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1.
Nanoscale ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949653

ABSTRACT

Possessing excellent electronic properties and high chemical stability, semiconducting n-type two-dimensional (2D) tin dioxide (SnO2) nanosheets have been featured in sensing and electrocatalysis applications recently. Derived from non-layered crystal structures, 2D SnO2 has abundant unsaturated dangling bonds existing at the surface, providing interfacial activity. How the surface chemistry alters the electronic properties of 2D SnO2 nanomaterials remains unexplored. In this study, we synthesised ultra-thin 2D SnO2 nanosheets using a liquid metal (LM) touch printing technique and investigated experimentally and theoretically how the interactions of organic solvents composed of alkyl and hydroxyl groups with the surface of LM-derived 2D SnO2 modulate the electronic properties. It was found that alkane solvents can physically absorb onto the SnO2 surface with no impact on the material conductivity. Alcohol-based solvents on the other hand interact with the SnO2 surface via chemical absorptions primarily, in which oxygen atoms of hydroxyl groups in the alcohols form bonds with the surface atoms of SnO2. The binding stability is determined by the length and configuration of the hydrocarbon chain in alcohols. As representative long-chain alcohols, 1-octanol and 1-pentanol attach onto the SnO2 surface strongly, lowering the binding energy of Sn4+ and reducing the electron transfer ability of SnO2 nanosheets. Consequently, the electronic properties, i.e. conductivity and electronic mobility of SnO2 nanosheet-based electronic devices are decreased significantly.

2.
Nat Commun ; 15(1): 5538, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956032

ABSTRACT

The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.


Subject(s)
Cryoelectron Microscopy , Deep Learning , Protein Conformation , Proteins , Cryoelectron Microscopy/methods , Proteins/chemistry , Molecular Dynamics Simulation , Neural Networks, Computer , Databases, Protein , Computational Biology/methods
3.
J Hazard Mater ; 474: 134786, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38824778

ABSTRACT

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure.


Subject(s)
Endothelial Cells , Fibroblasts , Lung , Pulmonary Fibrosis , Volatile Organic Compounds , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Volatile Organic Compounds/toxicity , Lung/drug effects , Lung/pathology , Intercellular Signaling Peptides and Proteins/metabolism , Mice , Axl Receptor Tyrosine Kinase , Mice, Inbred C57BL , Air Pollution, Indoor/adverse effects , Male , Signal Transduction/drug effects
5.
Materials (Basel) ; 17(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38893891

ABSTRACT

Hydraulic asphalt concrete is known for its excellent seepage control performance and strong deformation resistance. This engineering material has widespread applications in the seepage control structures of hydraulic buildings. Recent projects have investigated the use of acidic aggregates to improve economic efficiency. However, they have also highlighted the weaker adhesion between acidic aggregates and asphalt, which necessitates stringent construction process control. This study investigates the impact of resting conditions on the tensile properties of acidic aggregate hydraulic asphalt concrete. The results of the tensile testing indicate that the storage time significantly affects the performance of asphalt concrete. The tensile strength of the specimens without anti-stripping agents decreased from 1.711 MPa to 0.914 MPa after resting periods of 0, 10, 20, and 30 days. The specimens treated with anti-stripping agents also showed a decrease in tensile strength over time, similar to the trend observed in the previous specimens. Digital specimen simulations indicated a decrease in cohesion between the asphalt and the aggregate from 5.375 MPa to 2.664 MPa after 30 days, representing a reduction of 50.44%. To counteract the effect of the storage time on the bonding between acidic aggregates and asphalt, this study recommends reducing the grading index and maximum size of aggregates, decreasing the coarse aggregate content, and selecting smooth aggregate shapes.

7.
Poult Sci ; 103(8): 103938, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38908123

ABSTRACT

The aim of this study was to examine the effects of NH3 variations across different positions within a cage-reared duck house on the egg production performance and fecal microbiome in Muscovy ducks. Totals of 3,168 female Muscovy ducks (180 ± 2 d) were randomly assigned to 1,056 cages. From d 293 to 300, the egg production rate and levels of NH3, H2S, CO2, temperature, humidity, light intensity, and dust particles were recorded. Two spatial distribution-based experimental classification methods were applied, one grouping ducks into Front, Middle, and End categories, and the other into First, Second, and Third layers. On d 300, serum and feces samples were collected for further analysis. The result showed that both the egg production rate and serum PROG level in the Front were higher than End (P < 0.05). However, no significant differences were found among the First, Second, and Third groups. Among the environmental factors, ammonia (NH3) is a major harmful gas in cage-reared duck houses, with observed concentrations showing a gradient from lower levels in the Front group to higher levels in the Middle group (P < 0.05), and even higher levels in the End group (P < 0.05). Gene sequencing of the 16S rRNA gene revealed a higher relative abundance of Firmicutes in both the Front and Middle groups compared to the End group (P < 0.05). Specifically, within the Firmicutes phylum, the relative abundance of Lactobacillus and Romboutsia was notably higher in the Front group compared to both the Middle and End groups (P < 0.05). What's more, the abundance of Lactobacillus had a negative correlation with NH3 concentration and positive correlation with egg production rate. In conclusion, NH3 concentrations showed variations across different areas of the cage-reared duck house, with higher levels detected at the rear. The elevated NH3 level was identified as the main factor negatively impacting egg production in Muscovy ducks and contributing to a decline in the abundance of Firmicutes, specifically Lactobacillus.

8.
Sci Total Environ ; 934: 173254, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38761924

ABSTRACT

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.


Subject(s)
Air Pollutants , Sleep Wake Disorders , Volatile Organic Compounds , Animals , Mice , Air Pollutants/toxicity , Sleep Wake Disorders/chemically induced , Neuroinflammatory Diseases/chemically induced , Air Pollution, Indoor/adverse effects , Male , Signal Transduction/drug effects , Glutamic Acid/metabolism
9.
Support Care Cancer ; 32(6): 370, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776028

ABSTRACT

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.


Subject(s)
Biomarkers, Tumor , Creatinine , Cytokines , Immune Checkpoint Inhibitors , Neoplasms , Humans , Male , Female , Neoplasms/drug therapy , Neoplasms/blood , Middle Aged , Aged , Cytokines/blood , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Creatinine/blood , Biomarkers, Tumor/blood , Adult , Aged, 80 and over , B7-H1 Antigen/blood , Case-Control Studies
10.
Heliyon ; 10(7): e28873, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596132

ABSTRACT

Objective: In the RECO study, we investigated the impact of the operator's choice of stent retriever size on patients with internal carotid artery (ICA) occlusion. Methods: Data from the RECO Registry, a prospective multicentre study, were utilized. Patients who underwent mechanical thrombectomy (MT) were divided according to the size of the stent into the RECO 4 × 20 group, the RECO 5 × 30 group and the RECO 6 × 30 group. The outcome measures assessed in the study were the 3-month modified Rankin Scale (mRS) score, occurrence of any intracranial haemorrhage (aICH), workflow timing, recanalization success rate, number of attempts, and all-cause mortality within a 3-month period. Results: Analysis was conducted on a total of 89 patients with ICA occlusion. RECO 4 × 20, 5 × 30, and 6 × 30 stent retrievers were used in 19 (21.3%), 52 (58.4%), and 18 (20.2%) patients, respectively. The demographic and baseline characteristics showed considerable similarity across the three groups. The puncture-to-recanalization time of the RECO 6 × 30 group [56.5 min (IQR, 41.5-80.8)] was significantly shorter than that of the RECO 4 × 20 group [110 min (IQR, 47-135)]. In 10 out of 18 patients (55.6%), the RECO 6 × 30 stent retriever achieved reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score 2b-3) after the initial attempt, surpassing the rates of 31.6% in the RECO 4 × 20 group and 32.7% in the RECO 5 × 30 group. In the RECO 4 × 20 group, the median number of passes was 2 (IQR, 1-3); in the RECO 5 × 30 group, it was 2 (IQR, 1-3); and in the RECO 6 × 30 groups, it was 1 (IQR, 1-2.5). There were no statistically significant differences observed among the three groups concerning aICH or good outcomes (mRS score 0-2). Conclusion: Our study demonstrated the practical implications of stent-retriever size selection in the context of the MT for ICA occlusion. The routine use of a RECO 6 × 30 stent retriever holds the potential for early revascularization in clinical practice. The significant reduction in the puncture-to-reperfusion time and the greater first-pass effect associated with this stent size underscore its efficiency in treating ICA occlusion.

11.
Neurol Genet ; 10(2): e200132, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38586597

ABSTRACT

Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC. However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC-related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID.

13.
CNS Neurosci Ther ; 30(4): e14685, 2024 04.
Article in English | MEDLINE | ID: mdl-38634270

ABSTRACT

OBJECTIVE: Neuronal precursor cells expressed developmentally down-regulated 4 (Nedd4) are believed to play a critical role in promoting the degradation of substrate proteins and are involved in numerous biological processes. However, the role of Nedd4 in intracerebral hemorrhage (ICH) remains unknown. This study aims to investigate the regulatory role of Nedd4 in the ICH model. METHODS: Male C57BL/6J mice were induced with ICH. Subsequently, the levels of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, as well as the expression of divalent metal transporter 1 (DMT1) and Nedd4 were assessed after ICH. Furthermore, the impact of Nedd4 overexpression was evaluated through analyses of hematoma area, ferroptosis, and neurobehavioral function. The mechanism underlying Nedd4-mediated degradation of DMT1 was elecidated using immunoprecipitation (IP) after ICH. RESULTS: Upon ICH, the level of DMT1 in the brain increased, but decreased when Nedd4 was overexpressed using Lentivirus, suggesting a negative correlation between Nedd4 and DMT1. Additionally, the degradation of DMT1 was inhibited after ICH. Furthermore, it was found that Nedd4 can interact with and ubiquitinate DMT1 at lysine residues 6, 69, and 277, facilitating the degradation of DMT1. Functional analysis indicated that overexpression of Nedd4 can alleviate ferroptosis and promote recovery following ICH. CONCLUSION: The results demonstrated that ferroptosis occurs via the Nedd4/DMT1 pathway during ICH, suggesting it potential as a valuable target to inhibit ferroptosis for the treatment of ICH.


Subject(s)
Cation Transport Proteins , Cerebral Hemorrhage , Ferroptosis , Nedd4 Ubiquitin Protein Ligases , Animals , Male , Mice , Brain/metabolism , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/pathology , Ferroptosis/genetics , Mice, Inbred C57BL , Ubiquitination , Nedd4 Ubiquitin Protein Ligases/metabolism , Cation Transport Proteins/metabolism
14.
Childs Nerv Syst ; 40(7): 2227-2233, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38635072

ABSTRACT

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.


Subject(s)
Fibroma, Desmoplastic , Skull Neoplasms , beta Catenin , Humans , Male , beta Catenin/genetics , Child, Preschool , Fibroma, Desmoplastic/genetics , Fibroma, Desmoplastic/surgery , Fibroma, Desmoplastic/pathology , Fibroma, Desmoplastic/diagnostic imaging , Skull Neoplasms/genetics , Skull Neoplasms/surgery , Skull Neoplasms/diagnostic imaging , Skull Neoplasms/pathology , Mutation , Tomography, X-Ray Computed
15.
Int J Biol Macromol ; 266(Pt 1): 131058, 2024 May.
Article in English | MEDLINE | ID: mdl-38522707

ABSTRACT

Long-term exposure to inhalable silica particles may lead to severe systemic pulmonary disease, such as silicosis. Exosomes have been demonstrated to dominate the pathogenesis of silicosis, but the underlying mechanisms remain unclear. Therefore, this study aimed to explore the roles of exosomes by transmitting miR-107, which has been linked to the toxic pulmonary effects of silica particles. We found that miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in exosomes extracted from the serum of patients with silicosis. Notably, an increase in miR-107 in serum exosomes and lung tissue was observed in the experimental silicosis mouse model, while the inhibition of miR-107 reduced pulmonary fibrosis. Moreover, exosomes helped the migration of miR-107 from macrophages to lung fibroblasts, triggering the transdifferentiation of cell phenotypes. Further experiments demonstrated that miR-107 targets CDK6 and suppresses the expression of retinoblastoma protein phosphorylation and E2F1, resulting in cell-cycle arrest. Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets.


Subject(s)
Exosomes , MicroRNAs , Pulmonary Fibrosis , Silicon Dioxide , Exosomes/metabolism , Exosomes/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Silicon Dioxide/toxicity , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/pathology , Mice , Humans , Silicosis/metabolism , Silicosis/pathology , Silicosis/genetics , Silicosis/etiology , Cell Communication , Male , Disease Models, Animal , Fibroblasts/metabolism , Macrophages/metabolism , Lung/pathology , Lung/metabolism
16.
Arch Toxicol ; 98(6): 1629-1643, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38536500

ABSTRACT

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.


Subject(s)
Nanoparticles , Organelles , Pulmonary Fibrosis , Soot , Soot/toxicity , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Humans , Nanoparticles/toxicity , Organelles/drug effects , Organelles/metabolism , Animals , Particle Size , Inhalation Exposure/adverse effects , Lung/drug effects , Lung/pathology
17.
J Clin Invest ; 134(6)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38488001

ABSTRACT

Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of oxidative stress in BCSCs remains unclear. We recently found that the histone reader ZMYND8 was upregulated in BCSCs. Here, we showed that ZMYND8 reduced ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high (ALDHhi) BCSCs, leading to BCSC expansion and tumor initiation in mice. The underlying mechanism involved a two-fold posttranslational regulation of nuclear factor erythroid 2-related factor 2 (NRF2). ZMYND8 increased stability of NRF2 protein through KEAP1 silencing. On the other hand, ZMYND8 interacted with and recruited NRF2 to the promoters of antioxidant genes to enhance gene transcription in mammospheres. NRF2 phenocopied ZMYND8 to enhance BCSC stemness and tumor initiation by inhibiting ROS and ferroptosis. Loss of NRF2 counteracted ZMYND8's effects on antioxidant genes and ROS in mammospheres. Interestingly, ZMYND8 expression was directly controlled by NRF2 in mammospheres. Collectively, these findings uncover a positive feedback loop that amplifies the antioxidant defense mechanism sustaining BCSC survival and stemness.


Subject(s)
Breast Neoplasms , Ferroptosis , NF-E2-Related Factor 2 , Neoplastic Stem Cells , Trans-Activators , Animals , Mice , Antioxidants , Ferroptosis/genetics , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Trans-Activators/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology
18.
Heliyon ; 10(6): e27953, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38545178

ABSTRACT

Background and objectives: The neutrophil-to-lymphocyte ratio (NLR) is a widely recognized marker of inflammation in peripheral blood. However, its specific role in neuronal intranuclear inclusion disease (NIID) has not been reported. This study aims to investigate the relationship between NIID and NLR. Methods: A multicenter database was collected, including 157 NIID patients from seven hospitals (The Affiliated Hospital of Xuzhou Medical University, Yantai Yuhuangding Hospital, Tengzhou Central People's Hospital,The Affiliated Brain Hospital of Nanjing Medical University, Liaocheng People's Hospital,The Second Hospital of Shandong University, Inner Mongolia People's Hospital, Xuanwu Hospital Capital Medical University,The First Affiliated Hospital of USTC), along with 157 age- and gender-matched healthy control subjects. White blood cell counts (including neutrophils, lymphocytes, monocytes, eosinophils, and basophils) were obtained, and the NLR was calculated. Additionally, cognitive impairment was assessed using clinical evaluation scores. Results: NIID patients exhibited significantly higher NLR values compared to the healthy control group (p < 0.001). The plasma NLR levels in NIID patients showed a weak positive correlation with disease duration (r = 0.219, p = 0.016). However, no significant correlations were found between NLR and age of onset or cognitive impairment (p > 0.05). Conclusion: There is a significant association between NLR and NIID, suggesting a potential role of peripheral blood inflammation in the pathogenesis of NIID.

19.
Knee Surg Sports Traumatol Arthrosc ; 32(5): 1207-1215, 2024 May.
Article in English | MEDLINE | ID: mdl-38529701

ABSTRACT

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.


Subject(s)
Patellar Dislocation , Tibia , Humans , Female , Male , Adolescent , Child , Tibia/anatomy & histology , Sex Factors , Age Factors , Posterior Cruciate Ligament/anatomy & histology , Reference Values , ROC Curve , Recurrence
20.
Front Microbiol ; 15: 1335017, 2024.
Article in English | MEDLINE | ID: mdl-38404601

ABSTRACT

The gut microbiota of wild animals, influenced by various factors including diet, nutrition, gender, and age, plays a critical role in their health and disease status. This study focuses on raccoon dogs (Nyctereutes procyonoides), a commonly found wild animal, and its gut microbiota composition in response to dietary shifts. The study aimed to compare the fecal bacterial communities and diversity of rescued raccoon dogs fed three different diet types (fish and amphibians, mixed protein with maize, and solely maize) using high-throughput sequencing. Results indicated that the dietary composition significantly influenced the gut microbiota, with notable differences in the abundance of several key phyla and genera. The study identified Firmicutes as the dominant phylum in all diet groups, with notable variations in the relative abundances of Bacteroidota, Proteobacteria, and Verrucomicrobiota. Notably, the group solely fed maize exhibited a significant increase in Proteobacteria, potentially linked to dietary fiber and lignin degradation. The genus-level analysis highlighted significant differences, with Lactobacillus and Bifidobacterium responding to dietary shifts. The genus Akkermansia in Verrucomicrobiota can be identified as a marker for assessing the health of the gut and deserves further investigation. Gender-specific differences in the gut microbiota were observed, highlighting the influence of individual variation. Furthermore, the analysis of bacterial functions suggested a connection between diet and host metabolism, emphasizing the need for further research to understand the complex mechanisms underlying the relationship between dietary composition and gut microbiota in wild animals. These findings provide crucial insights into conservation and rescue efforts for wild animals.

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