Heat-Shock Protein 90 Promotes Nuclear Transport of Herpes Simplex Virus 1 Capsid Protein by Interacting with Acetylated Tubulin

Although it is known that inhibitors of heat shock protein 90 (Hsp90) can inhibit herpes simplex virus type 1 (HSV-1) infection, the role of Hsp90 in HSV-1 entry and the antiviral mechanisms of Hsp90 inhibitors remain unclear. In this study, we found that Hsp90 inhibitors have potent antiviral activity against standard or drug-resistant HSV-1 strains and viral gene and protein synthesis are inhibited in an early phase. More detailed studies demonstrated that Hsp90 is upregulated by virus entry and it interacts with virus. Hsp90 knockdown by siRNA or treatment with Hsp90 inhibitors significantly inhibited the nuclear transport of viral capsid protein (ICP5) at the early stage of HSV-1 infection. In contrast, overexpression of Hsp90 restored the nuclear transport that was prevented by the Hsp90 inhibitors, suggesting that Hsp90 is required for nuclear transport of viral capsid protein. Furthermore, HSV-1 infection enhanced acetylation of α-tubulin and Hsp90 interacted with the acetylated α-tubulin, which is suppressed by Hsp90 inhibition. These results demonstrate that Hsp90, by interacting with acetylated α-tubulin, plays a crucial role in viral capsid protein nuclear transport and may provide novel insight into the role of Hsp90 in HSV-1 infection and offer a promising strategy to overcome drug-resistance

Retracted Article: Binding Mechanism of Aviation Wire Harness Based on Improved Particle Swarm Optimization

We, the Editor and Publisher of Applied Artificial Intelligence, have retracted the following article:Zhang Maoyun, Xi Huizhuang, Tang Chen, Jiang Yuheng, Zhang Ziyan & Tian Chunlin, Binding Mechanism of Aviation Wire Harness Based on Improved Particle Swarm Optimization, Applied Artificial Intelligence https://doi.org/10.1080/08839514.2024.2327009Since publication, concerns have been raised by the authors about the integrity of the data presented in the article. The authors have identified issues with the programming statistics that have led to conclusions which are not credible and have requested the retraction of the article.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”

Identification and validation of autophagy-related genes in SSc

Multiple organs are affected by the complex autoimmune illness known as systemic sclerosis (SSc), which has a high fatality rate. Genes linked to autophagy have been linked to the aetiology of SSc. It is yet unknown, though, whether autophagy-related genes play a role in the aetiology of SSc. After using bioinformatics techniques to examine two databases (the GSE76885 and GSE95065 datasets) and autophagy-related genes, we were able to identify 12 autophagy-related differentially expressed genes that are linked to the pathophysiology of SSc. Additional examination of the receiver operating characteristic curve revealed that SFRP4 (AUC = 0.944, P < 0.001) and CD93 (AUC = 0.904, P < 0.001) might be utilized as trustworthy biomarkers for the diagnosis of SSc. The SSc group’s considerably greater CD93 and SFRP4 expression levels compared to the control group were further confirmed by qRT-PCR results. The autophagy-related genes SFRP4 and CD93 were found to be viable diagnostic indicators in this investigation. Our research sheds light on the processes by which genes linked to autophagy affect the pathophysiology of SSc

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

Vascular calcification is strongly associated with atherosclerotic plaque burden and plaque instability. The activation of extracellular signal-regulated kinase 1/2 (ERK1/2) increases runt related transcription factor 2 (RUNX2) expression to promote vascular calcification. Procyanidin B2 (PB2), a potent antioxidant, can inhibit ERK1/2 activation in human aortic smooth muscle cells (HASMCs). However, the effects and involved mechanisms of PB2 on atherosclerotic calcification remain unknown. In current study, we fed apoE-deficient (apoE−/−) mice a high-fat diet (HFD) while treating the animals with PB2 for 18 weeks. At the end of the study, we collected blood and aorta samples to determine atherosclerosis and vascular calcification. We found PB2 treatment decreased lesions in en face aorta, thoracic, and abdominal aortas by 21.4, 24.6, and 33.5%, respectively, and reduced sinus lesions in the aortic root by 17.1%. PB2 also increased α-smooth muscle actin expression and collagen content in lesion areas. In the aortic root, PB2 reduced atherosclerotic calcification areas by 75.8%. In vitro, PB2 inhibited inorganic phosphate-induced osteogenesis in HASMCs and aortic rings. Mechanistically, the expression of bone morphogenetic protein 2 and RUNX2 were markedly downregulated by PB2 treatment. Additionally, PB2 inhibited ERK1/2 phosphorylation in the aortic root plaques of apoE−/− mice and calcified HASMCs. Reciprocally, the activation of ERK1/2 phosphorylation by C2-MEK1-mut or epidermal growth factor can partially restore the PB2-inhibited RUNX2 expression or HASMC calcification. In conclusion, our study demonstrates that PB2 inhibits vascular calcification through the inactivation of the ERK1/2-RUNX2 pathway. Our study also suggests that PB2 can be a potential option for vascular calcification treatment

Characterization of the complete chloroplast genome sequence of Chinese endemic species of Nouelia insignis (Hyalideae, Asteraceae) and its phylogenetic implications

This study was the first report complete chloroplast genome of Nouelia insignis (Asteraceae, Hyalideae), the large shrubs to small trees endemic to China. The circular whole cp genome of N. insignis was 151,524 bp in length, containing a large single-copy (LSC) region of 83,145 bp and a small single-copy (SSC) region of 18,261 bp. These two regions were separated by a pair of inverted repeat regions (IRa and IRb), each of them 25,060 bp in length. A total of 135 functional genes were encoded, consisting of 89 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The overall GC content of the chloroplast genome sequence was 37.8%, and the GC contents of the LSC, SSC, and IR regions were 35.9, 31.5, and 43.2%, respectively. The phylogenetic analysis by the Bayesian analysis showed that the species of N. insignis was sister group with Gerbera jamesonii by strong support values, and thus was closely related to members of subfamilies of Cichorioideae and Pertyoideae. These results will be useful for the future studies of Asteraceae in the worldwide

Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.

Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs) against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18) and VP5 (UL19) individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1

Hsp90 plays a crucial role in ICP5 nuclear translocation.

<p>(A) Confocal images show capsid protein transport reduced by Hsp90 inhibition. MRC-5 cells exposed to HSV-1 (MOI = 10) for 4 h under the treatment of Hsp90 inhibitor (0.8 µM) were stained for ICP5 (red), total Hsp90 (green), and nuclei (blue). (B) Hsp90 is important for capsid protein nuclear transport. Cell monolayers infected with HSV-1 (MOI = 10) for different times were stained for ICP5 (red), total Hsp90 (green), and nuclei (blue). Five images per dish were acquired by LSM for counting of ICP5 docked in nuclear. The percentage of positive nuclei (nuclei with ICP5) was calculated. Each value represents the mean ± SD of three independent experiments (**, <i>P</i><0.01, compared with the viral control. ^##, <i>P</i><0.01, compared with the BJ-B11-treated group).</p