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Percutaneous abdominal puncture is a popular interventional method for the management of abdominal tumors. Image-guided puncture can help interventional radiologists improve targeting accuracy. The second generation of Kinect™ was released recently, we developed an optical navigation system to investigate its feasibility for guiding percutaneous abdominal puncture, and compare its performance on needle insertion guidance with that of the first-generation Kinect™. For physical-to-image registration in this system, two surfaces extracted from preoperative CT and intraoperative Kinect™ depth images were matched using an iterative closest point (ICP) algorithm. A 2D shape image-based correspondence searching algorithm was proposed for generating a close initial position before ICP matching. Evaluation experiments were conducted on an abdominal phantom and six beagles in vivo. For phantom study, a two-factor experiment was designed to evaluate the effect of the operator’s skill and trajectory on target positioning error (TPE). A total of 36 needle punctures were tested on a Kinect™ for Windows version 2 (Kinect™ V2). The target registration error (TRE), user error, and TPE are 4.26  ±  1.94 mm, 2.92  ±  1.67 mm, and 5.23  ±  2.29 mm, respectively. No statistically significant differences in TPE regarding operator’s skill and trajectory are observed. Additionally, a Kinect™ for Windows version 1 (Kinect™ V1) was tested with 12 insertions, and the TRE evaluated with the Kinect™ V1 is statistically significantly larger than that with the Kinect™ V2. For the animal experiment, fifteen artificial liver tumors were inserted guided by the navigation system. The TPE was evaluated as 6.40  ±  2.72 mm, and its lateral and longitudinal component were 4.30  ±  2.51 mm and 3.80  ±  3.11 mm, respectively. This study demonstrates that the navigation accuracy of the proposed system is acceptable, and that the second generation Kinect™-based navigation is superior to the first-generation Kinect™, and has potential of clinical application in percutaneous abdominal puncture. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. Methods: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-bystep debulking MWA (n ¼ 52) or continued TACE (n ¼ 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. Results: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. Conclusion: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. [ABSTRACT FROM AUTHOR]

We report the isolation of Tamdy virus from Hyalomma asiaticum ticks in northwest China and serologic evidence of human Tamdy virus infection in the same region. These findings highlight the need to further investigate a potential causal relationship between Tamdy virus and febrile illnesses of unknown etiology in that region. [ABSTRACT FROM AUTHOR]

The bromoalkane, 1-bromopropane (1-BP), may damage the reproductive system though oxidative stress, while the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in regulating intracellular antioxidant levels against oxidative stress. This study explored the role of oxidative stress and the Nrf2 signaling pathway in mediating the reproductive toxicity of 1-BP using the ovarian carcinoma cell line OVCAR-3 as an in vitro model of the human ovary. OVCAR-3 cells were treated with 1, 5, 10 and 15 mM 1-BP. After 24 h, the cellular reactive oxygen species and malondialdehyde concentrations significantly increased, while the superoxide dismutase activity decreased; translocation of Nrf2 from the cytosol to the nucleus as well as downstream protein expression of Nrf2-regulated genes heme oxygenase-1 and Bcl-2 was inhibited. Apoptosis was also observed, accompanied by increased caspase-3 and caspase-9 activity. The antioxidant vitamin C alleviated 1-BP-induced apoptosis by inhibiting caspase activity activating the Nrf2 signaling pathway. These findings suggested that 1-BP induced oxidative stress and apoptosis in OVCAR-3 cells through inactivation of Nrf2 signaling. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2- Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2- Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats. [ABSTRACT FROM AUTHOR]

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma (EC) has not been analyzed yet. Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor (ER), insulin receptor (InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin. Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-ß and IRS-1, whereas insulin significantly induced phosphorylation of ER-a. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-ß inhibition had a limited effect on estradiol-dependent proliferation, cell cycle, and apoptosis, whereas ER-a inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice. Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-ß and ER-a, promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways. [ABSTRACT FROM AUTHOR]

Ferromagnetism in half-metallic two-dimensional materials can lead to unique spintronics applications. Here we report first-principles calculations that predict monolayer graphyne nanoribbons (GyNRs), an alternative to graphene, doped randomly with 3d-series transition metal atoms at medium-to-high concentrations (2%-5%) can be ferromagnetic (FM). Furthermore, Mn- and Co-doped GyNRs are half-metallic with 100% spin polarization at the Fermi level and can act as perfect spin filters. The high spin polarization of the current is preserved up to large bias voltages. This study provides a basis for the fabrication of GyNRs with ferromagnetism and spin-polarized electron transport properties. [ABSTRACT FROM AUTHOR]

Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease. [ABSTRACT FROM AUTHOR]

An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln226) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu226). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu226 → Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property. [ABSTRACT FROM AUTHOR]

Interspecies transmission (host switching/jumping) of influenza viruses is a key scientific question that must be addressed. In addition to the vigorous research on highly pathogenic avian influenza viruses (HPAIVs), studies of the mechanism of interspecies transmission of low-pathogenic avian influenza viruses (LPAIVs) could also provide insights into host tropism and virulence evolution. Influenza A viruses harboring hemagglutinin (HA) H13 (e.g., H13N6) are LPAIVs. In this study, soluble H13 HA glycoprotein was purified, and its receptor binding activity was characterized. The results revealed that H13 exclusively binds the avian a2-3-linked sialic acid receptor; no binding to the mammalian a2-6-linked sialic acid receptor was detected. Furthermore, the molecular basis of the H13 receptor binding specificity was revealed by comparative analysis of the crystal structures of both receptor-bound H13 and H5 HAs, which might be contributed by the hydrophobic residue V186. Work with an H13N186 mutant confirmed the importance of V186 in the receptor binding specificity of H13 HA, which shows that the mutant protein reduced the binding of an avian receptor analog but increased the binding of a human receptor analog. Detailed structural analysis also demonstrated that the conserved binding sites of the recently well-studied broadly neutralizing human monoclonal antibodies targeting the HA2 domain are found in H13. Our results expand our understanding of virulence evolution, receptor binding preference, and species tropism of the LPAIVs and HPAIVs. [ABSTRACT FROM AUTHOR]