Support Removal on Thin-Walled Parts Produced by Laser Powder Bed Fusion.

Support removal is one of the thorny issues faced by laser powder bed fusion (LPBF). In particular, the efficient and safe removal of support structures from the thin-walled parts and obtaining high-quality surfaces still remains a challenge owing to their sensitivity to machining. An in-depth understanding of the material response behavior of LPBF thin-walled parts when removing support structures is necessary for overcoming this challenge. The work is divided into two parts: revealing the support removal mechanism and proposing a solution to improve the support machinability. First, the machinability of support structures on thin-walled parts with different thicknesses at different cutting depths was thoroughly investigated. Experimental investigation on cutting force, surface morphology, and deflection were carried out. The results show that cutting forces increase gradually at each cut owing to the tilt and collapse of support structures. The surface morphology is improved as the sample thickness increases but deteriorated as the cutting depth increases. Second, a novel solution of adding resin is proposed to improve the support machinability and good results have been achieved. The z-direction cutting forces for 0.3 and 0.4 mm thickness samples are reduced by 72.6% and 64.6%, respectively, and no deflection of the sample is observed after support removal. Moreover, finite element method simulations are established to further explain the support removal mechanism.

The design and processing of a 3D-printed high-performance biological fixation plate.

In order to generate a high-performance personalized biological fixation plate with matching mechanical properties and biocompatibility, reverse reconstruction and fracture reduction of a femur were performed by combining reverse and forward approaches, and the surface was extracted according to the installation position of the plate to complete plate modeling by shifting, thickening, and performing other operations. Subsequently, topology optimization and three-dimensional (3D) printing were performed, and the properties of the manufactured plate were probed. The results showed that the maximum displacement of the plate was 4.13 mm near the femoral head, the maximum stress was 5.15e2 MPa on both sides of the plate across its entire length, and the stress concentration decreased following topology optimization. The plate with optimized topology and filled with porous structure has a good filling effect. The final mass of the H-shaped plate was 12.05 g, while that of the B-shaped plate was 11.05 g, which dropped by 20.93% and 27.49%, respectively, compared with the original plate. The surface of the 3D-printed plate was bright and new, with a clear pore structure and good lap joint. The B-shaped and H-shaped plates were closely dovetailed with the host bone, which met the assembly requirements. This lays a foundation for the direct application of a high-performance personalized biological fixation plate.

Integrating Metabolomics and Network Pharmacology to Explore the Mechanism of Tongmai Yangxin Pills in Ameliorating Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in clinical treatment of malignant tumors. It has a high anticancer activity but also high cardiotoxicity. The aim of this study was to explore the mechanism of Tongmai Yangxin pills (TMYXPs) in ameliorating DOX-induced cardiotoxicity through integrated metabolomics and network pharmacology. In this study, first, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) metabonomics strategy was established to obtain metabolite information and potential biomarkers were determined after data processing. Second, network pharmacological analysis was used to evaluate the active components, drug-disease targets, and key pathways of TMYXPs to alleviate DOX-induced cardiotoxicity. Targets from the network pharmacology analysis and metabolites from plasma metabolomics were jointly analyzed to select crucial metabolic pathways. Finally, the related proteins were verified by integrating the above results and the possible mechanism of TMYXPs to alleviate DOX-induced cardiotoxicity was studied. After metabolomics data processing, 17 different metabolites were screened, and it was found that TMYXPs played a role in myocardial protection mainly by affecting the tricarboxylic acid (TCA) cycle of myocardial cells. A total of 71 targets and 20 related pathways were screened out with network pharmacological analysis. Based on the combined analysis of 71 targets and different metabolites, TMYXPs probably played a role in myocardial protection through regulating upstream proteins of the insulin signaling pathway, MAPK signaling pathway, and p53 signaling pathway, as well as the regulation of metabolites related to energy metabolism. They then further affected the downstream Bax/Bcl-2-Cyt c-caspase-9 axis, inhibiting the myocardial cell apoptosis signaling pathway. The results of this study may contribute to the clinical application of TMYXPs in DOX-induced cardiotoxicity.

Mechanisms underlying the toxicity of microplastics to mammals: a review / 预防医学

@#As a new type of environmental pollutants, microplastics are widely distributed in the global ecosystem, and ingestion of microplastics may produce a number of toxic effects. Based on currently available publications, this paper describes the main pathways of exposure to microplastics, and summarizes the toxic mechanisms of microplastics in mammals, including oxidative stress, inflammatory response, immune damage, imbalance of gut microbiota, energy metabolism disorder and DNA damage, so as to provide insights into elucidation of the toxic mechanism mechanisms and health risk assessment of microplastics.

Occurrence and Health Risks of Heavy Metals in Drinking Water of Self-Supplied Wells in Northern China.

Self-supplied wells, an important water resource in remote and scattered regions, are commonly deteriorated by environmental pollution and human activity. In this study, 156 self-supplied well-water samples were collected from remote and scattered areas of Inner Mongolia (NMG), Heilongjiang (HLJ), and the suburbs of Beijing (BJ) in Northern China. Twenty-four heavy metals were identified by using the inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES), and the associated human health risks were assessed by using standards of the US Environmental Protection Agency (US EPA). The concentrations of four heavy metals (As, Fe, Mn, and Tl) in HLJ, one heavy metal (Tl) in BJ, and ten heavy metals (Al, As, B, Cr, Fe, Mn, Mo, Se, Tl, and Zn) in NMG exceeded the limits set by China or the World Health Organization (WHO). The total carcinogenic risk (TCR) and total non-carcinogenic risk (THQ) exceeding set limits mainly occurred in NMG, compared to HLJ and BJ. Moreover, As accounted for 97.87% and 60.06% of the TCR in HLJ and BJ, respectively, while Cr accounted for 70.83% of the TCR in NMG. The TCR caused by Cd in all three areas had a negligible hazard (<10-4). As accounted for 51.11%, 32.96%, and 40.88% of the THQ in HLJ, BJ, and NMG, respectively. According to the results of the principal component analysis, heavy metals in well water from HLJ and NMG mainly originated from mixed natural processes and anthropogenic sources, whereas, in BJ, most heavy metals probably originated from natural sources. In the future, long-term monitoring of heavy metals in water from self-supplied wells should be conducted for an extensive range of well-water sites, and well water with high As contamination should be monitored more and fully assessed before being used as a drinking-water source.

Comprehensive Analysis of Differentially Expressed lncRNAs miRNAs and mRNA and Their ceRNA Network of Patients With Rare-Earth Pneumoconiosis.

Rare-earth pneumoconiosis (REP) is the main occupational disease of rare earth exposed workers and there is no specific treatment. In this study, we performed high-throughput sequencing on the plasma of nine REP to describe and analyze the expression profiles of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA and investigate their regulatory networks. Our results identified a total of 125 lncRNAs, 5 miRNAs, and 82 mRNAs were differentially expressed in the plasma of patients with REP. Furthermore, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed non-coding RNAs (ncRNA). We found the differential expression of ncRNA are mainly related to the response of cells to stimulation, Hedgehog signaling pathway and so on. We also constructed lncRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in REP. We found that in the competitive endogenous RNA (ceRNA) networks, lncRNA acts as a sponge of miRNA to regulate the target gene. The expression results were verified by qRT-PCR and the protein interaction networks of differentially expressed genes were constructed via the STRING database. OncoLnc online platform was used to do the lung cancer survival analysis among the top five mRNA analyzed by Protein-protein interaction (PPI) network analysis. We found miR-16-2-3p may used as biomarker for REP, because it is closely related to the occurrence and prognosis of REP through inflammatory reaction and in lung squamous cell carcinoma, its expression levels were positively correlated with the overall survival rate of patients.

A review on cationic lipids with different linkers for gene delivery.

Cationic lipids have become known as one of the most versatile tools for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Most of cationic lipids share the common structure of cationic head groups and hydrophobic portions with linker bonds between both domains. The linker bond is an important determinant of the chemical stability and biodegradability of cationic lipid, and further governs its transfection efficiency and cytotoxicity. Based on the structures of linker bonds, they can be grouped into many types, such as ether, ester, amide, carbamate, disulfide, urea, acylhydrazone, phosphate, and other unusual types (carnitine, vinyl ether, ketal, glutamic acid, aspartic acid, malonic acid diamide and dihydroxybenzene). This review summarizes some research results concerning the nature (such as the structure and orientation of linker groups) and density (such as the spacing and the number of linker groups) of linker bond for improving the chemical stability, biodegradability, transfection efficiency and cytotoxicity of cationic lipid to overcome the critical barriers of in vitro and in vivo transfection.