Search

Abstract There is no consensus about whether relatively large mediastinal tumors (≥ 5.0 cm) are suitable for video-assisted thoracoscopic surgery (VATS). Therefore, this study aimed to compare the efficacy and safety of intercostal approach VATS for large-sized anterior mediastinal tumors (5.0–10.0 cm) with no invasion to the surrounding tissues and organs. A total of 129 patients with anterior mediastinal tumors who received surgery in our hospital between January 2018 and July 2022 were consecutively enrolled. Patients were divided into 2 groups based on mediastinal tumor diameter: Group A (tumor size between 1.0 and 4.9 cm) and Group B (tumor size between 5.0 and 10.0 cm). The primary endpoints were operation time, blood loss, and postoperative pain, and the secondary endpoints were the volume of drainage, drainage duration, postoperative hospital stay, and postoperative complications. Significant differences were found in the volume of drainage between the two groups (Group A: 218.4 ± 140.6, Group B: 398.9 ± 369.3, P 0.05). In addition, there existed no significant differences in the postoperative complications. Intercostal approach VATS is regarded as a feasible and safe surgical method for large-sized anterior mediastinal tumors (5.0–10.0 cm) with no invasion to the surrounding tissues and organs.

[Objective] The new technique of small-diameter TBM (tunnel boring machine) advancing excavations followed by large-diameter TBM enlargement is used for the first time in the construction of Tumor Hospital Station on Shenzhen Metro Line 14. As the geological stability is hard to be predicted when the large diameter TBM advances in the artificial composite geological stratum, which is back-filled after the small diameter TBM excavation, it is necessary to simulate and analyze the station built with such construction technique. [Method] MIDAS/GTS software is used to simulate the effect of different backfill materials and buried depths on ground settlement and on the stress of the segment structure when the excavation of the large shield tunnel and the construction of support structure are completed. [Result & Conclusion] The analysis results show that when C40 concrete, C15 concrete and muck are respectively used as backfill materials, the stratum displacement and the maximum stress of the segment structure caused by the large excavation are increasing with the strength of the backfill material decreasing. When C15 and C40 concrete are used as backfill materials, the shield tunneling has no much effect on the surrounding rocks and geological stratum. C15 concrete is recommended as the backfill material for this project. It is highly risky that the large TBM directly drives the tunnel which is not backfilled after the small TBM tunneling. Ground settlement is insignificant when the buried depth ranges from 21 m to 45 m. But following the deepened buried depth, the ground stress increases significantly, and so does the stress of the tunnel structure.Tumor Hospital Metro Station on Shenzhen Metro Line 14 adopts the C15 concrete backfilling plan in the end, and the monitoring results of ground settlement is basically in line with the numerical simulation calculation.

Abstract Disease is a major concern in Porphyra aquaculture, particularly during the early shell-borne conchocelis (SBC) seedling stage. To explore prevention strategies for Porphyra diseases, this study explored the potential of using oligoagars (OA) and microbial agents (MA) to treat SBC of Neoporphyra haitanensis in an aquaculture environment. The impact of these treatments on the phycosphere microbial community was analyzed, and the resistance of the treated Porphyra conchocelis to the pathogenic bacterium Vibrio mediterranei 117-T6 (which causes yellow spot disease) was tested in the lab. Results showed that OA reduced α-diversity while enriching Rhodobacteriaceae, and MA increased stability and relative abundance of Bacteroidetes (including Flavobacteria). Furthermore, compared to the control group, the abundance of pathogenic microorganisms and virulence functional genes decreased while defense-related functional gene abundance increased significantly in the groups treated with OA and MA. Most importantly, the OA and MA treatments improved resistance to Vm117-T6, with survival rates of 70% (OA) and 80% (MA), compared to 15% in the control group. Overall, the findings suggest that OA and MA treatments have great potential for preventing Porphyra disease, as they improve phycosphere microorganisms and increase algae resistance to pathogenic bacteria.

ABSTRACTThe segmented negative-strand RNA viruses (sNSVs) include highly pathogenic human and animal viruses such as Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and influenza A virus (IAV). One of the conserved mechanisms at the stage of genome transcription of sNSVs is the cap-snatching process, providing druggable targets for the development of antivirals. SFTSV is an emerging tick-borne sNSV that causes severe hemorrhagic fever with a high fatality rate of 12%–50%. Here, we determined the correlation between death outcome and downregulation of the WNT-CTNNB1 signaling pathway through transcriptomic analysis of blood samples collected from SFTS patients. We further demonstrated that SFTSV affected this pathway by downregulating the mRNA levels of a series of pathway-related genes, including CTNNB1. Loss-of-function mutations or inhibitors targeting SFTSV cap-snatching activity effectively alleviated the inhibition of the WNT-CTNNB1 signaling pathway. Exogenous activation of the WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway reduced SFTSV replication. Treatment with a WNT-CTNNB1 signaling pathway inhibitor attenuated viral replication and decreased fatality in mice. Notably, downregulation of the WNT-CTNNB1 signaling pathway was also observed for other sNSVs, including LASV and IAV. These results suggested that RNAs related to the WNT-CTNNB1 signaling pathway might be utilized as a primer “pool” in a cap-snatching manner for viral transcription, which provides effective targets for the development of broad-spectrum antivirals against sNSVs.IMPORTANCEOne of the conserved mechanisms at the stage of genome transcription of segmented negative-strand RNA viruses (sNSVs) is the cap-snatching process, which is vital for sNSVs transcription and provides drugable targets for the development of antivirals. However, the specificity of RNAs snatched by sNSV is still unclear. By transcriptomics analysis of whole blood samples from SFTS patients, we found WNT-CTNNB1 signaling pathway was regulated according to the course of the disease. We then demonstrated that L protein of severe fever with thrombocytopenia syndrome virus (SFTSV) could interact with mRNAs of WNT-CTNNB1 signaling pathway-related gene, thus affecting WNT-CTNNB1 signaling pathway through its cap-snatching activity. Activation of WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway decreased SFTSV replication in vitro and in vivo. These findings suggest that WNT-associated genes may be the substrate for SFTSV “cap-snatching”, and indicate a conserved sNSVs replication mechanism involving WNT-CTNNB1 signaling.

Graphitic carbon nitride (g-C3N4) has attracted extensive research interest in pollutants remediation. However, the photocatalytic activity of g-C3N4 was significantly limited by its small specific surface area. In this work, a green, high-energy ball milling method was used to fabricate g-C3N4 nanosheets. The structure, morphology, and optical properties of the prepared g-C3N4 nanosheets were characterized. The effect of ball milling parameters on the photocatalytic performance evaluated by Rhodamine B (RhB) and tetracycline (TC) was investigated systemically. Among the tested samples, the g-C3N4 sample milled with a 4 mL isopropanol solution at a rotation speed of 420 rpm, ball-to-powder weight ratio of 10:1, and milling time of 24 h exhibited the highest RhB degradation efficiency of 91.4% and TC degradation efficiency of 70.2%. The enhanced photocatalytic activity after ball milling was ascribed to the increase in specific surface area and efficient separation of electron–hole pairs. The trapping experiment indicated that holes and superoxide radicals were the main active species in the degradation reaction. Moreover, the photocatalytic degradation mechanism of organic pollutants on g-C3N4 nanosheets was also discussed in detail.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6–9.5 μm in diameter, average diameter > 4.2 μm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.