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1.
Environ Res ; : 119792, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39142455

ABSTRACT

The functionality of activated sludge in wastewater treatment processes depends largely on the structural and microbial composition of its flocs, which are complex assemblages of microorganisms and their secretions. However, monitoring these flocs in real-time and consistently has been challenging due to the lack of suitable technologies and analytical methods. Here we present a laboratory setup capable of capturing instantaneous microscopic images of activated sludge, along with algorithms to interpret these images. To improve floc identification, an advanced Mask R-CNN-based segmentation that integrates a Dual Attention Network (DANet) with an enhanced Feature Pyramid Network (FPN) was used to enhance feature extraction and segmentation accuracy. Additionally, our novel PointRend module meticulously refines the contours of boundaries, significantly minimising pixel inaccuracies. Impressively, our approach achieved a floc detection accuracy of >95%. This development marks a significant advancement in real-time sludge monitoring, offering essential insights for optimising wastewater treatment operations proactively.

2.
Physiol Rep ; 12(15): e16179, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39107084

ABSTRACT

Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high-density lipoprotein (rHDL) ameliorated renal injury in eNOS-/- dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non-diabetes), eNOS-/- dbdb (diabetes), and eNOS-/- dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS-/- dbdb mice at Week 16 at 5 µg/g body weight in ~100 µL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS-/- dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.


Subject(s)
Diabetic Nephropathies , Lipoproteins, HDL , Mice, Inbred C57BL , Nitric Oxide Synthase Type III , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/pathology , Mice , Male , Nitric Oxide Synthase Type III/metabolism , Lipoproteins, HDL/pharmacology , Female , Mice, Knockout , Kidney/pathology , Kidney/metabolism , Kidney/drug effects , Albuminuria , Fibronectins/metabolism , Fibronectins/genetics , Fibrosis , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy
3.
Materials (Basel) ; 17(15)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39124402

ABSTRACT

In the paper, the eccentric compression behavior of the truss-reinforced cross-shaped concrete-filled steel tubular (CCFST) column is investigated. A total of eighteen CCFST columns were tested under eccentric compression, and the key test variables included the reinforced truss node spacing (s = 140 mm and 200 mm), slenderness ratio (λ = 9.2, 16.6, and 23.1), and eccentricity ratio (η = 0, 0.08, and 0.15). The failure mode, deformation characteristic, stress distribution, strain distribution at the mid-span of the steel tube, and the eccentric compression bearing capacity were assessed. The results show that due to the addition of reinforced truss, the steel plates near the mid-span of eccentrically compressed CCFST columns experienced multi-wave buckling rather than single-wave buckling after the peak load was reduced to 85%, and the failure mode of concrete also changed from single-section to multi-section collapse failure. Comparisons were made with the unstiffened specimen. The ductility coefficient of the stiffened specimen with eccentricity ratios of 0.08-0.15 and node spacings of 140 mm~200 mm increased by 70~83%, approaching that of the multi-cell specimens with an increasing steel ratio of 1.8%. In addition, by comparing the test results with the calculation results of four domestic and international design codes, it was found that the Chinese codes CECS159-2018 and GB50936-2014, and the Eurocode 4 (2004) can be better employed to predict the compression bearing capacity of truss-reinforced CCFST columns.

4.
Phys Rev Lett ; 133(6): 060801, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39178437

ABSTRACT

Bosonic loss estimation has an important role in quantum metrology. It was once believed that the ultimate precision of this task is restricted to the standard quantum limit if no quantum probe is involved. Nevertheless, a recent proposal showed that this limit can be surpassed by utilizing ring resonators with coherent state probe. Here, we experimentally realize the resonator-based bosonic loss estimation and verify the resonant enhancement effect. This Letter explores the advantages of resonator-based metrology and sheds light on the development of high-precision miniature sensors.

5.
Eur Spine J ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39168893

ABSTRACT

PURPOSE: Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. METHODS: 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. RESULTS: After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. CONCLUSION: The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.

6.
BMC Psychiatry ; 24(1): 583, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192231

ABSTRACT

BACKGROUND: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . METHODS: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. RESULTS: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant. CONCLUSIONS: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality.


Subject(s)
COVID-19 , Depression , Sleep Quality , Students , Suicidal Ideation , Humans , COVID-19/psychology , COVID-19/epidemiology , Students/psychology , Female , Male , China/epidemiology , Depression/psychology , Depression/epidemiology , Young Adult , Universities , Adult , Adolescent , Circadian Rhythm/physiology , Surveys and Questionnaires , Prevalence , Chronotype
7.
Phytochemistry ; : 114259, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39186996

ABSTRACT

A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.

8.
Langmuir ; 40(32): 16846-16854, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39094224

ABSTRACT

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

9.
ACS Appl Mater Interfaces ; 16(31): 41518-41533, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39046307

ABSTRACT

Dental caries, one of the most prevalent infectious diseases, is the primary contributor to the early loss of natural teeth and is a significant public health issue. Known as the tooth's bioactive core, the dentin-pulp complex (DPCX) comprises tightly connected hard and soft tissues that not only serve as a biological barrier for the inner tooth tissue but also produce reparative dentin following mild disruptions. While efforts to preserve DPCX are numerous, most strategies focus on temporary antibacterial measures, inflammation reduction, or tissue regeneration, lacking a comprehensive, long-lasting solution. In this study, TVH-19, an autoadaptive peptide mimicking the pH- and ion-responsive capacity of amelogenin, was designed to exert multifaceted preservation of DPCX, providing a comprehensive strategy for preserving vital pulp. Leveraging its unique amphiphilicity-related cell penetration and ion/pH-responsive self-assembly properties, TVH-19 outperforms conventional pulp preservation materials by being capable of rapid cell penetration, minimizing diffused side effects, providing environment-responsive self-assembly/disassembly for balanced long-term antibacterial and cell protection, and facilitating the formation of lysosomal-escaping intracellular aggregates for the continuous activation of PDGFRα+ dental pulp stem cells.


Subject(s)
Amelogenin , Dental Caries , Dental Pulp , Dentin , Dental Pulp/drug effects , Dental Caries/prevention & control , Dentin/chemistry , Dentin/drug effects , Amelogenin/chemistry , Animals , Humans , Peptides/chemistry , Peptides/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hydrogen-Ion Concentration , Mice
10.
Int J Biol Macromol ; 276(Pt 1): 133647, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38964693

ABSTRACT

Teeth discoloration poses a widespread challenge in dental health across various regions. Conventional teeth whitening methods often result in enamel deterioration and soft tissue harm due to the utilization of incompatible whitening agents and continuous intense light exposure. Here, we propose an effective phototherapy technique for teeth whitening, employing pathways of energy transition through intersystem crossing. The integration of MoS2 nanosheets into carrageenan gel (MoS2 NSs@Carr) facilitates both photothermal-hyperthermia and the generation of reactive oxygen species (ROS) through photocatalytic processes. The efficacy of ROS generation by the phototherapeutic MoS2 NSs@Carr on teeth whitening in the scenario. This approach ensures comprehensive teeth whitening by eliminating deep-seated stains on the teeth while preserving structural integrity and avoiding any tissue toxicity. This research highlights the efficacy of the phototherapeutic MoS2 NSs@Carr for dental whitening and underscores the potential of exploring nanostructures based on MoS2 NSs for managing dental healthcare issue.


Subject(s)
Carrageenan , Disulfides , Hydrogels , Molybdenum , Tooth Bleaching , Molybdenum/chemistry , Disulfides/chemistry , Tooth Bleaching/methods , Hydrogels/chemistry , Carrageenan/chemistry , Humans , Reactive Oxygen Species/metabolism , Animals , Dental Care , Phototherapy/methods , Nanostructures/chemistry
11.
Apoptosis ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39044092

ABSTRACT

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

12.
Planta ; 260(2): 50, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990341

ABSTRACT

MAIN CONCLUSION: BcERF98 is induced by ethylene signaling and inhibits the expression of BcFT by interacting with BcNF-YA2 and BcEIP9, thereby inhibiting plant flowering. Several stresses trigger the accumulation of ethylene, which then transmits the signal to ethylene response factors (ERFs) to participate in the regulation of plant development to adapt to the environment. This study clarifies the function of BcERF98, a homolog of AtERF98, in the regulation of plant flowering time mediated by high concentrations of ethylene. Results indicate that BcERF98 is a nuclear and the cell membrane-localized transcription factor and highly responsive to ethylene signaling. BcERF98 inhibits the expression of BcFT by interacting with BcEIP9 and BcNF-YA2, which are related to flowering time regulation, thereby participating in ethylene-mediated plant late flowering regulation. The results have enriched the theoretical knowledge of flowering regulation in non-heading Chinese cabbage (NHCC), providing the scientific basis and gene reserves for cultivating new varieties of NHCC with different flowering times.


Subject(s)
Ethylenes , Flowers , Gene Expression Regulation, Plant , Plant Proteins , Transcription Factors , Flowers/genetics , Flowers/physiology , Flowers/growth & development , Ethylenes/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Brassica/genetics , Brassica/physiology , Brassica/metabolism , Brassica/growth & development , Signal Transduction , Plant Growth Regulators/metabolism
13.
Opt Lett ; 49(14): 3982-3985, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008758

ABSTRACT

Ultraviolet and color imaging require different image sensors and optical channels, which results in large size, complex structure, and high cost of imaging systems. Here, we report a novel, to the best of our knowledge, image sensor that combines ultraviolet and color imaging functions. The fabrication of this image sensor is achieved by coating high-transparency CsPbBr3 perovskite nanocrystals in a polymer film on the color filter layer of a silicon-based detector. The film, serving as an ultraviolet photoluminescent layer, exhibits high transparency, exceeding 91.5% at wavelengths beyond the photoluminescence peak of 513 nm. During ultraviolet imaging, the film converts ultraviolet light into visible light, which passes through the green filter layer to reach the detector for imaging. During visible light imaging, red light, green light, and most of the blue light pass through the CsPbBr3 perovskite nanocrystal film and color filter layer to reach the detector for imaging. As a result, the image sensor can capture both 257 nm solar-blind ultraviolet images and color photos in the visible light.

14.
Saudi Pharm J ; 32(7): 102124, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38933713

ABSTRACT

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

15.
Curr Med Chem ; 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38831674

ABSTRACT

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

16.
J Colloid Interface Sci ; 672: 97-106, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38833738

ABSTRACT

Formate is an important environmental pollutant, and meanwhile its concentration change is associated with a variety of diseases. Thus, rapid and sensitive detection of formate is critical for the biochemical analysis of complex samples and clinical diagnosis of multiple diseases. Herein, a colorimetric biosensor was constructed based on the cascade catalysis of formate oxidase (FOx) and horseradish peroxidase (HRP). These two enzymes were co-immobilized in Cu3(PO4)2-based hybrid nanoflower with spatial localization, in which FOx and HRP were located in the shell and core of nanoflower, respectively (FOx@HRP). In this system, FOx could catalyze the oxidation of formate to generate H2O2, which was then utilized by HRP to oxidize 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid to yield blue product. Ideal linear correlation could be obtained between the absorbance at 420 nm and formate concentration. Meanwhile, FOx@HRP exhibited excellent detection performance with low limit of detection (6 µM), wide linear detection range (10-900 µM), and favorable specificity, stability and reusability. Moreover, it could be applied in the detection of formate in environmental, food and biological samples with high accuracy. Collectively, FOx@HRP provides a useful strategy for the simple and sensitive detection of formate and is potentially to be used in biochemical analysis and clinical diagnosis.


Subject(s)
Colorimetry , Enzymes, Immobilized , Formates , Horseradish Peroxidase , Colorimetry/methods , Formates/chemistry , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Biosensing Techniques/methods , Limit of Detection , Nanostructures/chemistry , Particle Size , Surface Properties
17.
Nat Commun ; 15(1): 5469, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937477

ABSTRACT

Porous frameworks constructed via noncovalent interactions show wide potential in molecular separation and gas adsorption. However, it remains a major challenge to prepare these materials from low-symmetry molecular building blocks. Herein, we report a facile strategy to fabricate noncovalent porous crystals through modular self-assembly of a low-symmetry helicene racemate. The P and M enantiomers in the racemate first stack into right- and left-handed triangular prisms, respectively, and subsequently the two types of prisms alternatively stack together into a hexagonal network with one-dimensional channels with a diameter of 14.5 Å. Remarkably, the framework reveals high stability upon heating to 275 °C, majorly due to the abundant π-interactions between the complementarily engaged helicene building blocks. Such porous framework can be readily prepared by fast rotary evaporation, and is easy to recycle and repeatedly reform. The refined porous structure and enriched π-conjugation also favor the selective adsorption of a series of small molecules.

18.
Adv Sci (Weinh) ; 11(31): e2309940, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38874114

ABSTRACT

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.


Subject(s)
Liver Cirrhosis , Needles , Animals , Liver Cirrhosis/therapy , Mice , Disease Models, Animal , Humans , Male , Cell-Free System
19.
Free Radic Biol Med ; 222: 361-370, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38945456

ABSTRACT

BACKGROUND: To date, Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disease associated with clinical complications. Dietary fatty acids have been suggested to be involved in preventing or reversing the accumulation of hepatic fat. However, contradicting roles of monounsaturated fatty acids to the liver have been implicated in various human and murine models, mainly due to the insolubility nature of fatty acids. METHODS: High pressure homogenization methods were used to fabricate oleic acid embedded lipid nanoparticles (OALNs). The in vitro and in vivo models were used to validate the physiological effect of this OALNs via various cellular and molecular approaches including cell viability essay, fluorescent staining, electron microscope, RNAseq, qPCR, Western blots, and IHC staining. RESULTS: We successfully fabricated OALNs with enhanced stability and solubility. More importantly, lipid accumulation was successfully induced in hepatocytes via the application of OALNs in a dose-dependent manner. Overload of OALNs resulted in ROS accumulation and apoptosis of hepatocytes dose-dependently. With the help of transcriptome sequencing and traditional experimental approaches, we demonstrated that the lipotoxic effect induced by OALNs was exerted via the DDIT3/BCL2/BAX/Caspases signaling. Moreover, we also verified that OALNs induced steatosis and subsequent apoptosis in the liver of mice via the activation of DDIT3 in vivo. CONCLUSIONS: In all, our results established a potential pathogenic model of NAFLD for further studies and indicated the possible involvement of DDIT3 signaling in abnormal steatosis process of the liver.


Subject(s)
Apoptosis , Hepatocytes , Nanoparticles , Non-alcoholic Fatty Liver Disease , Oleic Acid , Reactive Oxygen Species , Signal Transduction , Transcription Factor CHOP , Animals , Hepatocytes/metabolism , Hepatocytes/pathology , Hepatocytes/drug effects , Nanoparticles/chemistry , Mice , Humans , Oleic Acid/chemistry , Reactive Oxygen Species/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/chemically induced , Apoptosis/drug effects , Signal Transduction/drug effects , Transcription Factor CHOP/metabolism , Transcription Factor CHOP/genetics , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Male , Hep G2 Cells , Liposomes
20.
Biomaterials ; 311: 122645, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38850717

ABSTRACT

Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.


Subject(s)
Heterocyclic Compounds, 3-Ring , Immunotherapy , Membrane Proteins , Printing, Three-Dimensional , Proto-Oncogene Proteins c-akt , Animals , Membrane Proteins/agonists , Membrane Proteins/metabolism , Immunotherapy/methods , Proto-Oncogene Proteins c-akt/metabolism , Heterocyclic Compounds, 3-Ring/pharmacology , Mice , Tissue Scaffolds/chemistry , Cell Line, Tumor , Mice, Inbred C57BL , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/immunology , Humans , Female , Mice, Inbred BALB C
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