An Innovative Stent Consisting of Expanded Polytetrafluoroethylene and Ear Cartilage in Rhinoplasty For Asians: Application I of Dai's Exogenous Extension Stent Concept.

BACKGROUND: Restricted ventilation is common after rhinoplasty with an endogenous extension stent. The authors proposed an exogenous extension stent concept for Asian rhinoplasty patients to avoid this problem. Herein, we introduce an innovative stent in rhinoplasty for Asians, which is an application of this concept. METHODS: An L-shaped expanded polytetrafluoroethylene is hand-carved, and the long arm is placed at the nose back to improve the flatness of the nose, while the short arm supports the nasal column to raise the nose tip. The prosthesis does not occupy nasal volume and therefore theoretically does not affect nasal ventilation. The fan-shaped ear cartilage was placed at the nasal tip to prevent visualization of the nasal tip. The safety and effectiveness of this method were verified through 20 years of clinical practice. The difficulty of learning and popularizing the method was tested through the course of rhinoplasty among 22 plastic surgeons. RESULTS: After 20 years of clinical practice, it was found that this stent could not only effectively improve the nasal dorsum and tip morphology, but also did not actually affect the nasal volume and thus did not affect the nasal ventilation of patients. Among the trainees in plastic surgery, we found that it was not difficult to learn this method of rhinoplasty and the trainees could complete the prosthesis carving well after standardized training. CONCLUSION: This stent consisting of expanded polytetrafluoroethylene and ear cartilage is suitable in rhinoplasty for Asians with significant advantages, one of which is that it has no risk of resulting in restricted nasal ventilation. LEVEL OF EVIDENCE: Level IV.

Nasal Tip and Alar Groove Plasty Through External Nasal Cutting in Asians: A Clinical Study.

OBJECTIVE: Nasal tip hypertrophy is common in Asians, and its reshaping is very critical in rhinoplasty. For patients who refuse any implant placed in the nose, there are limited options for tip reshaping. Herein, we introduce a new procedure of nasal tip and alar groove plasty through external nasal cutting in Asians. METHODS: A total of 20 patients who had hypertrophic nasal tip and refused to have any implants were included in this study. They were performed this procedure of nasal tip and alar groove plasty through external nasal cutting. The authors carefully reviewed the patients' medical records and preoperative and postoperative photographs. Self-reported satisfactions of patients with the scar morphology and correction effect were assessed at postoperative every follow-up using a questionnaire survey. RESULTS: All of the patients' procedures were completely successful, and the hypertrophic nasal tip was improved. In the long-term postoperative follow-up, the patients' wound showed no abnormalities such as scar contracture deformity, scar bumps, and nasal deformation. In 1 patient, the nasal wound developed significant scarring, and we performed reoperation to remove the superficial scar tissue. Surgical scars in the remaining patients were not obvious. Eight patients (8/20) reported "very satisfied" with scar shape and nasal tip shape improvement results, and 10 patients (10/20) reported "satisfied" with the outcomes. CONCLUSIONS: This procedure of nasal tip and alar groove plasty could be an alternative for making the nasal tip more refined. However, the surgical indications for this procedure need to be strictly limited to specific patients. LEVEL OF EVIDENCE: Level IV.

Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.

Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-ß promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-ß promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-ß1 and IL6 promoters. The specific regulation of SPHK2 on IFN-ß promoter through TET3 can in turn recruit HDAC1 to the IFN-ß promoter, enhancing the deacetylation of IFN-ß promoter, therefore leading to the inhibition of IFN-ß transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.

Phylogenetic Implication of Large Intergenic Spacers: Insights from a Mitogenomic Comparison of Prosopocoilus Stag Beetles (Coleoptera: Lucanidae).

To explore the characteristics of mitogenomes and discuss the phylogenetic relationships within the genus Prosopocoilus, the mitogenomes of two species (P. castaneus and P. laterotarsus) were newly sequenced and comparatively analyzed. The arrangement of the mitogenome in these two lucanid beetles was the same as that in the inferred ancestral insect, and the nucleotide composition was highly biased towards A + T as in other lucanids. The evolutionary rates of 13 protein-coding genes (PCGs) suggested that their evolution was based on purifying selection. Notably, we found evidence of the presence of a large IGS between trnI and trnQ genes, whose length varied from 375 bp (in P. castaneus) to 158 bp (in P. laterotarsus). Within the large IGS region, a short sequence (TAAAA) was found to be unique among these two species, providing insights into phylogenomic reconstruction. Phylogenetic analyses were performed using the maximum likelihood (IQ-TREE) and Bayesian (PhyloBayes) methods based on 13 protein-coding genes (PCGs) in nucleotides and amino acids (AA) from published mitogenomes (n = 29). The genus Prosopocoilus was found to constitute a distinct clade with high nodal support. Overall, our findings suggested that analysis of the characteristics of the large IGS (presence or absence, size, and location) in mitogenomes of the genus Prosopocoilus may be informative for the phylogenetic and taxonomic analyses and for evaluation of the genus Prosopocoilus, despite the dense sampling materials needed.

Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus.

Lytic replication of human cytomegalovirus (HCMV), a member of ß-herpesvirus, is a highly complicated and organized process that requires its DNA polymerase processivity factor, UL44, the first-reported HCMV replication protein subjected to SUMO post-translational modification (PTM). SUMOylation plays a pleiotropic role in protein functions of host cells and infecting viruses. Particularly, formation of herpesviral replication compartments (RCs) upon infection is induced in proximity to ND10 subnuclear domains, the host cell's intrinsic antiviral immune devices and hot SUMOylation spots, relying just on SUMOylation of their protein components to become mature and functional in restriction of the viral replication. In this study, to unveil the exact role of SUMO PTM on UL44 involved in HCMV replication, we screened and identified PIAS3, an annotated E3 SUMO ligase, as a novel UL44-interacting protein engaged in cellular SUMOylation pathway. Co-existence of PIAS3 could enhance the UBC9-based SUMO modification of UL44 specifically at its conserved 410lysine residue lying within the single canonical ψKxE SUMO Conjugation Motif (SCM). Intriguingly, we found this SCM-specific SUMOylation contributes to UL44 co-localization and interaction with subnuclear ND10 domains during infection, which in turn exerts an inhibitory effect on HCMV replication and growth. Together, these results highlight the importance of SUMOylation in regulating viral protein subnuclear localization, representing a novel way of utilizing ND10-based restriction to achieve the self-controlled slower replication and reproduction of herpesviruses.

PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor.

Influenza A virus (IAV) utilizes multiple strategies to confront or evade host type I interferon (IFN)-mediated antiviral responses in order to enhance its own propagation within the host. One such strategy is to induce the degradation of type I IFN receptor 1 (IFNAR1) by utilizing viral hemagglutinin (HA). However, the molecular mechanism behind this process is poorly understood. Here, we report that a cellular protein, poly(ADP-ribose) polymerase 1 (PARP1), plays a critical role in mediating IAV HA-induced degradation of IFNAR1. We identified PARP1 as an interacting partner for IAV HA through mass spectrometry analysis. This interaction was confirmed by coimmunoprecipitation analyses. Furthermore, confocal fluorescence microscopy showed altered localization of endogenous PARP1 upon transient IAV HA expression or during IAV infection. Knockdown or inhibition of PARP1 rescued IFNAR1 levels upon IAV infection or HA expression, exemplifying the importance of PARP1 for IAV-induced reduction of IFNAR1. Notably, PARP1 was crucial for the robust replication of IAV, which was associated with regulation of the type I IFN receptor signaling pathway. These results indicate that PARP1 promotes IAV replication by controlling viral HA-induced degradation of host type I IFN receptor. Altogether, these findings provide novel insight into interactions between influenza virus and the host innate immune response and reveal a new function for PARP1 during influenza virus infection.IMPORTANCE Influenza A virus (IAV) infections cause seasonal and pandemic influenza outbreaks, which pose a devastating global health concern. Despite the availability of antivirals against influenza, new IAV strains continue to persist by overcoming the therapeutics. Therefore, much emphasis in the field is placed on identifying new therapeutic targets that can more effectively control influenza. IAV utilizes several tactics to evade host innate immunity, which include the evasion of antiviral type I interferon (IFN) responses. Degradation of type I IFN receptor (IFNAR) is one known method of subversion, but the molecular mechanism for IFNAR downregulation during IAV infection remains unclear. Here, we have found that a host protein, poly(ADP-ribose) polymerase 1 (PARP1), facilitates IFNAR degradation and accelerates IAV replication. The findings reveal a novel cellular target for the potential development of antivirals against influenza, as well as expand our base of knowledge regarding interactions between influenza and the host innate immunity.

Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences.

External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA. In MCMV-infected cells, the variant reduced mCSP expression by 92% and inhibited viral growth by 8,000-fold. In MCMV-infected mice hydrodynamically transfected with EGS-expressing constructs, the EGS variant was more effective in reducing mCSP expression, decreasing viral production, and enhancing animal survival than the EGS originating from a natural tRNA. These results provide direct evidence that engineered EGS variants with higher targeting activity in vitro are also more effective in reducing gene expression in animals. Furthermore, our findings imply the possibility of engineering potent EGS variants for therapy of viral infections.