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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]

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(NO3)3 to induce an aqueous‐phase chain reaction generating free CO32− ions with subsequent instant FeCO3 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. [ABSTRACT FROM AUTHOR]

In hyperspectral images, endmembers characterizing one class of ground object may vary due to illumination, weathering, slight variations of the materials. This phenomenon is called intra-class endmember variability which is one of the important factors affecting the performance of unmixing. However, intra-class endmember variability is often ignored in unmixing, which causes a decrease in the accuracy of unmixing. How to deal with intra-class endmember variability is the focus. To address this problem, we propose a novel hyperspectral unmixing method based on Least Squares Twin Support Vector Machines (ULSTWSVM). ULSTWSVM uses multiple training samples (endmembers) to model a pure class, which takes intra-class endmember variability into account in unmixing. At the same time, ULSTWSVM obtains abundances by calculating the distances from the mixed pixels to the classification hyperplanes, which is simple and efficient. ULSTWSVM mainly comprises three steps: (1) to obtain the two non-parallel classification hyperplanes by solving two quadratic programming problems (QPPs) in least squares sense, (2) to calculate distances from the mixed pixels to classification hyperplanes, and (3) to normalize the distances and convert them to abundances. Experimental results on both synthetic and real hyperspectral data show that the proposed method outperforms the methods used for comparison. [ABSTRACT FROM AUTHOR]