•A tumor immunotherapy strategy was developed by the combination of biomimetic nanoparticles and in situ formed hydrogel.•The biomimetic nanoparticle was capable of inducing immunogenic cell death of ...tumor cells.•The alginate gel locally released XCL-1 to recruit regular DC cells into the tumor tissue.
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Immunogenic cell death (ICD) of tumor cells can produce plentiful tumor-associated antigens (TAAs) and release damage-associated molecules to communicate a danger situation. Damage-associated molecular patterns induce the antigen presentation ability of dendritic cells (DCs), activating the immune response cells and generating anti-tumor immune response. However, the immunosuppressive microenvironment in tumor tissues leads to a small amount of DCs in tumor tissues and suppresses their function, limiting the activation of immune response. Herein we report a tumor immunotherapy strategy by the combination of intravenous injection of doxorubicin (DOX)-loaded PLGA nanoparticles (DOX@P) coating with cell membranes (DOX@PM) and intratumoral injection of the lymphotactin (XCL-1)-loaded sodium alginate. The biomimetic nanocarriers facilitate the DOX targeted delivery to tumor, inducing a high degree of ICD. XCL-1 chemokines released from the in situ formed alginate hydrogel recruit a large amount of XCR-1+ DCs into the tumor tissue, which can capture more TAAs and mediate more cross-presentation of antigens to activate CD4+ and CD8+ T cells. As a result, in vivo antitumor experiments indicate that the double enhancement of immunogenic cell death and antigen presentation with this immunotherapy strategy improve the tumor therapy efficacy. This work provides a new strategy for enhanced tumor immunotherapy.
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•A novel ECL aptasensor based on Ag3PO4-NH2-SnO2 was developed.•NH2-SnO2 displayed a large surface to load numerous Ag3PO4.•The introducing of NH2-SnO2 greatly facilitated the ECL ...performance of Ag3PO4.•The as-prepared aptasensor provided a sensitive and specific method for acetamiprid assay.
Acetamiprid is a kind of broad-spectrum pesticides that has been largely applied in agriculture and household pest control. In this paper, a simple, novel and highly sensitive electrochemiluminescence aptamer sensor (ECL aptasensor) based on Ag3PO4-NH2-SnO2 was proposed. The ECL signal was greatly amplified with the synergistic effect of Ag3PO4 and NH2-SnO2 (Ag3PO4-NH2-SnO2) which was dropped on a glass carbon electrode (GCE) and used as working electrode. We designed an “on–off” ECL sensing strategy for the sensitive and specific detection of acetamiprid. Under the optimal conditions, the linear range of the sensor for acetamiprid detection was 1.0 × 10−11 ∼ 1.0 × 10−5 M, with a detection limit of 2.5 × 10−12 M (S/N = 3). The method showed simple and fast operation, high sensitivity and selectivity, strong anti-interference ability and good stability. More importantly, the developed aptasensor exhibited excellent recognition ability towards residual acetamiprid in actual water samples, which might open promising avenues to develop new ECL systems for biological analysis and environmental water monitoring.
Background
Overproduction and activation of osteoclasts result in various bone diseases, such as osteoporosis, Paget's disease, and rheumatoid arthritis. Thus, inhibiting osteoclast formation and ...overactivation may effectively prevent osteoclast‐related bone diseases, especially osteoporosis. Madecassic acid, one of the most important active ingredients in Centella asiatica, has various biological effects, but its role in osteoclastogenesis remains unknown.
Methods
RAW 264.7 cells were stimulated with receptor activator of nuclear factor (NF)‐κΒ ligand (RANKL, 25 ng/mL) to differentiate into multi‐nucleated osteoclasts. Subsequently, osteoclasts were treated with or without varying concentrations of madecassic acid (1, 2.5, 5, and 10 μmol/L).
Results
Madecassic acid significantly inhibited RANKL‐induced osteoclastogenesis in a concentration‐dependent manner. In addition, it reduced the percentage of bone resorptive area compared with the control, confirming that madecassic acid can inhibit osteoclast function. Furthermore, luciferase reporter gene studies indicate that madecassic acid could decrease the transcriptional activity of NF of activated T cells (NFAT) and NF‐κB in a dose‐dependent manner. Quantitative real‐time polymerase chain reaction results show that madecassic acid attenuated the expression of osteoclast‐associated genes, including V‐ATPase‐d2, cathepsin K, tartrate‐resistant acid phosphatase (TRAP), NFAT cytoplasmic 1 (NFATc1). Western blot analysis shows that madecassic acid inhibited RANKL‐mediated degradation of IκBα and NFATc1 expression, as well as phosphorylation of c‐Jun N‐terminal kinase (JNK) in RAW 264.7 cells.
Conclusion
Madecassic acid inhibited osteoclast formation and function in vitro by suppressing NF‐κB, JNK, and NFAT signaling pathways, indicating its potential as a novel drug for the treatment of osteoclast‐related bone diseases, especially osteoporosis.
Diagrammatic sketch for the action of madecassic acid treatment on the RANKL/RANK signaling pathway during osteoclast differentiation and bone resorption. Madecassic acid modulates osteoclast differentiation and bone resorption through the RANKL‐induced NF‐κB, JNK, and NFAT pathways. The red arrows indicate either downregulation or inhibition of osteoclasts. IκBα, inhibitor of κBα; JNK, c‐Jun N‐terminal kinase; NFATc1, nuclear factor of activated T cells 1; NF‐κB, nuclear factor‐κB; p‐JNK, phosphorylated JNK; RANK, receptor activator of nuclear factor‐κB; RANKL, RANK ligand; TRAP, tartrate‐resistant acid phosphatase.
Key points
Madecassic acid effectively inhibits RANKL‐induced osteoclast formation and function without affecting the viability of RAW 264.7 cells.
Madecassic acid can modulate osteoclastogenesis through RANKL‐induced signaling, including NF‐κB, JNK, and NFAT pathways.
Madecassic acid holds promise as a relatively safe therapeutic option for osteoclast‐related diseases.
Face completion is a domain-specific image inpainting problem. Most existing face completion methods fail to synthesize fine-grained facial structures due to the undifferentiated treatment of face ...images and other scene images. To handle this problem, we propose an end-to-end deep generative model based approach which makes full use of the facial prior knowledge, including 2D facial geometry priors from facial parsing maps and landmarks, as well as the 3D depth prior. We adopt a coarse-to-fine inpainting framework where the 2D facial geometry priors based on coarse faces are extracted to guide the refinement network for better planar facial textures and structures. Moreover, a novel 3D regularized reconstruction loss is proposed for the enhancement of the stereo perception of generated faces. Experimental results on two large-scale benchmarks CelebA and CelebA-HQ show that our method significantly outperforms the state-of-the-arts in generating more visually realistic and pleasing faces. Code is available at .
•A face completion network with both 2D and 3D facial priors is designed.•The 2D geometry priors composed of facial parsing maps and landmarks are proposed.•A novel 3D regularized construction loss is designed for better stereo perception.
This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.
First, RNA-sequencing (RNA-seq) data ...were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.
A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).
The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
The frequent occurrence of oil spills and oily wastewater leakage has increased the demand for oil-water separation materials with good hydrophobicity. Herein, a novel polylactic acid composite ...fibrous membrane is reported to address this problem. The zinc oxide decorated multi-wall carbon nanotubes were synthesized via the hydrothermal reaction and composited with polylactic acid to prepare a series of fibrous membranes via electrospinning. The wetting behavior of the prepared fibrous membranes conformed to Cassie's equation, proving that the introduced zinc oxide-decorated multi-wall carbon nanotubes enhanced the surface roughness of the prepared fibrous membranes. Such rough surfaces of the fibrous membranes have enhanced the hydrophobicity and increased the water contact angle to 138.5° (in air) and 159.3° (under oil), respectively. The oil uptake of the prepared fibrous membranes has reached 73.2 g/g. The prepared fibrous membrane was able to absorb oil on the water surface, underwater, or emulsion. Therefore, the prepared polylactic acid/zinc oxide-decorated multi-wall carbon nanotubes fibrous membrane can be a good candidate material for treating oily wastewater.
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The C-C bond constructed by Suzuki cross-coupling reaction is very important in the fields of medicine, chemical industry, etc. Here we support palladium on the surface of MOF@ partially carbonized ...PAN written as PAN(C) by solvothermal method to reduce the agglomeration of palladium and increase the catalytic performance of palladium. The physicalchemical properties of as-prepared catalysts were characterized using field emission scanning electron microscopy, transmission electron microscope (TEM), X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), Raman spectra, Fourier-transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and Temperature programmed reduction (H.sub.2-TPR). The catalyst is used in the Suzuki reaction, the yield is close to 100% and no significant reductions in performance after six reactions. It was found that there were synergistic effect and heterostructures between Ni-MOF and supported Pd, especially, the Pd and the carrier have a strong acting force, which ensures that the catalyst is used multiple times. Graphic A catalyst for hybridizing palladium on a composite support combining MOF and carbon fiber, Pd.sub.1-Ni.sub.4-MOF@CNF.sub.s are prepared via electrospinning technology followed by carbonization and a solvothermal process. They can be directly served as catalyst for Suzuki reaction. Most importantly, due to the synergistic effect and the influence of the heterostructure, the reaction yield was close to 100%, and the performance did not decrease significantly after six reactions.
Light emitting diode (LED) lamp has attracted increasing interest in the field of lighting systems due to its low energy and long lifetime. For different functions (i.e., illumination and color), it ...may have two or more performance characteristics. When the multiple performance characteristics are dependent, it creates a challenging problem to accurately analyze the system reliability. In this paper, we assume that the system has two performance characteristics, and each performance characteristic is governed by a random effects Gamma process where the random effects can capture the unit to unit differences. The dependency of performance characteristics is described by a Frank copula function. Via the copula function, the reliability assessment model is proposed. Considering the model is so complicated and analytically intractable, the Markov chain Monte Carlo (MCMC) method is used to estimate the unknown parameters. A numerical example about actual LED lamps data is given to demonstrate the usefulness and validity of the proposed model and method.
Objective To investigate the relationship between food patterns and mild cognitive impairment (MCI) among Chinese elderly to provide evidence for risk prevention and control of MCI among elderly ...population. Methods Between February 2017 to October 2018, a stratified multistage cluster sampling method was used to select participants from 760 communities of six districts in Xi'an, China, for 49-item food frequency questionnaire survey. A total of 2311 participants aged 60 to 88 years were included in the study with 444 (19.2%) participants of MCI among Chinese community-dwelling elderly adults. Food patterns associated with risk of dementia were assessed by using a reduced rank regression (RRR) analysis, and the multivariate linear regression was used to test trends of risk factors across scores for the food pattern. Results Four dietary patterns were extracted which explained 88.65% of the total variation in food intakes. Furthermore, the food pattern 1 (FP1) accounted for 60.25% of the total variation of all responsible variables and as a target dietary pattern in the study, which was related with high intake of legumes, vegetables, fruits, milk and dairy products, nuts and a low intake of noodles and cereals (p0.05). Multivariate linear regression analysis showed that participants with a high score for FP1 had higher direction, memory and language function and FP1 can improve the ability of cognitive function (p0.05). Conclusion The FP1 of Chinese dietary patterns was significantly correlated with higher cognitive function which can reduce the risk of MCI among Chinese elderly.
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