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1.
J Appl Toxicol ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38837250

In recent years, semiconductor nanomaterials, as one of the most promising and applied classes of engineered nanomaterials, have been widely used in industries such as photovoltaics, electronic devices, and biomedicine. However, occupational exposure is unavoidable during the production, use, and disposal stages of products containing these materials, thus posing potential health risks to workers. The intricacies of the work environment present challenges in obtaining comprehensive data on such exposure. Consequently, there remains a significant gap in understanding the exposure risks and toxic effects associated with semiconductor nanomaterials. This paper provides an overview of the current classification and applications of typical semiconductor nanomaterials. It also delves into the existing state of occupational exposure, methodologies for exposure assessment, and prevailing occupational exposure limits. Furthermore, relevant epidemiological studies are examined. Subsequently, the review scrutinizes the toxicity of semiconductor nanomaterials concerning target organ toxicity, toxicity mechanisms, and influencing factors. The aim of this review is to lay the groundwork for enhancing the assessment of occupational exposure to semiconductor nanomaterials, optimizing occupational exposure limits, and promoting environmentally sustainable development practices in this domain.

2.
Nanomaterials (Basel) ; 14(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38727330

Lossy mode resonance (LMR) sensors offer a promising avenue to surpass the constraints of conventional surface plasmon resonance (SPR) sensors by delivering enhanced label-free detection capabilities. A notable edge of LMR over SPR is its excitation potential by both transverse electric (TE) and transverse magnetic (TM) polarized light. Yet this merit remains underexplored due to challenges to achieving high sensing performance under both TM and TE polarization within a singular LMR model. This study introduces a theoretical model for an LMR prism refractive index sensor based on a MgF2-few layer black phosphorus-MgF2 configuration, which can achieve angular sensitivity nearing 90° refractive index unit-1 (RIU-1) for both polarizations. Leveraging the distinct anisotropic nature of black phosphorus, the figure of merit (FOM) values along its two principal crystal axes (zigzag and armchair) show great difference, achieving an impressive FOM of 1.178 × 106 RIU-1 along the zigzag direction under TE polarized light and 1.231 × 104 RIU-1 along the armchair direction under TM polarized light. We also provide an analysis of the electric field distribution for each configuration at its respective resonant conditions. The proposed structure paves the way for innovative applications of anisotropic-material-based LMR sensors in various applications.

3.
J Refract Surg ; 40(5): e321-e327, 2024 May.
Article En | MEDLINE | ID: mdl-38717082

PURPOSE: To evaluate the characteristic of corrective epithelial thickness after femtosecond laser-assisted lenticule intrastromal keratoplasty (LIKE) to correct moderate-to-high hyperopia. METHODS: The prospective case series study of the LIKE procedure was performed to correct moderate-to-high hyperopia. The epithelial thickness map was generated by anterior segment optical coherence tomography (AS-OCT) in the corneal central 9-mm zone. Keratometry and corneal higher order aberrations were analyzed by Pentacam (Oculus Optikgeräte GmbH) preoperatively and postoperatively. RESULTS: In the 26 eyes of 13 participants who underwent the LIKE procedure for moderate-to-high hyperopia, the attempted spherical equivalence (SEQ) was +6.50 ± 1.09 diopters (D). Compared to the preoperative epithelial thickness maps, the postoperative epithelial thickness had become significantly thinner in the central 5-mm zone; the difference was 6 to 7 µm. The paracentral epithelium performed nonuniform remodeling; the thinnest epithelial thickness was located in the inferotemporal section, which has the greatest difference from the superonasal; the difference between these two was approximately 3 µm. Through correlation analysis, it was found that the sections with thinner epithelium were significantly related to corneal curvature and corneal vertical coma. CONCLUSIONS: The LIKE procedure can be used to correct moderate-to-high hyperopia. This study further indicated the epithelial remodeling characteristic after the LIKE procedure: the central and paracentral corneal epithelial thickness becomes thinner, and the epithelial thickness distributes non-uniformly, which may be the important factor of the postoperative curvature asymmetric distribution and induction of corneal vertical coma. [J Refract Surg. 2024;40(5):e321-e327.].


Corneal Stroma , Corneal Topography , Epithelium, Corneal , Hyperopia , Refraction, Ocular , Tomography, Optical Coherence , Visual Acuity , Humans , Hyperopia/surgery , Hyperopia/physiopathology , Prospective Studies , Corneal Stroma/surgery , Corneal Stroma/pathology , Male , Female , Adult , Visual Acuity/physiology , Epithelium, Corneal/surgery , Epithelium, Corneal/pathology , Refraction, Ocular/physiology , Middle Aged , Lasers, Excimer/therapeutic use , Young Adult , Corneal Wavefront Aberration/physiopathology , Corneal Surgery, Laser/methods , Eye Diseases, Hereditary
4.
J Chromatogr A ; 1727: 464996, 2024 Jul 19.
Article En | MEDLINE | ID: mdl-38763087

Supermacroporous composite cryogels with enhanced adjustable functionality have received extensive interest in bioseparation, tissue engineering, and drug delivery. However, the variations in their components significantly impactfinal properties. This study presents a two-step hybrid machine learning approach for predicting the properties of innovative poly(2-hydroxyethyl methacrylate)-poly(vinyl alcohol) composite cryogels embedded with bacterial cellulose (pHEMA-PVA-BC) based on their compositions. By considering the ratios of HEMA (1.0-22.0 wt%), PVA (0.2-4.0 wt%), poly(ethylene glycol) diacrylate (1.0-4.5 wt%), BC (0.1-1.5 wt%), and water (68.0-96.0 wt%) as investigational variables, overlay sampling uniform design (OSUD) was employed to construct a high-quality dataset for model development. The random forest (RF) model was used to classify the preparation conditions. Then four models of artificial neural network, RF, gradient boosted regression trees (GBRT), and XGBoost were developed to predict the basic properties of the composite cryogels. The results showed that the RF model achieved an accurate three-class classification of preparation conditions. Among the four models, the GBRT model exhibited the best predictive performance of the basic properties, with the mean absolute percentage error of 16.04 %, 0.85 %, and 2.44 % for permeability, effective porosity, and height of theoretical plate (1.0 cm/min), respectively. Characterization results of the representative pHEMA-PVA-BC composite cryogel showed an effective porosity of 81.01 %, a permeability of 1.20 × 10-12 m2, and a range of height of theoretical plate between 0.40-0.49 cm at flow velocities of 0.5-3.0 cm/min. These indicate that the pHEMA-PVA-BC cryogel was an excellent material with supermacropores, low flow resistance and high mass transfer efficiency. Furthermore, the model output demonstrates that the alteration of the proportions of PVA (0.2-3.5 wt%) and BC (0.1-1.5 wt%) components in composite cryogels resulted in significant changes in the material basic properties. This work represents an attempt to efficiently design and prepare target composite cryogels using machine learning and providing valuable insights for the efficient development of polymers.


Cellulose , Cryogels , Machine Learning , Polyhydroxyethyl Methacrylate , Polyvinyl Alcohol , Cryogels/chemistry , Polyvinyl Alcohol/chemistry , Polyhydroxyethyl Methacrylate/chemistry , Cellulose/chemistry , Porosity , Neural Networks, Computer
5.
CNS Neurosci Ther ; 30(5): e14738, 2024 05.
Article En | MEDLINE | ID: mdl-38702933

INTRODUCTION: Microglia are the main phagocytes in the brain and can induce neuroinflammation. Moreover, they are critical to alpha-synuclein (α-syn) aggregation and propagation. Plasma exosomes derived from patients diagnosed with Parkinson's disease (PD-exo) reportedly evoked α-syn aggregation and inflammation in microglia. In turn, microglia internalized and released exosomal α-syn, enhancing α-syn propagation. However, the specific mechanism through which PD-exo influences α-syn degradation remains unknown. METHODS: Exosomes were extracted from the plasma of patients with PD by differential ultracentrifugation, analyzed using electron microscopy (EM) and nanoparticle flow cytometry, and stereotaxically injected into the unilateral striatum of the mice. Transmission EM was employed to visualize lysosomes and autophagosomes in BV2 cells, and lysosome pH was measured with LysoSensor Yellow/Blue DND-160. Cathepsin B and D, lysosomal-associated membrane protein 1 (LAMP1), ATP6V1G1, tumor susceptibility gene 101 protein, calnexin, α-syn, ionized calcium binding adaptor molecule 1, and NLR family pyrin domain containing 3 were evaluated using quantitative polymerase chain reaction or western blotting, and α-syn, LAMP1, and ATP6V1G1 were also observed by immunofluorescence. Small interfering ribonucleic acid against V1G1 was transfected into BV2 cells and primary microglia using Lipofectamine® 3000. A PD mouse model was established via injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into mice. A lentiviral-mediated strategy to overexpress ATP6V1G1 in the brain of MPTP-treated mice was employed. Motor coordination was assessed using rotarod and pole tests, and neurodegeneration in the mouse substantia nigra and striatum tissues was determined using immunofluorescence histochemical and western blotting of tyrosine hydroxylase. RESULTS: PD-exo decreased the expression of V1G1, responsible for the acidification of intra- and extracellular milieu. This impairment of lysosomal acidification resulted in the accumulation of abnormally swollen lysosomes and decreased lysosomal enzyme activities, impairing lysosomal protein degradation and causing α-syn accumulation. Additionally, V1G1 overexpression conferred the mice neuroprotection during MPTP exposure. CONCLUSION: Pathogenic protein accumulation is a key feature of PD, and compromised V-type ATPase dysfunction might participate in PD pathogenesis. Moreover, V1G1 overexpression protects against neuronal toxicity in an MPTP-based PD mouse model, which may provide opportunities to develop novel therapeutic interventions for PD treatment.


Exosomes , Mice, Inbred C57BL , Microglia , Parkinson Disease , Vacuolar Proton-Translocating ATPases , alpha-Synuclein , Aged , Animals , Female , Humans , Male , Mice , Middle Aged , alpha-Synuclein/metabolism , Exosomes/metabolism , Lysosomes/metabolism , Microglia/metabolism , Microglia/pathology , Parkinson Disease/metabolism , Parkinson Disease/pathology , Vacuolar Proton-Translocating ATPases/metabolism , Vacuolar Proton-Translocating ATPases/genetics
6.
ACS Nano ; 18(21): 13818-13828, 2024 May 28.
Article En | MEDLINE | ID: mdl-38748457

Ion transport efficiency, the key to determining the cycling stability and rate capability of all-solid-state lithium metal batteries (ASSLMBs), is constrained by ionic conductivity and Li+-migration ability across the multicomponent phases and interfaces in ASSLMBs. Here, we report a robust strategy for the large-scale fabrication of a practical solid electrolyte composite with high-throughput linear Li+-transport channels by compositing an all-trans block copolymer PVDF-b-PTFE matrix with ferroelectric BaTiO3-TiO2 nanofiber films. The electrolyte shows a sustainable electromechanical-coupled deformability that enables the rapid dissociation of anions with Li+ to create more movable Li+ ions and spontaneously transform the battery internal strain into Li+-ion migration kinetic energy. The ceramic framework homogenizes the interfacial potential with electrodes, endowing the electrolyte with a high conductivity of 0.782 mS·cm-1 and stable ion transport ability in ASSLMBs at room temperature. The batteries of LiFePO4/Li can stably cycle 1000 times at 0.5 C with a high capacity retention of 96.1%, and Ah-grade pouch or high-voltage Li(Ni0.8Mn0.1Co0.1)O2/Li batteries also exhibit excellent rate capability and cycling performance.

7.
Adv Mater ; : e2400745, 2024 May 29.
Article En | MEDLINE | ID: mdl-38810961

The development of scalable and passive coatings that can adapt to seasonal temperature changes while maintaining superhydrophobic self-cleaning functions is crucial for their practical applications. However, the incorporation of passive cooling and heating functions with conflicting optical properties in a superhydrophobic coating is still challenging. Herein, an all-in-one coating inspired by the hierarchical structure of a lotus leaf that combines surface wettability, optical structure, and temperature self-adaptation is obtained through a simple one-step phase separation process. This coating exhibits an asymmetrical gradient structure with surface-embedded hydrophobic SiO2 particles and subsurface thermochromic microcapsules within vertically distributed hierarchical porous structures. Moreover, the coating imparts superhydrophobicity, high infrared emission, and thermo-switchable sunlight reflectivity, enabling autonomous transitions between radiative cooling and solar warming. The all-in-one coating prevents contamination and over-cooling caused by traditional radiative cooling materials, opening up new prospects for the large-scale manufacturing of intelligent thermoregulatory coatings.

8.
Nat Commun ; 15(1): 4590, 2024 May 30.
Article En | MEDLINE | ID: mdl-38816360

Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation. Intriguingly, we find that pharmacological inhibition of FLI1 effectively obstructs the CBP/STAT1-IDO1-Kyn axis, thereby invigorating both spontaneous and checkpoint therapy-induced immune responses, culminating in enhanced tumor eradication. In conclusion, our findings delineate FLI1-mediated Kyn metabolism as an immune evasion mechanism in NPC, furnishing valuable insights into potential therapeutic interventions.


Indoleamine-Pyrrole 2,3,-Dioxygenase , Interferon-gamma , Kynurenine , Proto-Oncogene Protein c-fli-1 , STAT1 Transcription Factor , T-Lymphocytes, Regulatory , Tumor Microenvironment , Kynurenine/metabolism , Interferon-gamma/metabolism , Interferon-gamma/immunology , Animals , Proto-Oncogene Protein c-fli-1/metabolism , Proto-Oncogene Protein c-fli-1/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects , Humans , Mice , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , STAT1 Transcription Factor/metabolism , Cell Line, Tumor , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/drug therapy , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/drug effects , Mice, Inbred C57BL , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Tumor Escape/drug effects , Mice, Knockout
9.
Front Microbiol ; 15: 1341512, 2024.
Article En | MEDLINE | ID: mdl-38572234

Introduction: Gut microbiota are closely related to the nutrition, immunity, and metabolism of the host and play important roles in maintaining the normal physiological activities of animals. Cranes are important protected avian species in China, and they are sensitive to changes in the ecological environment and are thus good environmental indicators. There have been no reports examining gut fungi or the correlation between bacteria and fungi in wild Demoiselle cranes (Grus virgo) and Common cranes (Grus grus). Related research can provide a foundation for the protection of rare wild animals. Methods: 16S rRNA and ITS high-throughput sequencing techniques were used to analyze the gut bacterial and fungal diversity of Common and Demoiselle cranes migrating to the Yellow River wetland in Inner Mongolia. Results: The results revealed that for gut bacteria α diversity, Chao1 index in Demoiselle cranes was remarkably higher than that in Common cranes (411.07 ± 79.54 vs. 294.92 ± 22.38), while other index had no remarkably differences. There was no remarkable difference in fungal diversity. There were marked differences in the gut microbial composition between the two crane species. At the phylum level, the highest abundance of bacteria in the Common crane and Demoiselle crane samples was Firmicutes, accounting for 87.84% and 74.29%, respectively. The highest abundance of fungi in the guts of the Common and Demoiselle cranes was Ascomycota, accounting for 69.42% and 57.63%, respectively. At the genus level, the most abundant bacterial genus in the Common crane sample was Turicibacter (38.60%), and the most abundant bacterial genus in the Demoiselle crane sample was Catelicoccus (39.18%). The most abundant fungi in the Common crane sample was Penicillium (6.97%), and the most abundant fungi in the Demoiselle crane sample was Saccharomyces (8.59%). Correlation analysis indicated that there was a significant correlation between gut bacteria and fungi. Discussion: This study provided a research basis for the protection of cranes. Indeed, a better understanding of the gut microbiota is very important for the conservation and management of wild birds, as it not only helps us to understand their life history and related mechanisms, but also can hinder the spread of pathogenic microorganisms.

10.
J Ethnopharmacol ; 330: 118223, 2024 Aug 10.
Article En | MEDLINE | ID: mdl-38642624

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.


Apoptosis , Cerebral Hemorrhage , Leonurus , Molecular Docking Simulation , Network Pharmacology , Neurons , Animals , Apoptosis/drug effects , Leonurus/chemistry , Neurons/drug effects , Neurons/metabolism , Mice , Male , Cerebral Hemorrhage/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Janus Kinase 1/metabolism , STAT1 Transcription Factor/metabolism , Disease Models, Animal
11.
J Environ Manage ; 357: 120773, 2024 Apr.
Article En | MEDLINE | ID: mdl-38555845

Extraction of coastline from optical remote sensing images is of paramount importance for coastal zone management, erosion monitoring, and intelligent ocean construction. However, nearshore marine environment complexity presents a challenge when capturing small-scale and detailed information regarding coastlines. Furthermore, the presence of numerous tidal flats, suspended sediments, and coastal biological communities exacerbates the reduction in segmentation accuracy, which is particularly noticeable in medium-high-resolution remote sensing image segmentation tasks. Most previous related studies, based primarily on convolutional neural networks (CNNs) or traditional feature extraction methods, faced challenges in detailed pixel-level refinement and lacked comprehensive understanding of the studied images. Therefore, we proposed a new U-shaped deep learning model (STIRUnet) that combines the excellent global modeling ability of SwinTransformer with an improved CNN using an inverted residual module. The proposed method has the capability of global supervised feature learning and layer-by-layer feature extraction, and we conducted sea-land segmentation experiments using GF-HNCD and BSD remote sensing image datasets to validate the performance of the proposed model. The results indicate the following: 1) suspended sediments and coastal biological communities are major contributors to coastline blurring, and 2) the recovery of minute features (e.g., narrow watercourses and microscale artificial structures) effectively enhances edge details and leads to more realistic segmentation outcomes. The findings of this study are highly important in relation of accurate extraction of sea-land information in complex marine environments, and they offer novel insights regarding mixed-pixel identification.


Biota , Neural Networks, Computer , Telemetry , Image Processing, Computer-Assisted
12.
Phys Chem Chem Phys ; 26(13): 10243-10253, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38497485

Cubic nanoparticles of CeO2 were partly covered on the tetrahedron surface of γ-Bi2O3 through a hydrothermal reaction and then a calcination process to construct a novel S-type γ-Bi2O3/CeO2 heterojunction. The optimized sample removed 96% of lomefloxacin and 81% of tetracycline. During the cycling test, the photocatalytic efficiency of lomefloxacin and tetracycline was maintained above 87% and 80%, respectively, for five consecutive cycles. According to XRD and Raman spectra characterization, the sample after cycling held a stable crystal structure. Holes, OH-˙, O2˙, and electrons participated in the degradation of lomefloxacin, while tetracycline was removed via the effect of the former three active substances. Based on theoretical calculation and experimental tests, the excellent photocatalytic activity of γ-Bi2O3/CeO2 came from the fast transfer of charge carriers along the S-type path. Moreover, the CB electrons of γ-Bi2O3 and VB holes of CeO2 were preserved to generate free radicals for antibiotic degradation. The colony numbers of Escherichia coli were 1.50 × 10-6 CFU mL-1 and 1.39 × 10-6 CFU mL-1 in solutions after the degradation of the two pollutants, which represents the non-toxicity of the final products. The γ-Bi2O3/CeO2 sample has a potential application for antibiotic removal from modern sewage.


Anti-Bacterial Agents , Environmental Pollutants , Tetracycline , Electrons , Escherichia coli
13.
ACS Appl Mater Interfaces ; 16(11): 13858-13868, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38441545

Large volume strain and slow kinetics are the main obstacles to the application of high-specific-capacity alloy-type metal tellurides in potassium-ion storage systems. Herein, Bi2Te3-x nanocrystals with abundant Te-vacancies embedded in nitrogen-doped porous carbon nanofibers (Bi2Te3-x@NPCNFs) are proposed to address these challenges. In particular, a hierarchical porous fiber structure can be achieved by the polyvinylpyrrolidone-etching method and is conducive to increasing the Te-vacancy concentration. The unique porous structure together with defect engineering modulates the potassium storage mechanism of Bi2Te3, suppresses structural distortion, and accelerates K+ diffusion capacity. The meticulously designed Bi2Te3-x@NPCNFs electrode exhibits ultrastable cycling stability (over 3500 stable cycles at 1.0 A g-1 with a capacity degradation of only 0.01% per cycle) and outstanding rate capability (109.5 mAh g-1 at 2.0 A g-1). Furthermore, the systematic ex situ characterization confirms that the Bi2Te3-x@NPCNFs electrode undergoes an "intercalation-conversion-step alloying" mechanism for potassium storage. Kinetic analysis and density functional theory calculations reveal the excellent pseudocapacitive performance, attractive K+ adsorption, and fast K+ diffusion ability of the Bi2Te3-x@NPCNFs electrode, which is essential for fast potassium-ion storage. Impressively, the assembled Bi2Te3-x@NPCNFs//activated-carbon potassium-ion hybrid capacitors achieve considerable energy/power density (energy density up to 112 Wh kg-1 at a power density of 1000 W kg-1) and excellent cycling stability (1600 cycles at 10.0 A g-1), indicating their potential practical applications.

14.
Exp Neurol ; 376: 114757, 2024 Jun.
Article En | MEDLINE | ID: mdl-38508481

The intricate functional interactions between mitochondria and lysosomes play a pivotal role in maintaining cellular homeostasis and proper cellular functions. This dynamic interplay involves the exchange of molecules and signaling, impacting cellular metabolism, mitophagy, organellar dynamics, and cellular responses to stress. Dysregulation of these processes has been implicated in various neurodegenerative diseases. Additionally, mitochondrial-lysosomal crosstalk regulates the exosome release in neurons and glial cells. Under stress conditions, neurons and glial cells exhibit mitochondrial dysfunction and a fragmented network, which further leads to lysosomal dysfunction, thereby inhibiting autophagic flux and enhancing exosome release. This comprehensive review synthesizes current knowledge on mitochondrial regulation of cell death, organelle dynamics, and vesicle trafficking, emphasizing their significant contributions to neurodegenerative diseases. Furthermore, we explore the emerging field of nanomedicine in the management of neurodegenerative diseases. The review provides readers with an insightful overview of nano strategies that are currently advancing the mitochondrial-lysosome-extracellular vesicle axis as a therapeutic approach for mitigating neurodegenerative diseases.


Extracellular Vesicles , Lysosomes , Mitochondria , Neurodegenerative Diseases , Humans , Lysosomes/metabolism , Extracellular Vesicles/metabolism , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Mitochondria/metabolism , Animals , Theranostic Nanomedicine/methods
16.
Br J Pharmacol ; 181(12): 1768-1792, 2024 Jun.
Article En | MEDLINE | ID: mdl-38355288

BACKGROUND AND PURPOSE: Panax ginseng is widely applied in the adjuvant treatment of cardiometabolic diseases in clinical practice without clear mechanisms. This study aims to clearly define the efficacy and underlying mechanism of P. ginseng and its active components in protecting against atherosclerosis. EXPERIMENTAL APPROACH: The anti-atherogenic efficacy of total ginseng saponin extract (TGS) and its components was evaluated on Ldlr-/- mice. Gut microbial structure was analysed by 16S rRNA sequencing and PCR. Bile acid profiles were revealed using targeted metabolomics with LC-MS/MS analysis. The contribution of gut microbiota to atherosclerosis was assessed by co-housing experiments. KEY RESULTS: Ginsenoside Rb1, representing protopanaxadiol (PPD)-type saponins, increased intestinal Lactobacillus abundance, resulting in enhanced bile salt hydrolase (BSH) activity to promote intestinal conjugated bile acid hydrolysis and excretion, followed by suppression of enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signal, and thereby increased cholesterol 7α-hydroxylase (CYP7A1) transcriptional expression and facilitated metabolic elimination of cholesterol. Synergistically, protopanaxatriol (PPT)-type saponins, represented by ginsenoside Rg1, protected against atherogenesis-triggered gut leak and metabolic endotoxaemia. Ginsenoside Rg1 directly induced mucin production to nutritionally maintain Akkermansia muciniphila, which reciprocally inhibited gut permeation. Rb1/Rg1 combination, rather than a single compound, can largely mimic the holistic efficacy of TGS in protecting Ldlr-/- mice from atherogenesis. CONCLUSION AND IMPLICATIONS: Our study provides strong evidence supporting TGS and ginsenoside Rb1/Rg1 combinations as effective therapies against atherogenesis, via targeting different signal nodes by different components and may provide some elucidation of the holistic mode of herbal medicines.


Atherosclerosis , Gastrointestinal Microbiome , Ginsenosides , Homeostasis , Mice, Knockout , Panax , Animals , Ginsenosides/pharmacology , Gastrointestinal Microbiome/drug effects , Homeostasis/drug effects , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Male , Mice , Panax/chemistry , Mice, Inbred C57BL , Bile Acids and Salts/metabolism , Receptors, LDL/metabolism , Fibroblast Growth Factors/metabolism , Amidohydrolases/metabolism , Cholesterol 7-alpha-Hydroxylase/metabolism
17.
Redox Biol ; 70: 103063, 2024 Apr.
Article En | MEDLINE | ID: mdl-38316067

Vascular diseases, a leading cause of death in human, are strongly associated with pathological damage to blood vessels. The selenoprotein (Sel) have been reported to play important roles in vascular disease. However, the role of SelO in vascular disease has not been conclusively investigated. The present experiment was to investigate the regulatory mechanism of the effect of SelO on the permeability of vascular endothelial. The H.E staining, FITC-Dextran staining, Dil-AC-LDL staining and FITC-WGA staining showed that vascular structure was damaged, and intercellular junctions were disrupted with selenium (Se)-deficient. Immunohistochemistry, qPCR and Western blot revealed decreased expression of the adhesion plaque proteins vinculin, talin and paxillin, decreased expression of the vascular connectivity effector molecules connexin, claudin-1 and E-cadherin and increased expression of JAM-A and N-cadherin, as well as decreased expression of the ZO-1 signaling pathways ZO-1, Rock, rhoGEF, cingulin and MLC-2. In a screening of 24 Sel present in mice, SelO showed the most pronounced changes in vascular tissues, and a possible association between SelO and vascular intercellular junction effectors was determined using IBM SPSS Statistics 25. Silencing of SelO, vascular endothelial intercellular junction adverse effects present. The regulatory relationship between SelO and vascular endothelial intercellular junctions was determined. The results showed that Se deficiency lead to increased vascular endothelial permeability and vascular tissue damage by decreasing SelO expression, suggesting a possible role for SelO in regulating vascular endothelial permeability.


Selenium , Vascular Diseases , Humans , Animals , Mice , Endothelial Cells/metabolism , Selenium/metabolism , Vascular Diseases/pathology , Permeability , Selenoproteins/genetics , Selenoproteins/metabolism
18.
Ageing Res Rev ; 95: 102232, 2024 Mar.
Article En | MEDLINE | ID: mdl-38364915

Circadian rhythms are involved in the regulation of many aspects of the body, including cell function, physical activity and disease. Circadian disturbance often predates the typical symptoms of neurodegenerative diseases and is not only a non-motor symptom, but also one of the causes of their occurrence and progression. Glial cells possess circadian clocks that regulate their function to maintain brain development and homeostasis. Emerging evidence suggests that the microglial circadian clock is involved in the regulation of many physiological processes, such as cytokine release, phagocytosis, and nutritional and metabolic support, and that disruption of the microglia clock may affect multiple aspects of Parkinson's disease, especially neuroinflammation and α-synuclein processes. Herein, we review recent advances in the circadian control of microglia function in health and disease, and discuss novel pharmacological interventions for microglial clocks in neurodegenerative disorders.


Circadian Clocks , Neurodegenerative Diseases , Parkinson Disease , Humans , Parkinson Disease/metabolism , Microglia/metabolism , Neurodegenerative Diseases/metabolism , Circadian Rhythm/physiology
19.
BMJ Open ; 14(2): e079659, 2024 02 05.
Article En | MEDLINE | ID: mdl-38316584

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) presents a serious cardiovascular condition requiring prompt intervention. Dysglycaemia has been identified as a significant risk factor impacting STEMI prognosis. However, limited research has focused on comprehensively examining the association between glucose dynamics during the perioperative period and patient outcomes. This study aims to address this gap by leveraging continuous glucose monitoring (CGM) technology to gain real-time insights into glucose fluctuations and their potential impact on STEMI prognosis. METHODS AND ANALYSIS: This is a multicentre, prospective, 3-year follow-up cohort study. Between May 2023 and May 2024, 550 eligible STEM patients who underwent percutaneous coronary intervention are expected to be recruited. Using the CGM system, continuous glucose levels will be collected throughout the perioperative phase. Key clinical parameters, including cardiac biomarkers, angiographic findings and major adverse cardiovascular events, will be assessed in relation to glucose profile. ETHICS AND DISSEMINATION: The study was approved by the Medical Research Ethics Committee of The First Affiliated Hospital of University of Science and Technology of China and will be conducted in accordance with the moral, ethical and scientific principles of the Declaration of Helsinki. Written informed consent will be obtained from all participants before any study-related procedures are implemented. Study results will be disseminated through conferences and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2300069662.


Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/surgery , Cohort Studies , Follow-Up Studies , Glucose , Blood Glucose , Prospective Studies , Blood Glucose Self-Monitoring , Continuous Glucose Monitoring , Prognosis , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome
20.
Small ; : e2306483, 2024 Jan 17.
Article En | MEDLINE | ID: mdl-38229561

As a highly promising nanomaterial, exploring the impact of the liver, a vital organ, stands out as a crucial focus in the examination of its biological effects. Kupffer cells (KCs) are one of the first immune cells to contact with exotic-substances in liver. Therefore, this study investigates the immunomodulatory effects and mechanisms of polyethylene glycol-modified graphene oxide (GO-PEG) on KCs. Initial RNA-seq and KEGG pathway analyses reveal the inhibition of the TOLL-like receptor, TNF-α and NOD-like receptor pathways in continually stimulated KCs exposed to GO-PEG. Subsequent biological experiments validate that a 48-hour exposure to GO-PEG alleviates LPS-induced KCs immune activation, characterized by a shift in polarization from M1 to M2. The underlying mechanism involves the absorption of double-stranded RNA/single-stranded RNA, inhibiting the activation of TLR3 and TLR7 in KCs. Employing a Kupffer/AML12 cell co-culture model and animal studies, it is observed that GO-PEG indirectly inhibit oxidative stress, mitochondrial dysfunction, and apoptosis in AML12 cells, partially mitigating systemic inflammation and preserving liver tissue/function. This effect is attributed to the paracrine interaction between KCs and hepatocytes. These findings suggest a meaningful and effective strategy for treating liver inflammation, particularly when combined with anti-inflammatory drugs.

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