Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules

Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive.Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES).Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations.Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens

Influences of the Tibetan plateau on tidal gravity detected by using SGs at Lhasa, Lijiang and Wuhan Stations in China

We accurately retrieved tidal gravimetric parameters using long-term continuous tidal gravity measurements recorded by superconducting gravimeters (SGs) at stations in Lhasa, Lijiang, and Wuhan, China. We used these results to investigate the influences of the special tectonic setting on regional tidal deformation. We accurately evaluated scale factors of SGs with high precision better than 0.06%. We carefully removed the effects of barometric pressure and oceanic loading from tidal gravity observations. We did not observe any obvious differences in amplitude factors for main tidal gravity waves for the stations in Lhasa and Lijiang. In the plateau area, we found the amplitude factor to be about 0.34% larger than that in the plain (Wuhan). Our study shows for the first time that the main reason for such tidal gravity anomalies can be explained by the influence of the special tectonic setting in the Tibetan Plateau

Folic Acid-Decorated <i>β</i>-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy

Effects of Fumonisin B and Hydrolyzed Fumonisin B on Growth and Intestinal Microbiota in Broilers

Fumonisins are mainly produced by Fusarium verticillioides and proliferatum, which causes a variety of toxicities in humans and animals, including fumonisin Bs (FBs) as the main form. After they are metabolized by plants or microorganisms, modified fumonisins are difficult to detect by conventional methods, which result in an underestimation of their contamination level. Fumonisins widely contaminate maize and maize products, especially in broiler feed. As an economically important food, broilers are often adversely affected by mycotoxins, leading to food safety hazards and high economic losses. However, there are few studies regarding the adverse effects of FBs on broiler growth and health, especially modified FBs. Our data shows that after exposure to FBs or hydrolyzed fumonisin Bs (HFBs), the body weight and tissue weight of broilers decreased significantly, especially the testes. Moreover, they significantly affect the intestinal microbiota and the relative abundance of bacteria from phylum-to-species levels, with the differentially affected bacteria mainly belonging to Firmicutes and Proteobacteria. Our findings suggest that both the parent and hydrolyzed FBs could induce growth retardation, tissue damage and the imbalance of intestinal microbiota in broilers. This indicated that the harmful effects of HFBs cannot be ignored during food safety risk assessment

Early-Age Mechanical Characteristics and Microstructure of Concrete Containing Mineral Admixtures under the Environment of Low Humidity and Large Temperature Variation

The application of concrete containing mineral admixtures was attempted in Northwest China in this study, where the environment has the characteristics of low humidity and large temperature variation. The harsh environment was simulated by using an environmental chamber in the laboratory and four types of concrete were prepared, including ordinary concrete and three kinds of mineral admixture concretes with different contents of fly ash and blast-furnace slag. These concretes were cured in the environmental chamber according to the real curing conditions during construction. The compression strength, fracture properties, SEM images, air-void characteristics, and X-ray diffraction features were researched at the early ages of curing before 28 d. The results showed that the addition of fly ash and slag can improve the compression strength and fracture properties of concrete in the environment of low humidity and large temperature variation. The optimal mixing of mineral admixture was 10% fly ash and 20% slag by replacing the cement in concrete, which can improve the compression strength, initial fracture toughness, unstable fracture toughness, and fracture energy by 23.9%, 25.2%, 45.3%, and 22.6%, respectively, compared to ordinary concrete. Through the analysis of the microstructure of concrete, the addition of fly ash and slag can weaken the negative effects of the harsh environment of low humidity and large temperature variation on concrete microstructure and cement hydration

Three-Dimensional-Printed Guiding Template for Unicompartmental Knee Arthroplasty

Background. For unicompartmental knee arthroplasty (UKA), accurate alignment of the limb is crucial. This study is aimed at investigating the efficacy and safety of a three-dimensional printed patient-customized guiding template (3DGT) for UKA. Methods. A total of 22 patients receiving UKA were randomly divided into the 3DGT-UKA group (n=11) and traditional UKA group (T-UKA group; n=11). In the 3DGT-UKA group, the line and angle of osteotomy were decided on a 3D image of the limb reconstructed from imaging data; a guiding template was then designed and printed out. The patients in the T-UKA group underwent conventional UKA. Prosthesis size, operation time, postoperative drainage, hip–knee angle (HKA), pain, and Hospital for Special Surgery (HSS) scores were recorded at day 1, week 1, month 1, and month 3 after surgery. Results. There was no significant difference in the size of prostheses between the preoperatively designed and actually used in the 3DGT-UKA group (p>0.05). HKA was comparable in 3DGT-UKA and T-UKA patients. Operation time was shorter (53.6±6.4 minutes vs. 75.8±7.1 minutes) and wound drainage was less (93.2±3.9 mL vs. 85.2±3.0 mL) in 3DGT-UKA than in T-UKA (p<0.05). Hospital stay was shorter in the 3DGT-UKA group. The 3DGT-UKA group had a lower VAS score on day 1, week 1, and month 1 and a higher HSS score on week 1 and month 1 after surgery. No varus/valgus deformity or prosthesis loosening was observed in either group at the final follow-up. Conclusion. The 3D-printed patient-customized guiding template may help decrease operation time, decrease blood loss, and improve short-term clinical outcomes in patients undergoing UKA surgery