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1.
Int J Biol Macromol ; 269(Pt 2): 132089, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705331

RESUMO

Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy.

2.
Food Chem ; 450: 138961, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38640544

RESUMO

The detection of tetracycline antibiotics (TCs) in food holds great significance in minimizing their absorption within the human body. Hence, this study aims to develop a rapid, convenient, real-time, and accurate detection method for detecting antibiotics in an authentic market setting. A colorimetric fluorescence sensor was devised for tetracycline detection utilizing PVA aerogels as the substrate. Its operating principle is based on the IFE effect and antenna effect. A detection device is designed to capture fluorescence images while deep learning was employed to aid in the detection process. The sensor exhibits high responsiveness with a mere 60-s requirement for detection and demonstrates substantial color changes(blue to red), achieving 99% accuracy within the range of 10-100 µM with the assistance of deep learning (Resnet18). Real sample simulation tests yielded recovery rates between 95% and 130%. Overall, the proposed strategy proved to be a simple, portable, reliable, and responsive solution for rapid real-time TCs detection in food samples.

3.
J Nanobiotechnology ; 22(1): 201, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659058

RESUMO

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.


Assuntos
Micropartículas Derivadas de Células , Células Dendríticas , Inflamação , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Animais , Camundongos , Inflamação/tratamento farmacológico , Micropartículas Derivadas de Células/metabolismo , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Vesículas Extracelulares , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Sepse/imunologia , Sepse/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Humanos , Imunoterapia/métodos
4.
J Nanobiotechnology ; 22(1): 103, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468261

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.


Assuntos
Artrite Reumatoide , Cério , Compostos de Manganês , Nanopartículas , Óxidos , Humanos , Manganês/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Inflamação , Cério/farmacologia
5.
Carbohydr Polym ; 330: 121821, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368102

RESUMO

Restoration of the lubrication functions of articular cartilage is an effective treatment to alleviate the progression of osteoarthritis (OA). Herein, we fabricated chitosan-block-poly(sulfobetaine methacrylate) (CS-b-pSBMA) copolymer via a free radical polymerization of sulfobetaine methacrylate onto activated chitosan segment, structurally mimicking the lubricating biomolecules on cartilage. The successful copolymerization of CS-b-pSBMA was verified by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and 1H nuclear magnetic resonance. Friction test confirmed that the CS-b-pSBMA copolymer could achieve an excellent lubrication effect on artificial joint materials such as Ti6Al4V alloy with a coefficient of friction as low as 0.008, and on OA-simulated cartilage, better than the conventional lubricant hyaluronic acid, and the adsorption effect of lubricant on cartilage surface was proved by a fluorescence labeling experiment. In addition, CS-b-pSBMA lubricant possessed an outstanding stability, which can withstand enzymatic degradation and even a long-term storage up to 4 weeks. In vitro studies showed that CS-b-pSBMA lubricant had a favorable antibacterial activity and good biocompatibility. In vivo studies confirmed that the CS-b-pSBMA lubricant was stable and could alleviate the degradation process of cartilage in OA mice. This biomimetic lubricant is a promising articular joint lubricant for the treatment of OA and cartilage restoration.


Assuntos
Cartilagem Articular , Quitosana , Osteoartrite , Animais , Camundongos , Quitosana/farmacologia , Lubrificantes , Biomimética , Lubrificação , Polímeros/farmacologia
6.
Environ Toxicol ; 39(5): 3055-3148, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38319140

RESUMO

BACKGROUND: This study aimed to type breast cancer in relation to reactive oxygen species (ROS), clinical indicators, single nucleotide variant (SNV) mutations, functional differences, immune infiltration, and predictive responses to immunotherapy or chemotherapy, and constructing a prognostic model. METHODS: We used uniCox analysis, ConsensusClusterPlus, and the proportion of ambiguous clustering (PAC) to analyze The Cancer Genome Atlas (TCGA) data to determine optimal groupings and obtain differentially expressed ROS-related genes. Clinical indicators were then combined with the classification results and the Chi-square test was used to assess differences. We further examined SNV mutations, and functional differences using gene set enrichment analysis (GSEA) analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, immune cell infiltration, and response to immunotherapy and chemotherapy. A prognostic model for breast cancer was constructed using these differentially expressed genes, immunotherapy or chemotherapy responses, and survival curves. RT-qPCR was used to detect the differences in the expression of LCE3D, CA1, PIRT and SMR3A in breast cancer cell lines and normal breast epithelial cell line. RESULTS: We identified two distinct tumor types with significant differences in ROS-related gene expression, clinical indicators, SNV mutations, functional pathways, and immune infiltration. The response to specific chemotherapy drugs and immunotherapy treatments also documented significant differences. The prognostic model constructed with 16 genes linked to survival could efficiently divide patients into high- and low-risk groups. The high-risk group showed a poorer prognosis, higher tumor purity, distinct immune microenvironment, and lower immunotherapy response. RT-qPCR results showed that LCE3D, CA1, PIRT and SMR3A are highly expressed in breast cancer. CONCLUSION: Our methodical examination presented an enhanced insight into the molecular and immunological heterogeneity of breast cancer. It can contribute to the understanding of prognosis and offer valuable insights for personalized treatment strategies. Further, the prognostic model can potentially serve as a powerful tool for risk stratification and therapeutic decision-making in clinical settings.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Espécies Reativas de Oxigênio , Prognóstico , Células MCF-7 , Microambiente Tumoral/genética
7.
Macromol Rapid Commun ; 45(8): e2300643, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38225681

RESUMO

Smart hydrogels responsive to external stimuli are promising for various applications such as soft robotics and smart devices. High mechanical strength and fast response rate are particularly important for the construction of hydrogel actuators. Herein, tough hydrogels with rapid response rates are synthesized using vinyl-functionalized poly(N-isopropylacrylamide) (PNIPAM) microgels as macro-crosslinkers and N-isopropylacrylamide as monomers. The compression strength of the obtained PNIPAM hydrogels is up to 7.13 MPa. The response rate of the microgel-crosslinked hydrogels is significantly enhanced compared with conventional chemically crosslinked PNIPAM hydrogels. The mechanical strength and response rate of hydrogels can be adjusted by varying the proportion of monomers and crosslinkers. The lower critical solution temperature (LCST) of the PNIPAM hydrogels could be tuned by copolymerizing with ionic monomer sodium methacrylate. Thermo-responsive bilayer hydrogels are fabricated using PINPAM hydrogels with different LCSTs via a layer-by-layer method. The thermo-responsive fast swelling and shrinking properties of the two layers endow the bilayer hydrogel with anisotropic structures and asymmetric response characteristics, allowing the hydrogel to respond rapidly. The bilayer hydrogels are fabricated into clamps to grab small objects and flowers that mimicked the closure of petals, and it shows great application prospects in the field of actuators.


Assuntos
Resinas Acrílicas , Hidrogéis , Temperatura , Hidrogéis/química , Hidrogéis/síntese química , Resinas Acrílicas/química , Microgéis/química , Reagentes de Ligações Cruzadas/química , Acrilamidas/química
8.
Clin Exp Optom ; 107(1): 58-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37078165

RESUMO

CLINICAL RELEVANCE: Anisometropia can affect visual development in children. Investigations of anisometropia in high myopes would explore potential causes related to anisometropia, highlighting the management of anisometropia in high myopia. BACKGROUND: The prevalence of anisometropia ranged from 0.6% to 4.3% in general paediatric population and from 7% to 14% in myopes. Anisometropia is regarded as an associated factor for myopia development, while myopia progression is a stimulus driving anisometropic development. The purpose of this study was to investigate the prevalence of anisometropia and its association with refraction development in Chinese children with high myopia. METHODS: In the cohort study, a total of 1,577 highly myopic (spherical equivalent ≤-5.0D) children aged 4-18 years were included. Refractive parameters (dioptre of sphere, dioptre of cylinder, corneal curvature radius, and axial length) of both eyes were measured after cycloplegia. The prevalence and degree of anisometropia were compared among refractive groups (non-parametric tests or chi-square tests), and regression analyses were used to determine associated factors of anisometropia. The statistical significance was set to P < 0.05 (two-tailed). RESULTS: In highly myopic children with a mean (standard deviation) age of 13.06 (2.80) years, the proportions of spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia ≥1.00 D were 34.5%, 21.9% and 39.9%, respectively. There was more spherical equivalent anisometropia associated with more severe astigmatism (P for trend <0.001). In the multivariate regression analysis, more spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia were associated with higher degrees of astigmatism (standard beta = -0.175, -0.148 and -0.191, respectively). More spherical anisometropia was associated with better spherical power (standard beta = 0.116). CONCLUSION: The proportion of anisometropia in highly myopic children was high, compared with previously reported general population, and more severe anisometropia was associated with higher degree of cylindrical power, but not spherical power.


Assuntos
Anisometropia , Astigmatismo , Miopia , Humanos , Criança , Anisometropia/epidemiologia , Anisometropia/complicações , Estudos de Coortes , Refração Ocular , Miopia/epidemiologia , Comprimento Axial do Olho
9.
Eye (Lond) ; 38(3): 606-613, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37770533

RESUMO

OBJECTIVES: To characterize choroidal vascular changes in children with different refractive status. METHODS: A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm. RESULTS: The mean ChT and CVI were 275.88 ± 53.34 µm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 µm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05). CONCLUSIONS: In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development.


Assuntos
Hiperopia , Macula Lutea , Miopia , Criança , Humanos , Fóvea Central , Refração Ocular , Corioide/irrigação sanguínea , Tomografia de Coerência Óptica/métodos
10.
Small ; 20(16): e2304318, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38018305

RESUMO

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.


Assuntos
Hidrogéis , Traumatismos da Medula Espinal , Humanos , Camundongos , Animais , Hidrogéis/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Neurônios/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/uso terapêutico
11.
Bioengineering (Basel) ; 10(11)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38002420

RESUMO

For patients eligible to undergo breast-conserving surgery (BCS) after neoadjuvant chemotherapy, accurate preoperative localisation of tumours is vital to ensure adequate tumour resection that can reduce recurrence probability effectively. For this reason, we have developed a 3D-printed personalised breast surgery guide (BSG) assisted with supine magnetic resonance imaging (MRI) and image 3D reconstruction technology, capable of mapping the tumour area identified on MRI onto the breast directly using dual positioning based on the manubrium and nipple. In addition, the BSG allows the colour dye to be injected into the breast to mark the tumour region to be removed, yielding more accurate intraoperative resection and satisfactory cosmetic outcomes. The device has been applied to 14 patients from January 2018 to July 2023, with two positive margins revealed by the intraoperative biopsy. This study showed that the BSG-based method could facilitate precise tumour resection of BCS by accurately localising tumour extent and margin, promoting the clinical efficacy in patients with breast cancer as well as simplifying the surgical process.

12.
Nat Cancer ; 4(9): 1309-1325, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37550516

RESUMO

To avoid regulatory T cell promotion and vascular toxicity, the interleukin-2 receptor-ß/interleukin-2 receptor-γ (IL-2Rßγ)-biased approach is used by most IL-2 analogs in immuno-oncology. However, recent clinical disappointments in these IL-2 agonists have questioned this strategy. Here we show that both wild-type (IL-2wt) and IL-2Rßγ-attenuated (IL-2α-bias) agonists that preserve IL-2Rα (CD25) activities can effectively expand tumor-specific CD8+ T cells (TSTs) and exhibit better antitumor efficacy and safety than the 'non-α' counterpart (IL-2nα). Mechanistically, TSTs coexpress elevated CD25 and PD-1 and are more susceptible to stimulation by IL-2Rα-proficient agonists. Moreover, the antitumor efficacy of anti-PD-1 depends on activation of PD-1+CD25+ TSTs through autocrine IL-2-CD25 signaling. In individuals with cancer, a low IL-2 signature correlates with non-responsiveness to anti-PD-1 treatment. In mouse models, IL-2α-bias, but not IL-2nα, restores the IL-2 signature and synergizes with anti-PD-1 to eradicate large established tumors. These findings underscore the indispensable function of CD25 in IL-2-based immunotherapy and provide rationales for evaluating IL-2Rα-biased agonists in individuals with cancer.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Camundongos , Animais , Subunidade alfa de Receptor de Interleucina-2 , Linfócitos T CD8-Positivos/patologia , Interleucina-2/farmacologia , Receptor de Morte Celular Programada 1 , Neoplasias/tratamento farmacológico
13.
J Physiol ; 601(17): 3905-3920, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37431690

RESUMO

Kinesin family member 2C (KIF2C)/mitotic centromere-associated kinesin (MCAK), is thought to be oncogenic as it is involved in tumour progression and metastasis. Moreover, it also plays a part in neurodegenerative conditions like Alzheimer's disease and psychiatric disorders such as suicidal schizophrenia. Our previous study conducted on mice demonstrated that KIF2C is widely distributed in various regions of the brain, and is localized in synaptic spines. Additionally, it regulates microtubule dynamic properties through its own microtubule depolymerization activity, thereby affecting AMPA receptor transport and cognitive behaviour in mice. In this study, we show that KIF2C regulates the transport of mGlu1 receptors in Purkinje cells by binding to Rab8. KIF2C deficiency in Purkinje cells results in abnormal gait, reduced balance ability and motor incoordination in male mice. These data suggest that KIF2C is essential for maintaining normal transport and synaptic function of mGlu1 and motor coordination in mice. KEY POINTS: KIF2C is localized in synaptic spines of hippocampus neurons, and regulates excitatory transmission, synaptic plasticity and cognitive behaviour. KIF2C is extensively expressed in the cerebellum, and we investigated its functions in development and synaptic transmission of cerebellar Purkinje cells. KIF2C deficiency in Purkinje cells alters the expression of metabotropic glutamate receptor 1 (mGlu1) and the AMPA receptor GluA2 subunit at Purkinje cell synapses, and changes excitatory synaptic transmission, but not inhibitory transmission. KIF2C regulates the transport of mGlu1 receptors in Purkinje cells by binding to Rab8. KIF2C deficiency in Purkinje cells affects motor coordination, but not social behaviour in male mice.


Assuntos
Células de Purkinje , Receptores de Glutamato Metabotrópico , Masculino , Animais , Camundongos , Células de Purkinje/fisiologia , Receptores de AMPA/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Cerebelo/metabolismo , Proteínas de Transporte/metabolismo , Sinapses/metabolismo , Proteínas de Ciclo Celular/metabolismo
14.
Br J Ophthalmol ; 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37290823

RESUMO

AIMS: To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. METHODS: This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. RESULTS: In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. CONCLUSION: A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. TRIAL REGISTRATION NUMBER: NCT03666052.

15.
Int J Biol Macromol ; 243: 125249, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295698

RESUMO

Trauma-induced articular cartilage damages are common in clinical practice. Hydrogels have been used to fill the cartilage defects and act as extracellular matrices for cell migration and tissue regeneration. Lubrication and stability of the filler materials are essential to achieve a satisfying healing effect in cartilage regeneration. However, conventional hydrogels failed to provide a lubricous effect, or could not anchor to the wound to maintain a stable curing effect. Herein, we fabricated dually cross-linked hydrogels using oxidized hyaluronic acid (OHA) and N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) methacrylate (HTCCMA). The OHA/HTCCMA hydrogels, which were dynamically cross-linked and then covalently cross-linked by photo-irradiation, showed appropriate rheological properties and self-healing capability. The hydrogels exhibited moderate and stable tissue adhesion property due to formation of dynamic covalent bonds with the cartilage surface. The coefficient of friction values were 0.065 and 0.078 for the dynamically cross-linked and double-cross-linked hydrogels, respectively, demonstrating superior lubrication. In vitro studies showed that the hydrogels had good antibacterial ability and promoted cell proliferation. In vivo studies confirmed that the hydrogels were biocompatible and biodegradable, and exhibited a robust regenerating ability for articular cartilage. This lubricant-adhesive hydrogel is expected to be promising for the treatment of joint injuries as well as regeneration.


Assuntos
Cartilagem Articular , Quitosana , Cartilagem Articular/metabolismo , Hidrogéis/química , Ácido Hialurônico/farmacologia , Ácido Hialurônico/química , Quitosana/farmacologia , Adesivos , Lubrificantes
16.
Materials (Basel) ; 16(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37374644

RESUMO

Among the various ceramic substrate materials, Si3N4 ceramics have demonstrated high thermal conductivity, good thermal shock resistance, and excellent corrosion resistance. As a result, they are well-suited for semiconductor substrates in high-power and harsh conditions encountered in automobiles, high-speed rail, aerospace, and wind power. In this work, Si3N4 ceramics with various ratios of α-Si3N4 and ß-Si3N4 in raw powder form were prepared by spark plasma sintering (SPS) at 1650 °C for 30 min under 30 MPa. When the content of ß-Si3N4 was lower than 20%, with the increase in ß-Si3N4 content, the ceramic grain size changed gradually from 1.5 µm to 1 µm and finally resulted in 2 µm mixed grains. However, As the content of ß-Si3N4 seed crystal increased from 20% to 50%, with the increase in ß-Si3N4 content, the ceramic grain size changed gradually from 1 µm and 2 µm to 1.5 µm. Therefore, when the content of ß-Si3N4 in the raw powder is 20%, the sintered ceramics exhibited a double-peak structure distribution and the best overall performance with a density of 97.5%, fracture toughness of 12.1 MPa·m1/2, and a Vickers hardness of 14.5 GPa. The results of this study are expected to provide a new way of studying the fracture toughness of silicon nitride ceramic substrates.

18.
Materials (Basel) ; 16(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37241297

RESUMO

A novel energy-absorbing structure, the Koch hierarchical honeycomb, which combines the Koch geometry with a conventional honeycomb structure, is proposed in this work. Adopting a hierarchical design concept using Koch has improved the novel structure more than the honeycomb. The mechanical properties of this novel structure under impact loading are studied by finite element simulation and compared with the conventional honeycomb structure. To effectively verify the reliability of the simulation analysis, quasi-static compression experiments were conducted on 3D-printed specimens. The results of the study showed that the first-order Koch hierarchical honeycomb structure increased the specific energy absorption by 27.52% compared to the conventional honeycomb structure. Furthermore, the highest specific energy absorption can be obtained by increasing the hierarchical order to 2. Moreover, the energy absorption of triangular and square hierarchies can be significantly increased. All achievements in this study provide significant guidelines in the reinforcement design of lightweight structures.

19.
Adv Sci (Weinh) ; 10(15): e2204592, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37017573

RESUMO

As major regulators on bone formation/resorption in response to mechanical stimuli, osteocytes have shown great promise for restoring bone injury. However, due to the unmanageable and unabiding cell functions in unloading or diseased environments, the efficacy of osteogenic induction by osteocytes has been enormously limited. Herein, a facile method of oscillating fluid flow (OFF) loading for cell culture is reported, which enables osteocytes to initiate only osteogenesis and not the osteolysis process. After OFF loading, multiple and sufficient soluble mediators are produced in osteocytes, and the collected osteocyte lysates invariably induce robust osteoblastic differentiation and proliferation while restraining osteoclast generation and activity under unloading or pathological conditions. Mechanistic studies confirm that elevated glycolysis and activation of the ERK1/2 and Wnt/ß-catenin pathways are the major contributors to the initiation of osteoinduction functions induced by osteocytes. Moreover, an osteocyte lysate-based hydrogel is designed to establish a stockpile of "active osteocytes" to sustainably deliver bioactive proteins, resulting in accelerated healing through regulation of endogenous osteoblast/osteoclast homeostasis.


Assuntos
Reabsorção Óssea , Osteoclastos , Humanos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteócitos/metabolismo , Hidrogéis/metabolismo , Osteoblastos/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Homeostase
20.
Nutrients ; 15(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36839205

RESUMO

Here, the aim was to evaluate the protective effect of Lactobacillus plantarum-derived postbiotics, i.e., LP-cs, on acute alcoholic liver injury (ALI). After preincubation with LP-cs, HL7702 human hepatocytes were treated with alcohol, and then the cell survival rate was measured. C57BL/6 male mice were presupplemented with or without LP-cs and LP-cs-loaded calcium alginate hydrogel (LP-cs-Gel) for 3 weeks and given 50% alcohol gavage to establish the mouse model of ALI, LP-cs presupplementation, and LP-cs-Gel presupplementation. The histomorphology of the liver and intestines; the levels of serum AST, ALT, lipid, and SOD activity; liver transcriptomics; and the metagenome of intestinal microbiota were detected in all mouse models. In vitro, LP-cs significantly increased the survival rate of alcohol-treated cells. In vivo, presupplementation with LP-cs and LP-cs-Gel restored the levels of serum AST, ALT, and SOD activity, as well as TC and TG, after acute alcohol intake. In the LP-cs-presupplemented mice, the genes involved in fatty acid metabolic processes were upregulated and the genes involved in steroid biosynthesis were downregulated significantly as compared with the ALI mice. LP-cs significantly increased the abundance of intestinal microbiota, especially Akkermansia muciniphila. In conclusion, LP-cs ameliorates ALI by protecting hepatocytes against oxidative damage, thereby, improving lipid metabolism and regulating the intestinal microbiota. The effect of LP-cs-Gel is similar to that of LP-cs.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Lactobacillus plantarum , Masculino , Humanos , Animais , Camundongos , Lactobacillus plantarum/fisiologia , Metabolismo dos Lipídeos , Microbioma Gastrointestinal/fisiologia , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Etanol/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
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