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1.
Int J Biol Macromol ; : 132355, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38754677

ABSTRACT

In this paper, a novel programable sewage-cleaning technology for the regeneration of antibacterial nanocomposites via the removal of wastewater pollutants is presented. Montmorillonite (MMT) was encapsulated in poly(vinyl alcohol) (PVA)-enhanced chitosan (CTS) hydrogels to form MMT-loaded nanocomposite biofilms (PCM). The PCM nanocomposite biofilms exhibited increased breaking strength and elongation at break, by factors of approximately 1.38 and 1.40, respectively, compared with those of the pure PVA/CTS biofilms. The maximum adsorption capacity of the PCM nanocomposite biofilms toward tetracycline and Ag(I) is 275.0 and 567.0 mg/g, respectively. The adsorbed nanocomposite biofilms exhibited excellent antibacterial properties against Staphylococcus aureus and Escherichia coli. Meanwhile, the nanocomposite also showed an effective adsorption capacity toward other toxic components, where the highest adsorption capacity is 2748.0 mg/g (for methyl blue). The simulation results indicated that the adsorption behaviors of the malachite green, neutral red, methyl blue, tetracycline, Cu(II), Zn(II), and Ag(I) by the PCM nanocomposite biofilms followed pseudo-second-order kinetic and Freundlich isotherm models. Furthermore, the PCM nanocomposite biofilms are stable in PBS solution but degradable in lysozyme-containing PBS solution, suggesting their potential application in the wastewater treatment as well as antibacterial fields.

2.
Materials (Basel) ; 17(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38730743

ABSTRACT

Considering the high-speed and high power density technical specifications of new energy vehicle motors, there is a growing demand for rotor strength as motor peak speeds reach 20,000 r/min and beyond. The utilization of non-oriented silicon steel with a high yield strength in rotors has emerged as a promising approach to increase motor speed. However, the magnetic and mechanical properties of high-strength silicon steel under variable temperature conditions have not been fully explored, particularly in regards to their impact on motor torque, efficiency, and speed. This manuscript investigates the behavior of high-strength silicon steel before and after annealing and at different temperatures, analyzing its influence on high-speed motor performance. The validity and feasibility of this study are confirmed through prototype testing, providing a comprehensive reference for engineering design.

3.
Burns Trauma ; 12: tkae006, 2024.
Article in English | MEDLINE | ID: mdl-38716051

ABSTRACT

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

4.
Food Chem ; 451: 139461, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38701733

ABSTRACT

Copper as a widely applied element in food supply chain can cause serious contamination issues that threats food safety. In this research, we present a quick and visible method for trace copper ion (Cu2+) quantification in practical food samples. Polymer dots (Pdots) were firstly conjugated with a copper-specific DNA aptamer and then tailored with rhodamine B (RhB) to extinguish the electrochemiluminescence (ECL) signal through a resonance energy transfer process. The selective release of RhB leads to signal restoration when exposed to trace Cu2+ levels, achieving remarkable linearity with the logarithm of Cu2+ concentration within the range of 1 ng/L to 10 µg/L with an impressively low limit of detection at 11.8 pg/L. Most notably, our device was also applicable on visualizing and quantifying trace Cu2+ (∼0.2 µg/g) in practical Glycyrrhiza uralensis Fisch. samples, underscoring its potential as a tool for the early prevention of potential copper contamination in food samples.

5.
Commun Biol ; 7(1): 594, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760406

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2-/-/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD-induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3ß pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.


Subject(s)
Adenosine Deaminase , Diet, High-Fat , Mice, Knockout , Non-alcoholic Fatty Liver Disease , RNA-Binding Proteins , Signal Transduction , Animals , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Adenosine Deaminase/deficiency , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Mice , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/etiology , Diet, High-Fat/adverse effects , Male , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Insulin Resistance , Mice, Obese , Obesity/metabolism , Obesity/genetics , Mice, Inbred C57BL , Liver/metabolism
6.
Cell Death Dis ; 15(4): 289, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653973

ABSTRACT

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.


Subject(s)
Breast Neoplasms , Cell Movement , GATA4 Transcription Factor , Gene Expression Regulation, Neoplastic , Histone Deacetylase 1 , Matrix Metalloproteinase 9 , Neoplasm Invasiveness , Humans , GATA4 Transcription Factor/metabolism , GATA4 Transcription Factor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Female , Cell Movement/genetics , Histone Deacetylase 1/metabolism , Histone Deacetylase 1/genetics , Animals , Acetylation , Cell Line, Tumor , Mice , Transcription Factor RelA/metabolism , Transcription, Genetic , Promoter Regions, Genetic/genetics , Mice, Nude , Mice, Inbred BALB C
7.
Neuroreport ; 35(9): 584-589, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38687896

ABSTRACT

OBJECTIVE: This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies. METHODS: Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content. RESULTS: The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence. CONCLUSION: The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension.


Subject(s)
Electroencephalography , Emotions , Evoked Potentials , Reading , Humans , Emotions/physiology , Evoked Potentials/physiology , Female , Male , Young Adult , Brain/physiology , Adult , Comprehension/physiology
8.
Nat Chem Biol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649452

ABSTRACT

The stabilization of stalled forks has emerged as a crucial mechanism driving resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient tumors. Here, we identify UFL1, a UFM1-specific E3 ligase, as a pivotal regulator of fork stability and the response to PARP inhibitors in BRCA1/2-deficient cells. On replication stress, UFL1 localizes to stalled forks and catalyzes the UFMylation of PTIP, a component of the MLL3/4 methyltransferase complex, specifically at lysine 148. This modification facilitates the assembly of the PTIP-MLL3/4 complex, resulting in the enrichment of H3K4me1 and H3K4me3 at stalled forks and subsequent recruitment of the MRE11 nuclease. Consequently, loss of UFL1, disruption of PTIP UFMylation or overexpression of the UFM1 protease UFSP2 protects nascent DNA strands from extensive degradation and confers resistance to PARP inhibitors in BRCA1/2-deficient cells. These findings provide mechanistic insights into the processes underlying fork instability in BRCA1/2-deficient cells and offer potential therapeutic avenues for the treatment of BRCA1/2-deficient tumors.

9.
Clin Proteomics ; 21(1): 30, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649851

ABSTRACT

BACKGROUND: Cardio-metabolic disorders (CMDs) are common in aging people and are pivotal risk factors for cardiovascular diseases (CVDs). Inflammation is involved in the pathogenesis of CVDs and aging, but the underlying inflammatory molecular phenotypes in CMDs and aging are still unknown. METHOD: We utilized multiple proteomics to detect 368 inflammatory proteins in the plasma of 30 subjects, including healthy young individuals, healthy elderly individuals, and elderly individuals with CMDs, by Proximity Extension Assay technology (PEA, O-link). Protein-protein interaction (PPI) network and functional modules were constructed to explore hub proteins in differentially expressed proteins (DEPs). The correlation between proteins and clinical traits of CMDs was analyzed and diagnostic value for CMDs of proteins was evaluated by ROC curve analysis. RESULT: Our results revealed that there were 161 DEPs (adjusted p < 0.05) in normal aging and EGF was the most differentially expressed hub protein in normal aging. Twenty-eight DEPs were found in elderly individuals with CMDs and MMP1 was the most differentially expressed hub protein in CMDs. After the intersection of DEPs in aging and CMDs, there were 10 overlapping proteins: SHMT1, MVK, EGLN1, SLC39A5, NCF2, CXCL6, IRAK4, REG4, PTPN6, and PRDX5. These proteins were significantly correlated with the level of HDL-C, TG, or FPG in plasma. They were verified to have good diagnostic value for CMDs in aging with an AUC > 0.7. Among these, EGLN1, NCF2, REG4, and SLC39A2 were prominently increased both in normal aging and aging with CMDs. CONCLUSION: Our results could reveal molecular markers for normal aging and CMDs, which need to be further expanded the sample size and to be further investigated to predict their significance for CVDs.

10.
Int J Neonatal Screen ; 10(2)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38651393

ABSTRACT

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.

11.
Sci Rep ; 14(1): 9824, 2024 04 29.
Article in English | MEDLINE | ID: mdl-38684755

ABSTRACT

PANoptosis plays a crucial role in cancer initiation and progression. However, the roles of PANoptosis-related genes (PARGs) in the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC) remain unclear. Integrated bioinformatics analyses based on the data of HNSCC patients in the TCGA database were conducted. We extracted 48 PARGs expression profile and then conducted differentially expressed analysis, following building a Cox model to predict the survival of HNSCC patients. Subsequently, the relationships between the risk score, immune landscape, chemo-, and immune-therapy responses were analyzed, respectively. Moreover, we investigated the prognostic value, and further predicted the pathways influenced by PARGs. Finally, we identified the biological function of crucial PARGs. A total of 18 differentially expressed PARGs were identified in HNSCC, and a Cox model including CASP8, FADD, NLRP1, TNF, and ZBP1 was constructed, which showed that the risk score was associated with the prognosis as well as immune infiltration of HNSCC patients, and the risk score could be regarded as an independent biomarker. Additionally, patients with high-risk score might be an indicator of lymph node metastasis and advanced clinical stage. High-risk scores also contributed to the chemotherapy resistance and immune escape of HNSCC patients. In addition, FADD and ZBP1 played a crucial role in various cancer-related pathways, such as the MAPK, WNT, and MTOR signaling pathways. On the other hand, we suggested that FADD facilitated the progression and 5-fluorouracil (5-FU) resistance of HNSCC cells. A signature based on PANoptosis showed great predictive power for lymph node metastasis and advanced stage, suggesting that the risk score might be an independent prognostic biomarker for HNSCC. Meanwhile, FADD, identified as a prognostic biomarker, may represent an effective therapeutic target for HNSCC.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/mortality , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Female , Male , Computational Biology/methods , Gene Expression Profiling , Fas-Associated Death Domain Protein/metabolism , Fas-Associated Death Domain Protein/genetics , Lymphatic Metastasis
12.
J Biol Chem ; 300(5): 107260, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38582447

ABSTRACT

Thoracic aortic dissection (TAD) is a highly dangerous cardiovascular disorder caused by weakening of the aortic wall, resulting in a sudden tear of the internal face. Progressive loss of the contractile apparatus in vascular smooth muscle cells (VSMCs) is a major event in TAD. Exploring the endogenous regulators essential for the contractile phenotype of VSMCs may aid the development of strategies to prevent TAD. Krüppel-like factor 15 (KLF15) overexpression was reported to inhibit TAD formation; however, the mechanisms by which KLF15 prevents TAD formation and whether KLF15 regulates the contractile phenotype of VSMCs in TAD are not well understood. Therefore, we investigated these unknown aspects of KLF15 function. We found that KLF15 expression was reduced in human TAD samples and ß-aminopropionitrile monofumarate-induced TAD mouse model. Klf15KO mice are susceptible to both ß-aminopropionitrile monofumarate- and angiotensin II-induced TAD. KLF15 deficiency results in reduced VSMC contractility and exacerbated vascular inflammation and extracellular matrix degradation. Mechanistically, KLF15 interacts with myocardin-related transcription factor B (MRTFB), a potent serum response factor coactivator that drives contractile gene expression. KLF15 silencing represses the MRTFB-induced activation of contractile genes in VSMCs. Thus, KLF15 cooperates with MRTFB to promote the expression of contractile genes in VSMCs, and its dysfunction may exacerbate TAD. These findings indicate that KLF15 may be a novel therapeutic target for the treatment of TAD.

13.
Nat Prod Res ; : 1-10, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38635344

ABSTRACT

Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of Ampelopsis japonica resulted in the isolation of two new triterpenoids (1-2), designated Ampejaponoside A and B, along with sixteen known compounds (3-18). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds 3-18 confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity in vitro. As a result, compounds 2, 8, and 14-16 displayed significant XOD inhibitory effect, particularly 16 being the most potent with an IC50 value of 0.21 µM, superior to positive substance allopurinol (IC50 1.95 µM). Molecular docking uncovered a unique interaction mode of 16 with the active site of XOD. The current study showed that the triterpenoids and polyphenols from A. japonica could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.

14.
RSC Adv ; 14(17): 12142-12146, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38628470

ABSTRACT

MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.

15.
Molecules ; 29(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611780

ABSTRACT

This study investigates the synthesis of mesophase pitch using low-cost fluid catalytic cracking (FCC) slurry and waste fluid asphaltene (WFA) as raw materials through the co-carbonization method. The resulting mesophase pitch product and its formation mechanism were thoroughly analyzed. Various characterization techniques, including polarizing microscopy, softening point measurement, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), were employed to characterize and analyze the properties and structure of the mesophase pitch. The experimental results demonstrate that the optimal optical texture of the mesophase product is achieved under specific reaction conditions, including a temperature of 420 °C, pressure of 1 MPa, reaction time of 6 h, and the addition of 2% asphaltene. It was observed that a small amount of asphaltene contributes to the formation of mesophase pitch spheres, facilitating the development of the mesophase. However, excessive content of asphaltene may cover the surface of the mesophase spheres, impeding the contact between them and consequently compromising the optical texture of the mesophase pitch product. Furthermore, the inclusion of asphaltene promotes polymerization reactions in the system, leading to an increase in the average molecular weight of the mesophase pitch. Notably, when the amount of asphaltene added is 2%, the mesophase pitch demonstrates the lowest ID/IG value, indicating superior molecular orientation and larger graphite-like microcrystals. Additionally, researchers found that at this asphaltene concentration, the mesophase pitch exhibits the highest degree of order, as evidenced by the maximum diffraction angle (2θ) and stacking height (Lc) values, and the minimum d002 value. Moreover, the addition of asphaltene enhances the yield and aromaticity of the mesophase pitch and significantly improves the thermal stability of the resulting product.

16.
CNS Neurosci Ther ; 30(4): e14710, 2024 04.
Article in English | MEDLINE | ID: mdl-38615363

ABSTRACT

AIMS: The present study aimed to explore the effect of cortico-cortical paired-associative stimulation (ccPAS) in modulating hyperdirect pathway and its influence on balance performance. METHODS: Forty healthy participants were randomly allocated to the active ccPAS group (n = 20) or the sham ccPAS group (n = 20). The primary motor cortex and subthalamic nucleus were stimulated sequentially with ccPAS. Unlike the active ccPAS group, one wing of coil was tilted to form a 90° angle with scalp of stimulation locations for the sham ccPAS group. Magnetic resonance imaging, functional reach test (FRT), timed up and go (TUG) test, and limit of stability (LOS) test were performed, and correlation between them was also analyzed. RESULTS: Three participants in the sham ccPAS group were excluded because of poor quality of NIfTI images. The active group had strengthened hyperdirect pathway, increased functional connectivity (FC) between orbital part of frontal cortex and bilateral precuneus, and decreased FC among basal ganglia (all p < 0.05). Regional network properties of triangular and orbital parts of IFG, middle cingulate cortex, and hippocampus increased. The active group performed better in FRT and LOS (all p < 0.05). FRT positively correlated with FC of the hyperdirect pathway (r = 0.439, p = 0.007) and FCs between orbital part of frontal cortex and bilateral precuneus (all p < 0.05). CONCLUSION: The ccPAS enhanced balance performance by promotion-like plasticity mechanisms through the hyperdirect pathway.


Subject(s)
Brain , Subthalamic Nucleus , Humans , Brain/diagnostic imaging , Scalp , Basal Ganglia , Frontal Lobe
17.
Acta Biomater ; 180: 82-103, 2024 May.
Article in English | MEDLINE | ID: mdl-38621599

ABSTRACT

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.


Subject(s)
Bone Regeneration , Bone Substitutes , Calcium Phosphates , Osteoporosis , Oxidative Stress , Oxidative Stress/drug effects , Animals , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Bone Regeneration/drug effects , Osteoporosis/pathology , Osteoporosis/therapy , Osteoporosis/drug therapy , Calcium Phosphates/pharmacology , Calcium Phosphates/chemistry , Rats, Sprague-Dawley , Selenium/chemistry , Selenium/pharmacology , Female , Osteogenesis/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Rats , Injections
18.
Adv Healthc Mater ; : e2304381, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38549217

ABSTRACT

Corneal injury occurs frequently which may lead to serious visual impairment. Rapid and efficient re-epithelialization after corneal epithelial injury is the key issue for maintaining corneal homeostasis. Among various treatment strategies, microRNA (miR)-based therapy shows great potential. However, structural limitations of miRNAs hinder its biomedical functionality. Nucleic acid nanotechnology is an appealing candidate for gene delivery because of its flexible modification and excellent biocompatibility. Herein, modified 3D tetrahedral framework nucleic acids (tFNAs) utilized as gene carriers for miR-21 delivery are constructed. TFNAs-miR-21 (T-21) shows great enzymatic resistance in extracellular environment and payload delivery into human corneal epithelial cells (HCECs) via clathrin-mediated endocytosis. T-21 facilitates proliferation and migration in HCECs via activating PI3K/AKT and ERK1/2 signaling pathways in vitro. In vivo studies, T-21 can be internalized by corneal epithelium in mice. In the mice corneal scratch model, T-21 ophthalmic solutions used as eye drops show no apparent side effects on the ocular surface histologically and exert great potential in accelerating corneal wound healing. These findings demonstrate that modified tFNAs are promising candidates for miRNA delivery for corneal wound healing. The convenient administration and great biocompatibility of tetrahedral DNA nanoparticles highlight its potential as gene transporter in solving ocular problems.

19.
ACS Omega ; 9(11): 13183-13190, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38524484

ABSTRACT

Nitrogen-doped carbon dots (NCD) with high fluorescence retention and good stability were successfully fabricated using citric acid and urea via a facile and eco-friendly one-step microwave method, which exhibited superior specificity for detection of nitrofurantoin (NFT). Upon the addition of NFT, the fluorescence intensity of NCD at 450 nm was significantly decreased. Besides, a satisfactory linear relationship between the fluorescence quenching efficiency and concentrations of NFT was obtained. Especially, NCD was qualitatively and quantitatively applied for detection NFT in milk and meat extract samples with a high recovery rate. Consequently, it was suggested that the detection method had potential application in the specific detection of NFT, offering a novel approach for veterinary drug residue detection.

20.
Nat Commun ; 15(1): 2701, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538601

ABSTRACT

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.


Subject(s)
Heart Failure , Myocardial Infarction , Humans , Calgranulin B , Prognosis , Proteomics , Calgranulin A/genetics , Myocardial Infarction/complications , Heart Failure/etiology , Biomarkers , Syndrome
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