Current status of high-risk HPV infection and correlation with multiple infections in cervical lesions in Western Guangzhou.

Objective: This study aims to investigate the current status of multiple HPV infection and its association with cervical lesions in the western region of Guangzhou. Methods: A retrospective analysis of clinical data from cervical cancer screening patients was conducted. The patients were grouped based on HPV genotypes and cervical pathology results to explore the prevalence of high-risk HPV infection and its relationship with cervical lesions in the western region of Guangzhou. The study also analyzed the relationship between high-risk HPV infection and cervical lesions among different age groups. Results: A total of 13,060 patients were included in the study, with an overall infection rate of 18.46% (2,411/13,060). Among them, the infection rate of HPV genotype 16 was 14.14% (341/2,411), HPV genotype 18 was 5.23% (126/2,411), and other 12 high-risk HPV genotypes accounted for 71.96% (1,735/2,411). When comparing the incidence of HSIL+ (high-grade squamous intraepithelial lesion or worse) among different HPV genotypes, the results showed that the HPV 16 infection group (47.50%) had a higher incidence than the HPV 18 infection group (25.40%) and the other 12 high-risk HPV genotypes group (15.97%; P < 0.05). In the multiple infection groups, the pathogenicity rates were 63.64% (7/11) for the 16+18 HPV infection group, 42.97% (55/128) for the 16+other 12 high-risk HPV genotypes infection group, 26.79% (15/56) for the 18+other 12 high-risk HPV genotypes infection group, and 57.14% (8/14) for the 16+18+other 12 high-risk HPV genotypes infection group. These rates were significantly different compared to the single infection group (P <0.01). Although there was no statistically significant difference in the incidence of cervical cancer between the HPV 16 infection group and the HPV 18 infection group, both groups had a higher incidence compared to the group with other 12 high-risk HPV genotypes infection (P < 0.05). Further analysis suggests that the severity of cervical lesions is not associated with the number of high-risk HPV infections, i.e., the severity of cervical lesions is unrelated to multiple HPV infections but is instead related to the pathogenicity of the HPV genotypes. The infection rate and multiple HPV infection rate of women under 35 years old were higher than those of women aged 35 and above (20% vs. 17.1%; 2% vs. 1.3%; P < 0.05). Moreover, the pathogenicity rate of HSIL+ among high-risk HPV infection increased with age. Conclusions: In the western region of Guangzhou, the overall infection rate of high-risk HPV is 18.46%. The severity of cervical lesions is unrelated to multiple HPV infections. The fundamental reason is the distinct pathogenicity of different HPV genotypes. The HSIL+ pathogenicity rates, from high to low, are in sequence for HPV 16, HPV 18, and the other 12 HPV types.

C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2'-O-methylation of PARP1.

BACKGROUND: Small nucleolar RNAs (snoRNAs) are dysregulated in many cancers, although their exact role in tumor genesis and progression remains unclear. METHODS: The expression profiles of snoRNAs in endometrial cancer (EC) tissues were analyzed using data from The Cancer Genome Atlas, and SNORD104 was identified as an upregulated snoRNA in EC. The tumorigenic role of SNORD104 in EC was established in CCK8, colony formation, EdU, apoptosis, Transwell, and in vivo xenograft experiments. The molecular mechanisms of SNORD104 were analyzed by RNA immunoprecipitation (RIP), Nm-seq, RTL-P assay, RNA stability assay, qRT-PCR, and western blotting. RESULTS: Antisense oligonucleotide (ASO)-mediated knockdown of SNORD104 in Ishikawa cells significantly inhibited their proliferation, colony formation ability, migration, and invasion in vitro and increased apoptosis. On the other hand, overexpression of SNORD104 promoted EC growth in vivo and in vitro. RIP assay showed that SNORD104 binds to the 2'-O-methyltransferase fibrillarin (FBL), and according to the results of Nm-seq and RTL-P assay, SNORD104 upregulated PARP1 (encoding poly (ADP-ribose) polymerase 1) 2'-O-methylation. The binding of FBL to PARP1 mRNA was also verified by RIP assay. Furthermore, SNORD104 expression was positively correlated with PARP1 expression in EC tissues. In the presence of actinomycin D, SNORD104 increased the stability of PARP1 mRNA and promoted its nuclear localization. Finally, silencing FBL or PARP1 in the HEC1B cells overexpressing SNORD104 inhibited their proliferative and clonal capacities and increased apoptosis rates. CONCLUSIONS: SNORD104 enhances PARP1 mRNA stability and translation in the EC cells by upregulating 2'-O-methylation and promotes tumor growth.

Small Nucleolar RNA and C/D Box 15B Regulate the TRIM25/P53 Complex to Promote the Development of Endometrial Cancer.

Background: Endometrial cancer is associated with a high mortality rate, which warrants the identification of novel diagnostic markers and therapeutic targets. The aim of this study is to evaluate the role of SNORD15B in the development of endometrial cancer and explore the potential underlying mechanisms. Methods: Bioinformatics was used to analyze the expression level and prognostic relevance of SNORD15B in endometrial cancer. The Ishikawa and HEC-1B cells were respectively transfected with SNORD15B expression plasmid and an antisense oligonucleotide, or the corresponding empty vector and a nonspecific sequence. The malignant phenotype of the suitably transfected cells was assessed by standard in vitro functional assays and the establishment of in vivo xenografts. The expression levels of the specific markers were analyzed with RT-qPCR and western blotting. The subcellular localization of P53 was determined by analyzing the nuclear and cytoplasmic fractions. RIP, Co-IP, and immunohistochemistry were performed as per standard protocols. Results: SNORD15B was overexpressed in the endometrial cancer tissues and correlated to a poor prognosis. Ectopic expression of SNORD15B in Ishikawa cells inhibited apoptosis, increased the proliferation, invasion, and migration in vitro, and enhanced their tumorigenicity in vivo. SNORD15B overexpression also upregulated TRIM25 and accelerated P53 accumulation in the cytoplasm of the endometrial cancer cells. Conclusion: SNORD15B functions as an oncogene in endometrial cancer by targeting the TRIM25/P53 complex and blocking the nuclear translocation of P53.

Insights into roles of METTL14 in tumors.

N6-Methyladenosine (m6A) is considered the most common and endogenous modification of eukaryotic RNAs. Highly conserved in many species, m6A regulates RNA metabolism, cell differentiation, cell circadian rhythm, and cell cycle; it also responds to endogenous and exogenous stimuli and is associated with the development of tumors. The m6A methyltransferase complex (MTC) regulates the m6A modification of transcripts and involves two components, methyltransferase-like enzyme 3 (METTL3) and methyltransferase-like enzyme 14 (METTL14), and other auxiliary regulatory distinct components. Though with no catalytic effect, METTL14 serves as an RNA-binding scaffold in MTC, promotes RNA substrate recognition, activates, and escalates the catalytic capability of METTL3, thus accounting for a pivotal member of the complex. It was reported that METTL14 regulates tumor proliferation, metastasis, and self-renewal, and plays a part in tumorigenesis, tumor progression, and other processes. The present work is a review of the role of METTL14 both as a tumor suppressor and a tumor promoter in the oncogenesis and progression of various tumors, as well as the potential molecular mechanisms.

Research progress on the tsRNA classification, function, and application in gynecological malignant tumors.

A large number of small non-coding RNAs derived from tRNAs, called tRNA-derived small RNA (tsRNAs), have been identified by high-throughput RNA sequencing of cell lines. Further research has revealed that they are not produced via random tRNA degradation, but through degradation by specific nuclease cleavages, such as Elac Ribonuclease Z 2 (ELAC2)/RNase Z, RNase L, Dicer, and angiogenin (ANG), the tsRNAs can be classified into the following types based on the location from which they have been derived from the parental tRNA: tRF-1s, tRF-3s, tRF-5s, tiRNA, and tRF-2s/i-tRFs. Moreover, tsRNAs are a type of small RNAs with diverse functions, including gene expression regulation, anti-apoptosis, translation inhibition, participation in epigenetic regulation, initial virus reverse transcription, promote virus replication and cell-to-cell communication. Certain types of tsRNAs are overexpressed in cancer tissues, but are underexpressed in normal tissues. Therefore, the relationship between tsRNAs and the occurrence and development of cancer has attracted significant research attention. Research advancements have contributed to further discoveries of the biological activities of tsRNAs, but the mechanisms of their biogenesis and functions have not been fully elucidated. This article reviews the classification and biological functions of tsRNAs, and introduces the research progress in gynecological malignancies.

Ambiguity of Residual Constraint-Based Precise Point Positioning with Partial Ambiguity Resolution under No Real-Time Network Corrections Using Real Global Positioning System (GPS) Data.

Although precise point positioning (PPP) is a well-established and promising technique with the use of precise satellite orbit and clock products, it costs a long convergence time to reach a centimeter-level positioning accuracy. The PPP with ambiguity resolution (PPP-AR) technique can improve convergence performance by resolving ambiguities after separating the fractional cycle bias (FCB). Now the FCB estimation is mainly realized by the regional or global operating reference station network. However, it does not work well in the areas where network resources are scarce. The contribution of this paper is to realize an ambiguity residual constraint-based PPP with partial ambiguity resolution (PPP-PARC) under no real-time network corrections to speed up the convergence, especially when the performance of the float solution is poor. More specifically, the update strategy of FCB estimation in a stand-alone receiver is proposed to realize the PPP-PAR. Thereafter, the solving process of FCB in a stand-alone receiver is summarized. Meanwhile, the influencing factors of the ambiguity success rate in the PPP-PAR without network corrections are analyzed. Meanwhile, the ambiguity residual constraint is added to adapt the particularity of the partial ambiguity-fixing without network corrections. Moreover, the positioning experiments with raw observation data at the Global Positioning System (GPS) globally distributed reference stations are conducted to determine the ambiguity residual threshold for post-processing and real-time scenarios. Finally, the positioning performance was verified by 22 GPS reference stations. The results show that convergence time is reduced by 15.8% and 26.4% in post-processing and real-time scenarios, respectively, when the float solution is unstable, compared with PPP using a float solution. However, if the float solution is stable, the PPP-PARC method has performance similar to the float solution. The method shows the significance of the PPP-PARC for future PPP applications in areas where network resource is deficient.

The Unified Form of Code Biases and Positioning Performance Analysis in Global Positioning System (GPS)/BeiDou Navigation Satellite System (BDS) Precise Point Positioning Using Real Triple-Frequency Data.

Multi- system and multi-frequency are two key factors that determine the performance of precise point positioning. Both multi-frequency and multi-system lead to new biases, which are not solved systematically. This paper concentrates on mathematical models of biases, influences of these biases, and positioning performance analysis of different observation models. The biases comprise the inter-frequency clock bias in multi-frequency and the inter-system clock bias in multi-system. The former is the residual differential code biases (DCBs) from receiver clock and satellite clock and usually occurs at the third frequency, the latter is the deviation of the receiver clock errors in different systems. Unified mathematical models of the biases are presented by analyzing the general formula of observation equations. The influences of these biases are validated by experiments with corresponding observation models. Subsequently, the experiments, which are based on the data at five globally distributed stations in Multi-Global Navigation Satellite System (GNSS) Experiment (MGEX) on day of year 100, 2018, assess positioning performance of different observation models with combination of frequencies (dual-frequency or triple- frequency) and systems (BeiDou Navigation Satellite System (BDS) or Global Positioning System (GPS)). The results show that the performances of triple-frequency models are almost as the same level as the dual-frequency models. They provide scientific support for the triple-frequency ambiguity-fixed solution which has a better convergence characteristic than dual-frequency ambiguity-fixed solution. Furthermore, the biases are expressed as an unified form that gives an important and valuable reference for future research on multi-frequency and multi-system precise point positioning.

A Joint Method Based on Time-Frequency Distribution to Detect Time-Varying Interferences for GNSS Receivers with a Single Antenna.

In this paper, a joint method combining Hough transform and reassigned smoothed pseudo Wigner-Ville distribution (RSPWVD) is presented to detect time-varying interferences with crossed frequency for a Global Navigation Satellite System (GNSS) receiver with a single antenna. The proposed method can prevent the cross-term interference and detect the time-varying interferences with crossed frequency which cannot be achieved by the classical time-frequency (TF) analysis with the peak detection method. The actual performance of the developed method has been evaluated by experiments with conditions where the real BeiDou system (BDS) B1I signals are corrupted by the simulated chirp interferences. The results of experiments show that the introduced method is effectively able to detect chirp interferences with crossed frequency and provide the same root mean square errors (RMSE) of the parameter estimation for chirp one and the improved initial frequency estimation for chirp two compared with the Hough transform of Wigner-Ville distribution (WVD) when the jamming to noise ratio (JNR) equals or surpasses 4 dB.

An Environmentally-Adaptive Positioning Method Based on Integration of GPS/DTMB/FM.

The Global Positioning System (GPS) yields good precision and availability in open outdoor environment. However, the errors of GPS may suffer degradation in some complex environments, such as forests and urban canyons. To solve this problem, a new positioning method is designed integrating GPS, Digital Terrestrial Multimedia Broadcast (DTMB) and frequency-modulated (FM) radio signal. In this method, the DTMB transmitter acts as a pseudo-satellite to assist GPS positioning. Furthermore, the FM fingerprint positioning is used to correct the positioning bias. An adaptive selection scheme is proposed to provide an optimal integration mode of the sensors. Field experiments in complex environment were carried out for evaluation. Comparing to the GPS-only and GPS + DTMB approach, positioning accuracy was improved by at least 68.21 % and 21.27 % with the proposed method, respectively.

Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose-Lock (MTLL) for GPS Receivers.

Frequency-locked detector (FLD) has been widely utilized in tracking loops of Global Positioning System (GPS) receivers to indicate their locking status. The relation between FLD and lock status has been seldom discussed. The traditional PLL experience is not suitable for FLL. In this paper, the threshold setting criteria for frequency-locked detector in the GPS receiver has been proposed by analyzing statistical characteristic of FLD output. The approximate probability distribution of frequency-locked detector is theoretically derived by using a statistical approach, which reveals the relationship between probabilities of frequency-locked detector and the carrier-to-noise ratio (C/N0) of the received GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection threshold and lock probability related to C/N0 can be further discovered by utilizing this probability. Therefore, a theoretical basis for threshold setting criteria in frequency locked loops for GPS receivers is provided based on mean-time-to-lose-lock analysis.

A Real-Time Interference Monitoring Technique for GNSS Based on a Twin Support Vector Machine Method.

Interferences can severely degrade the performance of Global Navigation Satellite System (GNSS) receivers. As the first step of GNSS any anti-interference measures, interference monitoring for GNSS is extremely essential and necessary. Since interference monitoring can be considered as a classification problem, a real-time interference monitoring technique based on Twin Support Vector Machine (TWSVM) is proposed in this paper. A TWSVM model is established, and TWSVM is solved by the Least Squares Twin Support Vector Machine (LSTWSVM) algorithm. The interference monitoring indicators are analyzed to extract features from the interfered GNSS signals. The experimental results show that the chosen observations can be used as the interference monitoring indicators. The interference monitoring performance of the proposed method is verified by using GPS L1 C/A code signal and being compared with that of standard SVM. The experimental results indicate that the TWSVM-based interference monitoring is much faster than the conventional SVM. Furthermore, the training time of TWSVM is on millisecond (ms) level and the monitoring time is on microsecond (µs) level, which make the proposed approach usable in practical interference monitoring applications.

A performance improvement method for low-cost land vehicle GPS/MEMS-INS attitude determination.

Global positioning system (GPS) technology is well suited for attitude determination. However, in land vehicle application, low-cost single frequency GPS receivers which have low measurement quality are often used, and external factors such as multipath and low satellite visibility in the densely built-up urban environment further degrade the quality of the GPS measurements. Due to the low-quality receivers used and the challenging urban environment, the success rate of the single epoch ambiguity resolution for dynamic attitude determination is usually quite low. In this paper, a micro-electro-mechanical system (MEMS)-inertial navigation system (INS)-aided ambiguity resolution method is proposed to improve the GPS attitude determination performance, which is particularly suitable for land vehicle attitude determination. First, the INS calculated baseline vector is augmented with the GPS carrier phase and code measurements. This improves the ambiguity dilution of precision (ADOP), resulting in better quality of the unconstrained float solution. Second, the undesirable float solutions caused by large measurement errors are further filtered and replaced using the INS-aided ambiguity function method (AFM). The fixed solutions are then obtained by the constrained least squares ambiguity decorrelation (CLAMBDA) algorithm. Finally, the GPS/MEMS-INS integration is realized by the use of a Kalman filter. Theoretical analysis of the ADOP is given and experimental results demonstrate that our proposed method can significantly improve the quality of the float ambiguity solution, leading to high success rate and better accuracy of attitude determination.