A Systematic Approach for Making 3D-Printed Patient-Specific Implants for Craniomaxillofacial Reconstruction

Craniomaxillofacial reconstruction implants, which are extensively used in head and neck surgery, are conventionally made in standardized forms. During surgery, the implant must be bended manually to match the anatomy of the individual bones. The bending process is time-consuming, especially for inexperienced surgeons. Moreover, repetitive bending may induce undesirable internal stress concentration, resulting in fatigue under masticatory loading in vivo and causing various complications such as implant fracture, screw loosening, and bone resorption. There have been reports on the use of patient-specific 3D-printed implants for craniomaxillofacial reconstruction, although few reports have considered implant quality. In this paper, we present a systematic approach for making 3D-printed patient-specific surgical implants for craniomaxillofacial reconstruction. The approach consists of three parts: First, an easy-to-use design module is developed using Solidworks® software, which helps surgeons to design the implants and the axillary fixtures for surgery. Design engineers can then carry out the detailed design and use finite-element modeling (FEM) to optimize the design. Second, the fabrication process is carried out in three steps: ① testing the quality of the powder; ② setting up the appropriate process parameters and running the 3D printing process; and ③ conducting post-processing treatments (i.e., heat and surface treatments) to ensure the quality and performance of the implant. Third, the operation begins after the final checking of the implant and sterilization. After the surgery, postoperative rehabilitation follow-up can be carried out using our patient tracking software. Following this systematic approach, we have successfully conducted a total of 41 surgical cases. 3D-printed patient-specific implants have a number of advantages; in particular, their use reduces surgery time and shortens patient recovery time. Moreover, the presented approach helps to ensure implant quality

2,4-Dinitrotoluene (DNT) Perturbs Yolk Absorption, Liver Development and Lipid Metabolism/Oxygen Transport Gene Expression in Zebrafish Embryos and Larvae

2,4-dinitrotoluene (2,4-DNT) is a common environmental pollutant, and was classified as a group 2B human carcinogenic compound by the International Agency for Research on Cancer. This study determined the toxic effects of 2,4-DNT exposure on zebrafish at the embryo-larvae stage, in terms of organ morphogenesis and the expression pattern of selected target genes related to lipid metabolism and oxygen transportation. The results showed that the 120-h post-fertilization LC50 of 2,4-DNT was 9.59 mg/L with a 95% confidence interval of 8.89–10.44 mg/L. The larvae treated with 2,4-DNT showed toxic symptoms including smaller body, less skin pigment production, yolk malabsorption, and disordered liver development. Further studies on the expression of genes related to lipid transport and metabolism, and respiration indicated that they were significantly affected by 2,4-DNT. It is concluded that 2,4-DNT exposure perturbed liver development and yolk absorption in early-life zebrafish, and disturbed the lipid metabolism /oxygen transport gene expression

Occurrence of Aflatoxin M1 in Three Types of Milk from Xinjiang, China, and the Risk of Exposure for Milk Consumers in Different Age-Sex Groups

Aflatoxin M1 (AFM1), a group 1 carcinogen, is a risk factor to be monitored in milk. This study aimed to investigate the occurrence of AFM1 in milk in Xinjiang, China, and to assess the risk of exposure for milk consumers in different age-sex groups. A total of 259 milk samples including pasteurized milk (93 samples), extended-shelf-life (ESL) milk (96), and raw donkey milk (70) were collected in Xinjiang from January to March in 2022. The AFM1 content of the milk samples was detected using a validated ELISA method. Of the 259 total samples analyzed for AFM1, 84 (32.4%) samples were contaminated at levels greater than the detection limit of 5 ng/L, with the maximum level of 16.5 ng/L. The positive rates of AFM1 in pasteurized milk and ESL milk were 43.0% (n = 40) and 45.8% (n = 44), respectively, and AFM1 was undetectable in donkey milk. The estimated daily intakes of AFM1 in each age group were lower than the hazard limits and were similar between male and female milk consumers. Therefore, the AFM1 contamination of milk in Xinjiang is low but still needs to be continuously monitored considering that children are susceptible to AFM1

Medium-Chain Triglycerides Attenuate Liver Injury in Lipopolysaccharide-Challenged Pigs by Inhibiting Necroptotic and Inflammatory Signaling Pathways

This study was conducted to investigate whether medium-chain triglycerides (MCTs) attenuated lipopolysaccharide (LPS)-induced liver injury by down-regulating necroptotic and inflammatory signaling pathways. A total of 24 pigs were randomly allotted to four treatments in a 2 × 2 factorial design including diet (0 and 4% MCTs) and immunological challenge (saline and LPS). After three weeks of feeding with or without 4% MCTs, pigs were challenged with saline or LPS. MCTs led to a significant increase in eicosapentaenoic acid, docosahexaenoic acid and total (n-3) polyunsaturated fatty acid concentrations. MCTs attenuated LPS-induced liver injury as indicated by an improvement in liver histomorphology and ultrastructural morphology of hepatocytes, a reduction in serum alanine aminotransferase and alkaline phosphatase activities as well as an increase in claudin-1 protein expression. In addition, MCTs also reduced serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 concentrations, liver TNF-α and IL-1β mRNA expression and protein concentrations and enhanced liver heat shock protein 70 protein expression in LPS-challenged pigs. Moreover, MCTs decreased mRNA expression of receptor-interacting serine/threonine-protein kinase (RIP) 3, mixed-lineage kinase domain-like protein (MLKL) and phosphoglycerate mutase 5 and inhibited MLKL phosphorylation in the liver. Finally, MCTs decreased liver mRNA expression of toll-like receptor (TLR) 4, nucleotide-binding oligomerization domain protein (NOD) 1 and multiple downstream signaling molecules. MCTs also suppressed LPS-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and increased extracellular signal-related kinase 1/2 phosphorylation in the liver. These results indicated that MCTs are capable of attenuating LPS-induced liver damage by suppressing hepatic necroptotic (RIP1/RIP3/MLKL) and inflammatory (TLR4/NOD1/p38 MAPK) signaling pathways

Effect of Baicalin-Aluminum Complexes on Fecal Microbiome in Piglets

The gut microbiome has important effects on gastrointestinal diseases. Diarrhea attenuation functions of baicalin (BA) is not clear. Baicalin–aluminum complexes (BBA) were synthesized from BA, but the BBA’s efficacy on the diarrhea of piglets and the gut microbiomes have not been explored and the mechanism remains unclear. This study has explored whether BBA could modulate the composition of the gut microbiomes of piglets during diarrhea. The results showed that the diarrhea rate reduced significantly after treatment with BBA. BBA altered the overall structure of the gut microbiomes. In addition, the Gene Ontology (GO) enrichment analysis indicated that the functional differentially expressed genes, which were involved in the top 30 GO enrichments, were associated with hydrogenase (acceptor) activity, nicotinamide-nucleotide adenylyltransferase activity, and isocitrate lyase activity, belong to the molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that flagellar assembly, bacterial chemotaxis, lipopolysaccharide biosynthesis, ATP-binding cassette transporters (ABC) transporters, biosynthesis of amino acids, and phosphotransferase system (PTS) were the most enriched during BBA treatment process. Taken together, our results first demonstrated that BBA treatment could modulate the gut microbiomes composition of piglets with diarrhea, which may provide new potential insights on the mechanisms of gut microbiomes associated underlying the antimicrobial efficacy of BBA

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Renal cell carcinoma (RCC) is the most common malignant tumor of the urinary system, and it has a high frequency of local invasion and distant metastasis. Although multiple advances have been made in the diagnosis and therapy of RCC, the vast majority of patients with metastatic RCC remain incurable. In this study, an aptamer named SW-4 against RCC 786-O cells was identified from a known sequence pool. The identified aptamer exhibited high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis revealed that SW-4 only bound to RCC 786-O cells, but not HEK293T cells or human proximal tubular HK-2 cells, indicating that SW-4 has excellent binding selectivity. By sequence optimization, the 26-nt truncated SW-4b demonstrated improved binding affinity, and it was internalized into target cells via caveolae-mediated endocytosis in a temperature-dependent manner. Furthermore, fluorescence imaging confirmed that SW-4b accumulated at tumor sites in 786-O xenograft nude mice models and specifically recognized clinical RCC tissues. Meanwhile, SW-4b inhibited proliferation of 786-O cells by arresting cell cycle progression at the S phase. Taken together, these results indicate that SW-4b is a potential candidate for development into a novel tool for diagnosis and targeted therapy of RCC. Keywords: renal cell carcinoma, aptamer, binding affinity, internalization, proliferatio