis , Pesticide Residues/isolation & purification , Pesticide Residues/chemistry , Pesticide Residues/analysis , Hexanols/chemistry , Cattle , Pesticides/isolation & purification , Pesticides/chemistry , Pesticides/analysis , Hydrocarbons, Fluorinated , Propanols
5.
Animals (Basel) ; 14(16)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39199957

ABSTRACT

The aim of this study was to investigate the effects of hypoxia-induced phenotype, glucose metabolism, ROS levels, and the PDK1-mediated regulation of TGF-ß/Smad signaling in yellow cattles, yaks, and those overexpressing PDK1 PASMCs using growth curves, flow cytometry, scratch experiments, glucose and lactic acid assays, RT-qPCR, and Western blotting. The results showed that hypoxia significantly promoted proliferation, migration, antiapoptosis, ROS levels, glucose consumption, and lactate production in yellow cattle PASMCs (p < 0.05), and the cells were dedifferentiated from the contractile phenotype; conversely, hypoxia had no significant effect on yak PASMCs (p > 0.05). PDK1 overexpression significantly promoted proliferation, antiapoptosis, glucose consumption, and lactate production in yak PASMCs under normoxia and hypoxia (p < 0.05), decreased their migration levels under hypoxia (p < 0.05), and dedifferentiated the contractile phenotype of the cells. Overexpression of PDK1 in yak PASMCs is detrimental to their adaptation to hypoxic environments. Yak PASMCs adapted to the effects of hypoxia on lung tissue by downregulating the expression of genes related to the PDK1 and TGF-ß/Smad signaling pathways. Taken together, the regulation of PDK1-mediated TGF-ß/Smad signaling may be involved in the process of yaks' adaptation to the hypoxic environment of the plateau, reflecting the good adaptive ability of yaks. The present study provides basic information to further elucidate the mechanism of PDK1-mediated TGF-ß/Smad signaling induced by hypoxia in the lungs of yaks, as well as target genes for the treatment of plateau diseases in humans and animals.

6.
Nat Commun ; 15(1): 7337, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39187565

ABSTRACT

There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe-/- mice lacking Vcam1 in macrophages. Downregulation of macrophage-specific VCAM-1 in vivo leads to decreased expression of LYZ1 and FCOR, involved in STING signalling. Finally, VCAM-1 expression in human carotid plaque macrophages correlates with necrotic core area, mitochondrial volume, and oxidative damage to DNA. Collectively, our study highlights the importance of macrophage VCAM-1 in inflammation and atherogenesis pathology and proposes a self-acerbating pathway involving increased mtDNA synthesis.


Subject(s)
Atherosclerosis , DNA, Mitochondrial , Inflammation , Macrophages , Membrane Proteins , Plaque, Atherosclerotic , Vascular Cell Adhesion Molecule-1 , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Animals , Vascular Cell Adhesion Molecule-1/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/genetics , Macrophages/metabolism , Humans , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Mice , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Male , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria/pathology , Mice, Knockout, ApoE , Signal Transduction , Female , Apolipoproteins E/genetics , Apolipoproteins E/metabolism
7.
Materials (Basel) ; 17(16)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39203278

ABSTRACT

The galvanic corrosion performance of AM60B coupled to DC01 was characterized in simulated environments with varying water salinity. The results showed that the coupled DC01 effectively accelerated the corrosion rate of AM60B, and the increased salt concentration had a significant effect on the deterioration process. The corrosion of AM60B mainly exhibits metal dissolution, and the formed Mg(OH)2 has weak a protective effect on the alloy substrate. Furthermore, the distributions of the corrosion potential and the corrosion current density of the AM60B/DC01 couple were simulated and intensively discussed.

8.
J Synchrotron Radiat ; 31(Pt 5): 1317-1326, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39190504

ABSTRACT

To date, computed tomography experiments, carried-out at synchrotron radiation facilities worldwide, pose a tremendous challenge in terms of the breadth and complexity of the experimental datasets produced. Furthermore, near real-time three-dimensional reconstruction capabilities are becoming a crucial requirement in order to perform high-quality and result-informed synchrotron imaging experiments, where a large amount of data is collected and processed within a short time window. To address these challenges, we have developed and deployed a synchrotron computed tomography framework designed to automatically process online the experimental data from the synchrotron imaging beamlines, while leveraging the high-performance computing cluster capabilities to accelerate the real-time feedback to the users on their experimental results. We have, further, integrated it within a modern unified national authentication and data management framework, which we have developed and deployed, spanning the entire data lifecycle of a large-scale scientific facility. In this study, the overall architecture, functional modules and workflow design of our synchrotron computed tomography framework are presented in detail. Moreover, the successful integration of the imaging beamlines at the Shanghai Synchrotron Radiation Facility into our scientific computing framework is also detailed, which, ultimately, resulted in accelerating and fully automating their entire data processing pipelines. In fact, when compared with the original three-dimensional tomography reconstruction approaches, the implementation of our synchrotron computed tomography framework led to an acceleration in the experimental data processing capabilities, while maintaining a high level of integration with all the beamline processing software and systems.

9.
Exp Parasitol ; 265: 108813, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39117169

ABSTRACT

Babesia duncani, responsible for human babesiosis, is one of the most important tick-borne intraerythrocytic pathogens. Traditionally, babesiosis is definitively diagnosed by detecting parasite DNA in blood samples and examining Babesia parasites in Giemsa-stained peripheral blood smears. Although these techniques are valuable for determining Babesia duncani, they are often time-consuming and laborious. Therefore, developing rapid and reliable B. duncani identification assays is essential for subsequent epidemiological investigations and prevention and control. In this study, a cross-priming amplification (CPA) assay was developed, combined with a vertical flow visualization strip, to rapidly and accurately detect B. duncani infection. The detection limit of this method was as low as 0.98 pg/µl of genomic DNA from B. duncani merozoites per reaction at 59 °C for 60 min. There were no cross-reactions between B. duncani and other piroplasms infective to humans and mammals. A total of 592 blood samples from patients bitten by ticks and experimental infected hamsters were accurately assessed using CPA assay. The average cost of the CPA assay is as low as approximately $ 0.2 per person. These findings indicate that the CPA assay may therefore be a rapid screening tool for detection B. duncani infection, based on its accuracy, speed, and cost-effectiveness, particularly in resource-limited regions with a high prevalence of human babesiosis.


Subject(s)
Babesia , Babesiosis , DNA, Protozoan , Nucleic Acid Amplification Techniques , Sensitivity and Specificity , Animals , Babesiosis/diagnosis , Babesiosis/parasitology , Babesia/isolation & purification , Babesia/genetics , Babesia/classification , Humans , Nucleic Acid Amplification Techniques/methods , Nucleic Acid Amplification Techniques/economics , Nucleic Acid Amplification Techniques/standards , DNA, Protozoan/isolation & purification , DNA, Protozoan/blood , DNA, Protozoan/analysis , Cricetinae , Limit of Detection
10.
J Psychosom Res ; 185: 111868, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39142194

ABSTRACT

OBJECTIVE: The dorsolateral prefrontal cortex (DLPFC) is implicated in pain modulation, suggesting its potential as a therapeutic target for pain relief. However, studies on transcranial electrical stimulation (tES) over the DLPFC yielded diverse results, likely due to differences in stimulation protocols or pain assessment methods. This study aims to evaluate the analgesic effects of DLPFC-tES using a meta-analytical approach. METHODS: A meta-analysis of 29 studies involving 785 participants was conducted. The effects of genuine and sham DLPFC-tES on pain perception were examined in healthy individuals and patients with clinical pain. Subgroup analyses explored the impact of stimulation parameters and pain modalities. RESULTS: DLPFC-tES did not significantly affect pain outcomes in healthy populations but showed promise in reducing pain-intensity ratings in patients with clinical pain (Hedges' g = -0.78, 95% CI = [-1.33, -0.24], p = 0.005). Electrode placement significantly influenced the analgesic effect, with better results observed when the anode was at F3 and the cathode at F4. CONCLUSIONS: DLPFC-tES holds potential as a cost-effective pain management option, particularly for clinical populations. Optimizing electrode placement, especially with an symmetrical configuration, may enhance therapeutic efficacy. These findings underscore the promise of DLPFC-tES for alleviating perceived pain intensity in clinical settings, emphasizing the importance of electrode placement optimization.


Subject(s)
Dorsolateral Prefrontal Cortex , Pain Management , Transcranial Direct Current Stimulation , Humans , Transcranial Direct Current Stimulation/methods , Dorsolateral Prefrontal Cortex/physiology , Pain Management/methods , Analgesia/methods , Prefrontal Cortex/physiology
11.
BMC Psychol ; 12(1): 409, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39061084

ABSTRACT

The COVID-19 pandemic has had an inestimable impact worldwide, challenging the daily lives and interactions of children and their families. In 2022, Shanghai implemented a three-month lockdown in response to an acceleration of positive cases during the pandemic period. This restrictive policy provided insight into the impact of the lockdown on children's social adjustment and the role of parent-child conflict during this process. Mothers of preschool-aged children participated in this study and completed the Chinese version of Child-Parent Relationship Scale (CPRS) and the Strengths and Difficulties Questionnaire (SDQ). Using Propensity Score Matching (PSM) method, two matched groups were formed: pre-lockdown group and post-lockdown group, with a total of 574 preschoolers (N = 297 in each group; Mage = 4.36, SD = 0.86) were recruited. The results showed that the lockdown directly impacted children's emotional symptoms. Additionally, the parent-child conflict mediated relationship between the lockdown and children's adjustment. Specifically, parent-child conflict deteriorated children's emotional symptoms, hyperactivity-attention problems, and prosocial behaviors. These findings highlight the significant impact of the severe lockdown on children's social adjustment and the role of parent-child interactions during this period.


Subject(s)
COVID-19 , Propensity Score , Humans , COVID-19/psychology , COVID-19/prevention & control , COVID-19/epidemiology , Female , Child, Preschool , Male , China , Social Adjustment , Parent-Child Relations , Quarantine/psychology , Surveys and Questionnaires , SARS-CoV-2
12.
Front Biosci (Landmark Ed) ; 29(7): 271, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39082345

ABSTRACT

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants characterized by alveolar dysplasia, vascular simplification and dysmorphic vascular development. Supplemental oxygen and mechanical ventilation commonly used as life-saving measures in premature infants may cause BPD. microRNAs (miRNAs), a class of small, non-coding RNAs, regulate target gene expression mainly through post-transcriptional repression. miRNAs play important roles in modulating oxidative stress, proliferation, apoptosis, senescence, inflammatory responses, and angiogenesis. These cellular processes play pivotal roles in the pathogenesis of BPD. Accumulating evidence demonstrates that miRNAs are dysregulated in the lung of premature infants with BPD, and in animal models of this disease, suggesting contributing roles of dysregulated miRNAs in the development of BPD. Therefore, miRNAs are considered promising biomarker candidates and therapeutic agents for this disease. In this review, we discuss how dysregulated miRNAs and their modulation alter cellular processes involved in BPD. We then focus on therapeutic approaches targeting miRNAs for BPD. This review provides an overview of miRNAs as biomarkers, and highlights potential pathogenic roles, and therapeutic strategies for BPD using miRNAs.


Subject(s)
Biomarkers , Bronchopulmonary Dysplasia , MicroRNAs , Bronchopulmonary Dysplasia/genetics , Bronchopulmonary Dysplasia/metabolism , Bronchopulmonary Dysplasia/therapy , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers/metabolism , Infant, Newborn , Animals , Infant, Premature
13.
Clin Cancer Res ; 30(17): 3919-3936, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-38900040

ABSTRACT

PURPOSE: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA sequencing (scRNA-seq) to paired diagnostic and posttreatment bone marrow (BM) samples. EXPERIMENTAL DESIGN: scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (n = 1), MM patients at diagnosis (n = 19), MM posttreatment (n = 17), and one healthy donor (HD). The single-cell transcriptome data of malignant plasma cells (PC) and the surrounding immune microenvironment were analyzed. RESULTS: Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD-) and clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift toward fatty acid oxidation in cycling-resistant PCs, whereas selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and nongenetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant PCs and the tumor microenvironment. Selective PCs showed the most robust cellular interactions with the tumor microenvironment. CONCLUSIONS: These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in MM.


Subject(s)
Clonal Evolution , Drug Resistance, Neoplasm , Multiple Myeloma , Neoplasm, Residual , Single-Cell Analysis , Tumor Microenvironment , Humans , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Multiple Myeloma/drug therapy , Single-Cell Analysis/methods , Clonal Evolution/genetics , Neoplasm, Residual/genetics , Neoplasm, Residual/pathology , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Drug Resistance, Neoplasm/genetics , Female , Male , Middle Aged , Transcriptome , Aged , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Plasma Cells/pathology , Plasma Cells/metabolism , Plasma Cells/immunology , Bone Marrow/pathology
14.
BMJ Open ; 14(6): e078687, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858136

ABSTRACT

OBJECTIVES: This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). DESIGN: Clinical retrospective cross-sectional study. SETTING: A comprehensive teaching tertiary hospital in China. PARTICIPANTS: Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. MAIN OUTCOME MEASURES: HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. RESULTS: Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. CONCLUSIONS: HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.


Subject(s)
Antimicrobial Cationic Peptides , Biomarkers , Blood Proteins , C-Reactive Protein , Intensive Care Units , Organ Dysfunction Scores , Sepsis , Humans , Retrospective Studies , Cross-Sectional Studies , Female , Male , Biomarkers/blood , Middle Aged , Sepsis/diagnosis , Sepsis/blood , China , Aged , Blood Proteins/analysis , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Antimicrobial Cationic Peptides/blood , Procalcitonin/blood , APACHE , Interleukin-6/blood , Adult , ROC Curve , Lactic Acid/blood
15.
Arthritis Res Ther ; 26(1): 119, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38863059

ABSTRACT

OBJECTIVE: In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1ß. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU. METHODS: BMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer. RESULTS: We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1ß levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1ß. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1ß in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1ß by peripheral blood mononuclear cells from healthy donors. CONCLUSION: Our data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.


Subject(s)
Arthritis, Gouty , CD11b Antigen , Inflammasomes , Macrophages , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Uric Acid , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Macrophages/metabolism , CD11b Antigen/metabolism , Inflammasomes/metabolism , Arthritis, Gouty/chemically induced , Arthritis, Gouty/metabolism , Mice , Male
16.
Phytomedicine ; 130: 155537, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38823344

ABSTRACT

BACKGROUND: Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects. OBJECTIVE: Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms. STUDY DESIGN: For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice. METHODS: In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation. RESULTS: In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability. CONCLUSION: In summary, our research reveals that PT increases STUB1 m6A modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.


Subject(s)
Autophagy , Methyltransferases , Mice, Inbred BALB C , Mice, Nude , Triple Negative Breast Neoplasms , Ubiquitin-Protein Ligases , Animals , Triple Negative Breast Neoplasms/drug therapy , Humans , Autophagy/drug effects , Female , Cell Line, Tumor , Methyltransferases/metabolism , Ubiquitin-Protein Ligases/metabolism , Mice, SCID , Mice, Inbred NOD , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Xenograft Model Antitumor Assays , Panax/chemistry , Adenosine/analogs & derivatives , Adenosine/pharmacology
17.
Adipocyte ; 13(1): 2360037, 2024 12.
Article in English | MEDLINE | ID: mdl-38829527

ABSTRACT

As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4+ memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel's condensed nature.


Subject(s)
Adipose Tissue , Extracellular Matrix , Stromal Vascular Fraction , Humans , Female , Extracellular Matrix/metabolism , Adipose Tissue/metabolism , Adipose Tissue/cytology , Stromal Vascular Fraction/metabolism , Adult , Macrophages/metabolism , Macrophages/immunology , Adipocytes/metabolism , Adipocytes/cytology , Gels , Transcriptome
18.
Chemosphere ; 359: 142323, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38735496

ABSTRACT

Anoxygenic phototrophic bacteria is a promising catalyst for constructing bioanode, but the mixed culture with non-photosynthetic bacteria is inevitable in an open environment application. In this study, a Rhodopseudomonas-dominated mixed culture with other electrogenic bacteria was investigated for deciphering the differentiated performance on electricity generation in light or dark conditions. The kinetic study showed that reaction rate of OM degradation was 9 times higher than that under dark condition, demonstrating that OM degradation was enhanced by photosynthesis. However, CE under light condition was lower. It indicated that part of OM was used to provide hydrogen donors for the fixation of CO2 or hydrogen production in photosynthesis, decreasing the OM used for electron transfer. In addition, higher COD concentration was not conducive to electricity generation. EIS analysis demonstrated that higher OM concentration would increase Rct to hinder the transfer of electrons from bacteria to the electrode. Indirect and direct electron transfer were revealed by CV analysis for light and dark biofilm, respectively, and nanowires were also observed by SEM graphs, further revealing the differentiate performance. Microbial community analysis demonstrated Rhodopseudomonas was dominated in light and decreased in dark, but Geobacter increased apparently from light to dark, resulting in different power generation performance. The findings revealed the differentiated performance on electricity generation and pollutant removal by mixed culture of phototrophic bacteria in light or dark, which will improve the power generation from photo-microbial fuel cells.


Subject(s)
Bioelectric Energy Sources , Electricity , Rhodopseudomonas , Rhodopseudomonas/metabolism , Photosynthesis , Light , Electrodes , Biofilms/growth & development , Biological Oxygen Demand Analysis , Electron Transport , Geobacter/metabolism , Geobacter/physiology
19.
Carbohydr Polym ; 337: 122147, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710554

ABSTRACT

Treatment of infected wound by simultaneously eliminating bacteria and inducing angiogenesis to promote wound tissue regeneration remains a clinical challenge. Dynamic and reversable hydrogels can adapt to irregular wound beds, which have raised great attention as wound dressings. Herein, a sprayable chitosan-based hydrogel (HPC/CCS/ODex-IGF1) was developed using hydroxypropyl chitosan (HPC), caffeic acid functionalized chitosan (CCS), oxidized dextran (ODex) to crosslink through the dynamic imine bond, which was pH-responsive to the acidic microenvironment and could controllably release insulin growth factor-1 (IGF1). The HPC/CCS/ODex-IGF1 hydrogels not only showed self-healing, self-adaptable and sprayable properties, but also exhibited excellent antibacterial ability, antioxidant property, low-cytotoxicity and angiogenetic activity. In vivo experiments demonstrated that hydrogels promoted tissue regeneration and healing of bacteria-infected wound with a rate of approximately 98.4 % on day 11 by eliminating bacteria, reducing inflammatory and facilitating angiogenesis, demonstrating its great potential for wound dressing.


Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Neovascularization, Physiologic , Wound Healing , Animals , Humans , Male , Mice , Angiogenesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Bandages , Chitosan/chemistry , Chitosan/pharmacology , Dextrans/chemistry , Dextrans/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Insulin-Like Growth Factor I , Neovascularization, Physiologic/drug effects , Staphylococcus aureus/drug effects , Wound Healing/drug effects , Wound Infection/drug therapy , Wound Infection/microbiology
20.
Z Gastroenterol ; 62(9): 1379-1383, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38604219

ABSTRACT

Carrilizumab, a PD-1 inhibitor, has shown therapeutic effectiveness in patients with late-stage or metastatic solid tumors exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). dMMR/MSI-H cancer patients are known to be responsive to PD-1 inhibitors. However, the use of carrilizumab for preoperative immunotherapy in early, unresectable MSI-H/dMMR primary colon cancer lesions is relatively underexplored. We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tenderness or palpable masses. Following radical colectomy, the primary tumor exhibited a pathological complete response. This case highlights the potential of preoperative neoadjuvant immunotherapy to improve staging accuracy and increase surgical resection rates in T4b MSI-H colon cancer patients without distant metastasis, suggesting a need for reconsideration of the treatment approach.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Microsatellite Instability , Neoadjuvant Therapy , Humans , Male , Middle Aged , Colorectal Neoplasms, Hereditary Nonpolyposis/therapy , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Colonic Neoplasms/therapy , Colonic Neoplasms/pathology , Adenocarcinoma/therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Immunotherapy , Colectomy
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