Investigations into the effects of scaffold microstructure on slow-release system with bioactive factors for bone repair

In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 μm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%–80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively

Lost in Luxury: Climate Change and Silk Consumption in Mid-Qing China (1735–1840 CE)

A quantitative approach has been promoted to understand the history of climate and society. Statistical research on luxurious expenses under climate change in past societies remains insufficient, however. Hence, this study statistically examined the association between climate change and the imperial court’s luxury expenses on silk products in mid-Qing China (1735–1840 CE) by including major ecological–social–economic stresses. Results indicated that the Qing imperial court’s silk consumption increased under favorable climatic conditions and a flourishing agrarian economy, and vice versa. Natural disasters and social crises hardly affected the Qing imperial court’s silk consumption, however, suggesting its limited support and inactive attitude toward ecological–social–economic stresses. Such an institutional weakness might have increased social vulnerability, which could have led to Qing China’s decline since the eighteenth century. The study serves as the first attempt to reveal a long-term historical climate–luxury linkage and further provides a supplementary explanation of the economic decline from the perspective of the history of climate and society. Based on past lessons, this study emphasizes institutional activeness to tackle upcoming climate change challenges

Impact Resistant Structure Design and Optimization Inspired by Turtle Carapace

The turtle carapace has a high level of protection, due to its unique biological structure, and there is great potential to use the turtle carapace structure to improve the impact resistance of composite materials using bionic theory. In this paper, the chemical elements of the turtle carapace structure, as well as its mechanical properties, were investigated by studying the composition of the compounds in each part. In addition, the bionic sandwich structure, composed of the plate, core, and backplate, was designed using modeling software based on the microstructure of the keratin scutes, spongy bone, and the spine of the turtle carapace. Additionally, finite element analysis and drop-weight experiments were utilized to validate the impact-resistant performance of the bionic structures. The numerical results show that all of the bionic structures had improved impact resistance to varying degrees when compared with the control group. The experimental results show that the split plate, the core with changing pore gradients, and the backplate with stiffener all have a considerable effect on the impact-resistance performance of overall composite structures. This preliminary study provides theoretical support for composite material optimization

Impact Resistant Structure Design and Optimization Inspired by Turtle Carapace

The turtle carapace has a high level of protection, due to its unique biological structure, and there is great potential to use the turtle carapace structure to improve the impact resistance of composite materials using bionic theory. In this paper, the chemical elements of the turtle carapace structure, as well as its mechanical properties, were investigated by studying the composition of the compounds in each part. In addition, the bionic sandwich structure, composed of the plate, core, and backplate, was designed using modeling software based on the microstructure of the keratin scutes, spongy bone, and the spine of the turtle carapace. Additionally, finite element analysis and drop-weight experiments were utilized to validate the impact-resistant performance of the bionic structures. The numerical results show that all of the bionic structures had improved impact resistance to varying degrees when compared with the control group. The experimental results show that the split plate, the core with changing pore gradients, and the backplate with stiffener all have a considerable effect on the impact-resistance performance of overall composite structures. This preliminary study provides theoretical support for composite material optimization

RSAD2 Is an Effective Target for High-Yield Vaccine Production in MDCK Cells

Increasingly, attention has focused on improving vaccine production in cells using gene editing technology to specifically modify key virus regulation-related genes to promote virus replication. In this study, we used DIA proteomics analysis technology to compare protein expression differences between two groups of MDCK cells: uninfected and influenza A virus (IAV) H1N1-infected cells 16 h post infection (MOI = 0.01). Initially, 266 differentially expressed proteins were detected after infection, 157 of which were upregulated and 109 were downregulated. We screened these proteins to 23 genes related to antiviral innate immunity regulation based on functional annotation database analysis and verified the mRNA expression of these genes using qPCR. Combining our results with published literature, we focused on the proteins RSAD2, KCNN4, IDO1, and ISG20; we verified their expression using western blot, which was consistent with our proteomics results. Finally, we knocked down RSAD2 using lentiviral shRNA expression vectors and found that RSAD2 inhibition significantly increased IAV NP gene expression, effectively promoting influenza virus replication with no significant effect on cell proliferation. These results indicate that RSAD2 is potentially an effective target for establishing high-yield vaccine MDCK cell lines and will help to fully understand the interaction mechanism between host cells and influenza viruses

Suppression of the METTL3-m6A-integrin β1 axis by extracellular acidification impairs T cell infiltration and antitumor activity

Summary: The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the “tumor acidity (TuAci) score” for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin β1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy

TGM2 inhibits the proliferation, migration and tumorigenesis of MDCK cells.

Madin-Darby canine kidney (MDCK) cells are one of the main cell lines used for influenza vaccine production due to their high virus yield and low mutation resistance. Due to their high tumorigenicity, the safety of vaccines produced from these cells is controversial. TGM2 is a multifunctional protein that plays an important role in the adhesion and migration of cells and is associated with tumor formation. We found that the expression level of TGM2 was significantly up-regulated in low tumorigenic MDCK cells. We first analyzed TGM2-overexpressed and knockout MDCK cells in vitro. Scratch-wound assay and Transwell chamber experiments showed that TGM2 overexpression significantly inhibited the migration and invasion of MDCK cells and significantly reduced their proliferation. TGM2 knockout significantly enhanced cell migration, invasion, and proliferation. The tumorigenesis results in nude mice were consistent with those in vitro. TGM2 knockout significantly enhanced the tumorigenesis rate of MDCK cells in nude mice. We also investigated the effects of TGM2 gene expression on the replication of the H1N1 influenza A virus in MDCK cells. The results showed that TGM2 induced the negative regulation of H1N1 replication. These findings contribute to a comprehensive understanding of the tumor regulation mechanism and biological functions of TGM2

Insights into Persistent Toxic Substances in Protective Cases of Mobile Phones: Occurrence, Health Risks, and Implications

Despite the popularity of smartphones worldwide, persistent toxic substances (PTSs) in protective cases of mobile phones (PCMPs) and their health risks via direct skin contact have been ignored. This study investigated PTSs in PCMPs made in China with different materials and sales territory and their potential harm to human health. Polybrominated diphenyl ethers (PBDEs, 6.40 ng/g), new brominated flame retardants (NBFRs, 144 ng/g), organophosphate esters (OPEs, 10.1 mu g/g), short-chain chlorinated paraffins (SCCPs, 3.58 mu g/g), medium-chain chlorinated paraffins (MCCPs, 3.17 mu g/g), and heavy metals (HMs, 72.3 mu g/g) were detected. It was found that the different concentrations and compositions depend on the material, region, and use. Moreover, the raw materials used to fabricate PCMPs are of variable quality and may include recycled plastic waste. There are no standard quality specifications for PCMPs, and different materials have different properties, including specific surface area and adsorption ability. The risk assessment performed by Monte Carlo simulations indicated that the PTSs evaluated pose no health risks to the general population and may have adverse effects on individual high-exposure populations. According to the results of this work, it is suggested that more stringent global specifications for the selection of raw materials should be established, including the content and structural characteristics of PTSs, limitations on the use of additives in the production process, and the handling after use