Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while the 5‐y survival of osteosarcoma patients gained no significant improvement over the past decades. This ...study aimed to explore the role of ferroptosis‐related genes (FRGs) in the development and prognosis of osteosarcoma. The datasets of osteosarcoma patients including RNA sequencing data and clinical information were acquired from the TRGET and Gene Expression Omnibus (GEO) databases. The identification of molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. The prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The ESTIMATE algorithm was applied for determining the stromal score, immune score, ESTIMA score, and tumor purity of osteosarcoma patients. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the underlying mechanisms in the development and prognosis of osteosarcoma. Two molecular subgroups with different FRGs expression patterns were identified. The molecular subgroups with higher immune score and more active immune status showed better prognostic survival. On the basis of FRGs, a prognostic model and a nomogram integrating clinical characteristics were constructed and their prediction efficiency for osteosarcoma prognosis were well validated. Gene functional enrichment analysis showed that these differentially expressed FRGs were mainly enriched in immunity‐related signaling pathways, indicating that FRGs may affect the development and prognosis of osteosarcoma by regulating the immune microenvironment. The expression profiles of FRGs were closely related to the immunity status and prognostic survival of osteosarcoma patients. The interaction between ferroptosis and immunity in the development of osteosarcoma could provide a new insight into the exploration of molecular mechanisms and targeted therapies of osteosarcoma patients.
Ferroptosis‐related gene signature associates with immunity and predicts prognosis of osteosarcoma.
Lower respiratory tract (LRT) microbiome has been reported to associate with pulmonary diseases. Unregulated inflammation is an underlying cause of variable lung diseases. The lung microbiome may ...play an important role in the smoking-induced inflammatory lung diseases. What's more, the function of microbiome may be more important for understanding how microbes interact with host. Our study aims to explore the effects of smoking on the lower respiratory tract microbiome, the association between variation of lower respiratory tract microbiome and inflammation and whether smoking exposure changes the function of lower respiratory tract microbime.
Forty male mice were randomly divided into smoking group and non-smoking group, and the smoking group was exposed to cigarette smoke for 2 h per day for 90 days. After experiment, the blood samples were collected to measure the concentration of interleukin-6 (IL-6) and C reactive protein (CRP) by ELISA. Lung tissue samples were used to detect the community and diversity of lower respiratory tract microbiome through 16S rRNA gene quantification and sequencing technology. ANOSIM and STAMP were performed to analyze the differences of the microbial community structure between smoking group and non-smoking group. SPSS 24.0 software was used to analyze the correlations between microbiome and inflammation mediators through scatter plots and Spearman correlation coefficient. Microbial metabolic function was predicted by PICRUSt based on the 16 s rRNA gene quantification and sequencing results. PATRIC database was searched for the potential pathogenic bacteria in lower respiratory tract.
Our results suggested that smoking had markedly effects on the microbiota structure of lower respiratory tract based on Bray-Curtis distance (R
= 0.084, p = 0.005) and on unweighted uniFrac distance (R
= 0.131, p = 0.002). Smoking mainly affected the abundance of microbiome which belong to Proteobacteria phyla and Firmicutes phyla. Moreover, our results also found that smoking increased the abundance of Acinetobacter, Bacillus and Staphylococcus, which were defined as pathogenic bacteria. Inflammatory mediators were observed to associate with certain microbiome at every level. Most of microbiome which were associated with inflammation belonged to Proteobacteria phyla or Firmicutes phyla. Moreover, we found that the decreased microbiome in smoking group, including Oceanospirillales, Desulfuromonadales, Nesterenkonia, and Lactobacillaceae, all were negatively correlated with IL-6 or CRP. Based on the level of inflammation, the abundance of microbiome differs. At genus level, Lactobacillus, Pelagibacterium, Geobacter and Zoogloea were significantly higher in smoking group with lower IL-6 concentration. The abundance of microbiome was not observed any statistical difference in subgroups with different weight. Three dominant genus, defined as pathogen, were found higher in the smoking group. The microbial functional prediction analysis revealed that ABC-type transport systems, transcription factors, amino acide transport and metabolism, arginine and proline metabolism et al. were distinctively decreased in smoking group, while the proportions of replication, recombination and repair, ribosome, DNA repair and recombination proteins were increased in smoking group (q < 0.05).
Members of Proteobacteria phyla and Firmicutes phyla played an important role in the microbial community composition and keeping a relatively balanced homeostasis. Microbiome dysbiosis might break the balance of immune system to drive lung inflammation. There might exist potential probiotics in lower respiratory tract, such as Lactobacillaceae. The altered function of Lower respiratory tract microbiome under smoking exposure may affect the physiological homeostasis of host.
Carbon nanotube (CNT) thin-film transistor (TFT) is a promising candidate for flexible and wearable electronics. However, it usually suffers from low semiconducting tube purity, low device yield, and ...the mismatch between p- and n-type TFTs. Here, we report low-voltage and high-performance digital and analog CNT TFT circuits based on high-yield (19.9%) and ultrahigh purity (99.997%) polymer-sorted semiconducting CNTs. Using high-uniformity deposition and pseudo-CMOS design, we demonstrated CNT TFTs with good uniformity and high performance at low operation voltage of 3 V. We tested forty-four 2-µm channel 5-stage ring oscillators on the same flexible substrate (1,056 TFTs). All worked as expected with gate delays of 42.7 ± 13.1 ns. With these high-performance TFTs, we demonstrated 8-stage shift registers running at 50 kHz and the first tunable-gain amplifier with 1,000 gain at 20 kHz. These results show great potentials of using solution-processed CNT TFTs for large-scale flexible electronics.
A four-dimensional (4D) ensemblevariational data assimilation (DA) system (4DEnsVar) was developed, building upon the infrastructure of the gridpoint statistical interpolation (GSI)-based hybrid DA ...system. 4DEnsVar used ensemble perturbations valid at multiple time periods throughout the DA window to estimate 4D error covariances during the variational minimization, avoiding the tangent linear and adjoint of the forecast model. The formulation of its implementation in GSI was described. The performance of the system was investigated by evaluating the global forecasts and hurricane track forecasts produced by the NCEP Global Forecast System (GFS) during the 5-week summer period assimilating operational conventional and satellite data. The newly developed system was used to address a few questions regarding 4DEnsVar. 4DEnsVar in general improved upon its 3D counterpart, 3DEnsVar. At short lead times, the improvement over the Northern Hemisphere extratropics was similar to that over the Southern Hemisphere extratropics. At longer lead times, 4DEnsVar showed more improvement in the Southern Hemisphere than in the Northern Hemisphere. The 4DEnsVar showed less impact over the tropics. The track forecasts of 16 tropical cyclones initialized by 4DEnsVar were more accurate than 3DEnsVar after 1-day forecast lead times. The analysis generated by 4DEnsVar was more balanced than 3DEnsVar. Case studies showed that increments from 4DEnsVar using more frequent ensemble perturbations approximated the increments from direct, nonlinear model propagation better than using less frequent ensemble perturbations. Consistently, the performance of 4DEnsVar including both the forecast accuracy and the balances of analyses was in general degraded when less frequent ensemble perturbations were used. The tangent linear normal mode constraint had positive impact for global forecast but negative impact for TC track forecasts.
Summary
Microporous film and MAP were evaluated to find the optimal method for extending the postharvest storage of strawberry. To determine the most suitable MAP system for strawberry, fruits were ...stored in controlled atmospheres (O2/CO2 partial pressures in kPa: 5/10; 10/10; 5/15), and in a separate experiment, strawberries were sealed in the container with different microporous PET/PE films. Results showed that the optimum atmosphere of strawberries was 10 kPa O2 + 10 kPa CO2 which could be achieved and maintained by using the microporous film with four perforations of 100 μm. By maintaining the optimal atmosphere, active EMAP could increase polyphenol compounds accumulation, with total phenolic content increased by 25% and the content of anthocyanin and total flavonoid was 13% and 29% higher than control at the end of storage. Meanwhile, active EMAP significantly increased CAT PAL and APX activities and the shelf‐life was prolonged for 6 and 3 days, respectively, compared with strawberries packed in control and passive EMAP.
Novel equilibrium modified atmosphere packaging (EMAP) system for strawberry has been studied. EMAP configurations were designed by means of a validated mathematical model and confirmed by experiment. EMAP improved gas and water vapour transmission by microperforation on laminated lidding films. EMAP treatment effectively maintained higher quality and preserved antioxidant substances in strawberries.
Organic electrochemical transistors (OECTs) utilize ion flow from the electrolyte to modulate the electrical conductivity of the whole bulk organic semiconductor channel. With the characteristic of ...mixed ionic‐electronic conducting in the entire volume, OECTs exhibit high transconductance and act as good transducers, particularly in bioelectronics. To gain high‐performance OECTs, developing novel high‐performance polymeric semiconductors is important. In this article, operation principles, performance evaluations, and polymerization methods are first discussed. We then analyze the molecular design strategies for high‐performance OECT materials and highlight the characteristics and effects of backbone design and side chain engineering. Finally, we discuss some neglected and unsolved issues and provide an outlook for the OECTs research and development.
Abstract
High-performance n-type organic electrochemical transistors (OECTs) are essential for logic circuits and sensors. However, the performances of n-type OECTs lag far behind that of p-type ...ones. Conventional wisdom posits that the LUMO energy level dictates the n-type performance. Herein, we show that engineering the doped state is more critical for n-type OECT polymers. By balancing more charges to the donor moiety, we could effectively switch a p-type polymer to high-performance n-type material. Based on this concept, the polymer, P(gTDPP2FT), exhibits a record high n-type OECT performance with
μC
* of 54.8 F cm
−1
V
−1
s
−1
, mobility of 0.35 cm
2
V
−1
s
−1
, and response speed of
τ
on
/
τ
off
= 1.75/0.15 ms. Calculations and comparison studies show that the conversion is primarily due to the more uniform charges, stabilized negative polaron, enhanced conformation, and backbone planarity at negatively charged states. Our work highlights the critical role of understanding and engineering polymers’ doped states.
Four polymers that contain alkyl chains branched at different positions on the polymer backbone are prepared. A polymer with 4‐decyltetradecyl chains gives an impressive mobility of 3.62 cm2 V−1 s−1. ...This may arise from tighter polymer packing as well as stacking conformation change of the polymer backbone induced by the branching of the alkyl chains.
Intelligent nanomaterials open up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of simple enzymatically cleavable self‐delivery nanoparticles ...(MA‐pepA‐Ce6 NPs) is developed by conjugating acidic‐sensitive small‐molecule programmed cell death ligand 1 (PD‐L1) inhibitor (Metformin, MET) with photosensitizer (chlorin e6, Ce6) through matrix metalloproteinase‐2 (MMP‐2) cleavable peptide (GPLGVRGDK, pepA). Noticeably, these self‐delivery peptide‐based NPs can circumvent the controversial biosafety facing nanomaterials. Moreover, MA‐pepA‐Ce6 NPs are degraded by overexpressed MMP‐2 in tumor microenvironment (TME) and expose the VRGDK‐Ce6. The exposed VRGDK‐Ce6 shows superior targeting ability towards integrin αvβ3 receptor, ensuring sufficient accumulation and laser‐activated robust antitumor immune effects. Remarkably, the released MET in tumor microenvironment hampers the PD‐L1 expression and augments the antitumor immune response elicited by photodynamics therapy (PDT), thus significantly improving therapeutic outcomes. Overall, this study offers a potential appealing paradigm of synergistic PDT‐triggered immunotherapy by revealing MET‐mediated PD‐L1 downregulation to achieve tumor eradication.
A new self‐delivery nanoparticle (MA‐pepA‐Ce6 NP) for co‐delivering a photosensitizer (chlorin e6) and small‐molecule programmed cell death ligand 1 (PD‐L1) inhibitor (Metformin) is constructed. Simple and biodegradable materials endow safety. Tumor microenvironment‐specific stimuli responses enable effective drug accumulation. More importantly, the combination of photodynamic therapy and PD‐L1 inhibition induces effective antitumor immune responses, indicating the potential application in cancer immunotherapy.
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