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Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. A total of 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease. [ABSTRACT FROM AUTHOR]

This study aims to characterize the genetic variability of HPV58, identify novel lineages and sublineages, and explore the association between persistent/multiple HPV58 infections and genetic variation. In this study, samples from 124 women with HPV58 infection in Eastern China were collected and 81 isolates of E6 and L1 full‐length genes were successfully amplified from 55 samples. We evaluated the diversity of genetic variants and performed correlation analyses between genetic variability and pathology, vaccination, multiple infections, and persistent infections. Among the E6 and L1 gene sequences collected, the dominant prevailing sublineages were A1 (46.2%) and A2 (23.1%). In addition, we found two potential novel sublineages denoted as the A4 and A5 sublineage. A total of 50 nucleotide substitutions, including 28 synonymous substitutions and 22 nonsynonymous substitutions, were observed in the E6 and L1 genes. Among them, variants with A388C/K93N substitutions in the E6 gene correlated with persistent infection (≥1 and ≥2 years) (p < 0.005), and C307T/C66C was associated with persistent infection (≥2 years) (p < 0.005). Notably, two mutations above were detected in the isolate from the patient with breakthrough vaccine infection. Our study found two novel sublineages and sites of genetic variability in multiple and persistent infection variants. In addition, we identified two mutational sites associated with persistent infection. This study provides new insight into the clinical characteristics of HPV 58 genetic variations and offers new ideas for research on next‐generation vaccines in Eastern China. [ABSTRACT FROM AUTHOR]

Purpose: To identify the bibliometric information of Human papillomavirus (HPV) genotype co-infection in certain literature database over the past two decades., Methods: Web of Science was used as the main database to identify all eligible articles focusing on HPV genotype co-infection at the date of October 16, 2022. From this journal database, we identified 463 articles on HPV genotype co-infection, conducted statistical analysis according to the author, journal, publication year and month, country or region, keyword and impact factor., Results: The articles included in our analysis were published between 1994 and 2022. The index of citations per year ranged from 170.4 to 13.1. These articles were from 78 countries or regions, with most publications from the United States (n = 73), followed by China (n = 65) and Italy (n = 50). The journal that contributed the most publications on HPV heterotypic gene co-infection was PLOS ONE with a total of 29 articles, followed by JOURNAL OF MEDICAL VIROLOGY (n = 28), INFECTIOUS AGENTS AND CANCER (n = 14) and JOURNAL OF CLINICAL VIROLOGY (n = 12). Among existing research in the field of HPV co-infection, we found that epidemiological distribution and infection mechanism has been the two major topics for scholars, and studies on detection methods for HPV multiple genotypes were also included., Conclusion: Over decades, epidemiological studies and mechanism investigationhas been the central topics when it comes to HPV genotypes co-infection. Studies on HPV co-infection remained relatively insufficient, mainly stays in qualitative level while detailed infection data and high quality literature publications were still lack of valuable discussion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bi, Gong, Mo, Wang, Qu, Wang, Shi, Zhang, Sui and Li.)

Combining the self-sacrifice of a highly crystalline substance to design a multistep chain reaction towards ultrathin active-layer construction for high-performance water splitting with atmospheric-temperature conditions and an environmentally benign aqueous environment is extremely intriguing and full of challenges. Here, taking cobalt carbonate hydroxides (CCHs) as the initial crystalline material, we choose the Lewis acid metal salt of Fe(NO 3 ) 3 to induce an aqueous-phase chain reaction generating free CO 3 2- ions with subsequent instant FeCO 3 hydrolysis. The resultant ultrathin (∼5 nm) amorphous Fe-based hydroxide layer on CCH results in considerable activity in catalyzing the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), yielding 10/50 mA ⋅ cm -2 at overpotentials of 230/266.5 mV for OER and 72.5/197.5 mV for HER. The catalysts can operate constantly in 1.0 M KOH over 48 and 45 h for the OER and HER, respectively. For bifunctional catalysis for alkaline electrolyzer assembly, a cell voltage as low as 1.53 V was necessary to yield 10 mA cm -2 (1.7 V at 50 mA cm -2 ). This work rationally builds high-efficiency electrochemical bifunctional water-splitting catalysts and offers a trial in establishing a controllable nanolevel ultrathin lattice disorder layer through an atmospheric-temperature chemical route., (© 2022 Wiley-VCH GmbH.)