METTL1-mediated m7G modification of Arg-TCT tRNA drives oncogenic transformation.

The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m7G) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. Mechanistically, we find increased abundance of m7G-modified tRNAs, in particular Arg-TCT-4-1, and increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon. Accordingly, Arg-TCT expression is elevated in many tumor types and is associated with patient survival, and strikingly, overexpression of this individual tRNA induces oncogenic transformation. Thus, METTL1-mediated tRNA modification drives oncogenic transformation through a remodeling of the mRNA "translatome" to increase expression of growth-promoting proteins and represents a promising anti-cancer target.

Structural basis for impaired 5' processing of a mutant tRNA associated with defects in neuronal homeostasis.

SignificanceUnderstanding and treating neurological disorders are global priorities. Some of these diseases are engendered by mutations that cause defects in the cellular synthesis of transfer RNAs (tRNAs), which function as adapter molecules that translate messenger RNAs into proteins. During tRNA biogenesis, ribonuclease P catalyzes removal of the transcribed sequence upstream of the mature tRNA. Here, we focus on a cytoplasmic tRNAArgUCU that is expressed specifically in neurons and, when harboring a particular point mutation, contributes to neurodegeneration in mice. Our results suggest that this mutation favors stable alternative structures that are not cleaved by mouse ribonuclease P and motivate a paradigm that may help to understand the molecular basis for disease-associated mutations in other tRNAs.

The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017-2023.

Cervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People's Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers.

Nonlinear relationship between viral load and TCT in single/multiple HPV52 infection.

PURPOSE: To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. METHODS: A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. RESULTS: In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. CONCLUSION: HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Optimising cervical cancer screening during pregnancy: a study of liquid-based cytology and HPV DNA co-test.

This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low-grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P < 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.

1,3,5-Triazine as Branching Connector for the Construction of Novel Antimicrobial Peptide Dendrimers: Synthesis and Biological Characterization.

Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we have addressed dendrimers, attractive molecules in pharmaceutical innovation and development displaying broad biological activity. Triazine-based dendrimers were fully synthesized in the solid phase, and their antimicrobial activity and some insights into their mechanisms of action were explored. Triazine is present in a large number of compounds with highly diverse biological targets with broad biological activities and could be an excellent branching unit to accommodate peptides. Our results show that the novel peptide dendrimers synthesized have remarkable antimicrobial activity against Gram-negative bacteria (E. coli and P. aeruginosa) and suggest that they may be useful in neutralizing the effect of efflux machinery on resistance.

Exploring the Interpad Gap Region in Ultra-Fast Silicon Detectors: Insights into Isolation Structure and Electric Field Effects on Charge Multiplication.

We present an in-depth investigation of the interpad (IP) gap region in the ultra-fast silicon detector (UFSD) Type 10, utilizing a femtosecond laser beam and the transient current technique (TCT) as probing instruments. The sensor, fabricated in the trench-isolated TI-LGAD RD50 production batch at the FBK Foundry, enables a direct comparison between TI-LGAD and standard UFSD structures. This research aims to elucidate the isolation structure in the IP region and measure the IP distance between pads, comparing it to the nominal value provided by the vendor. Our findings reveal an unexpectedly strong signal induced near p-stops. This effect is amplified with increasing laser power, suggesting significant avalanche multiplication, and is also observed at moderate laser intensity and high HV bias. This investigation contributes valuable insights into the IP region's isolation structure and electric field effects on charge collection, providing critical data for the development of advanced sensor technology for the Compact Muon Selenoid (CMS) experiment and other high-precision applications.

TRF2, but not TBP, mediates the transcription of ribosomal protein genes.

The TCT core promoter element is present in most ribosomal protein (RP) genes in Drosophila and humans. Here we show that TBP (TATA box-binding protein)-related factor TRF2, but not TBP, is required for transcription of the TCT-dependent RP genes. In cells, TCT-dependent transcription, but not TATA-dependent transcription, increases or decreases upon overexpression or depletion of TRF2. In vitro, purified TRF2 activates TCT but not TATA promoters. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) experiments revealed the preferential localization of TRF2 at TCT versus TATA promoters. Hence, a specialized TRF2-based RNA polymerase II system functions in the synthesis of RPs and complements the RNA polymerase I and III systems.

Automatic model for cervical cancer screening based on convolutional neural network: a retrospective, multicohort, multicenter study.

BACKGROUND: The incidence rates of cervical cancer in developing countries have been steeply increasing while the medical resources for prevention, detection, and treatment are still quite limited. Computer-based deep learning methods can achieve high-accuracy fast cancer screening. Such methods can lead to early diagnosis, effective treatment, and hopefully successful prevention of cervical cancer. In this work, we seek to construct a robust deep convolutional neural network (DCNN) model that can assist pathologists in screening cervical cancer. METHODS: ThinPrep cytologic test (TCT) images diagnosed by pathologists from many collaborating hospitals in different regions were collected. The images were divided into a training dataset (13,775 images), validation dataset (2301 images), and test dataset (408,030 images from 290 scanned copies) for training and effect evaluation of a faster region convolutional neural network (Faster R-CNN) system. RESULTS: The sensitivity and specificity of the proposed cervical cancer screening system was 99.4 and 34.8%, respectively, with an area under the curve (AUC) of 0.67. The model could also distinguish between negative and positive cells. The sensitivity values of the atypical squamous cells of undetermined significance (ASCUS), the low-grade squamous intraepithelial lesion (LSIL), and the high-grade squamous intraepithelial lesions (HSIL) were 89.3, 71.5, and 73.9%, respectively. This system could quickly classify the images and generate a test report in about 3 minutes. Hence, the system can reduce the burden on the pathologists and saves them valuable time to analyze more complex cases. CONCLUSIONS: In our study, a CNN-based TCT cervical-cancer screening model was established through a retrospective study of multicenter TCT images. This model shows improved speed and accuracy for cervical cancer screening, and helps overcome the shortage of medical resources required for cervical cancer screening.

Severe cervical inflammation and high-grade squamous intraepithelial lesions: a cross-sectional study.

PURPOSE: Inflammation has been reported as a facilitator in cervical oncogenesis, but the correlation between inflammation and cytological abnormality remains uncertain. The aim of this study was to investigate the correlation between inflammation and cytological abnormality. METHODS: ThinPrep cytological test (TCT) was used to detect cervical cytological abnormalities and inflammation degrees of 46,255 women in this prospective cross-sectional study. Histopathological examination was used to define the cervical intraepithelial neoplasia (CIN) in patients with cervical cytological abnormalities. RESULTS: The study revealed that 8.87% (4102/46,255) of TCT results had cytological abnormalities. The 4102 included cases were classified as the case group, including atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Women with negative intraepithelial lesion or malignancy (NILM) were classified as the control group. About 88.83% (3644/4102) of women with cytological abnormalities showed inflammations. The rate of severe inflammation was significantly higher in the case group than the control group (23.86% vs. 2.0%, P = 0.000). Our results also showed that patients with severe inflammation had a significantly increasing incidence of cytological abnormality by 12.598 times and elevated the risk of HSIL by 756.47 times, compared to the inflammation negative group. CONCLUSION: Severe inflammation was positively related to HSIL. Patients with severe cervical inflammation should be given more follow-ups and regular examinations and treated more carefully than those with mild or no inflammation.

Trauma CT evaluation prior to selective angiography in patients with traumatic injuries: negative predictive power and factors affecting its utility.

PURPOSE: To evaluate the predictive power of arterial injury detected on contrast-enhanced CT (trauma CT (tCT)) imaging obtained prior to selective angiography for treatment of patients with traumatic abdominal and pelvic injuries. MATERIALS AND METHODS: A retrospective chart review was performed of all patients who underwent angiography after undergoing contrast-enhanced CT imaging for the evaluation/treatment of traumatic injuries to the abdomen and pelvis between March 2014 and September 2018. Data collection included demographics, pertinent history and physical findings, CT and angiography findings, treatment information, and outcomes. RESULTS: Eighty-nine (63 males, mean age = 45.8 ± 20.5 years) patients that were found to have 102 traumatic injuries on tCT and subsequently underwent angiography met inclusion criteria for this study. Sixty-four injuries demonstrated evidence of traumatic vascular injury on initial tCT. A negative tCT was able to predict subsequent negative angiography in 83% of cases (negative predictive power = 83%). The ability of tCT to rule out a positive finding on subsequent angiography was also 83% (sensitivity = 83%). The average systolic blood pressure and hemoglobin concentration at the time of tCT were higher in patients who had positive tCT than in patients with negative tCT (p < 0.05 and p < 0.01, respectively). The average time to angiography was greater in patients whom had subsequent negative angiography than the patients who had subsequent positive angiography (p < 0.05). CONCLUSION: Contrast-enhanced CT imaging may be able to help stratify patients who may have subsequent negative angiograms. Hemodynamic factors may affect sensitivity of tCT. Shorter time to angiography may increase the chance of identifying the injury on subsequent angiography.

The clinical research of Thinprep Cytology Test (TCT) combined with HPV-DNA detection in screening cervical cancer.

Our objective is to explore the clinical value of thinprep cytologic test (TCT) combined with HPV-DNA detection in screening cervical cancer. 420 cervical cancer patients admitted in our hospital between April, 2011-April, 2014 were selected. All patients received TCT and HPV-DNA detection, and cervical tissue biopsy was used to confirm the diagnosis. TCT screening results showed that there were 175 patients were >ASCUS and the positive rate was 41.7%, histopathological screening showed that there were 199 patients were ≥cervical intraepithelial neoplasia (CIN) I and the positive rate was 47.4%. HPV-DNA detection showed 180 patients were positive which was 42.9%, and the positive rate of HPV-DNA detection was increased as the disease severity increased. The sensitivity of TCT combined with HPV-DNA detection was higher than single TCT or HPV-DNA, however the specificity was relatively low, and the positive predictive value and negative predictive value were higher which were similar to pathological results. TCT combined with HPV-DNA detection has high sensitivity and accuracy in screening cervical cancer, which is worthy of clinical application.

Cervical Infection of Oncogenic Human Papillomavirus (HPV) Types in Beijing, China.

OBJECTIVE: This study was designed to determine the prevalence of oncogenic human papillomavirus (HPV) in cervical infections in Beijing, China, and to investigate the odds ratio (OR) of HPV single and multiple infections in abnormal cytology. METHODS: A total of 19,018 specimens from outpatients in the department of obstetric and gynecology were collected. They were detected using high-risk HPV genotyping real-time polymerase chain reaction (PCR) kit and analyzed by ThinPrep cytology test for cervical pathological diagnosis. HPV prevalence, age-specific prevalence, and OR of each type of HPV in abnormal cytology were analyzed. RESULTS: Overall, 19.1% (3,623/19,018) of the individuals were positive for HPV infection, 14.9% (2,833/19,018) were positive for a single HPV type, and 4.2% (790/19,018) were positive for multiple types. Among the 3,623 HPV-positive individuals, the most predominant HPV types were HPV52 (4.4%, 834/19,018), HPV16 (3.7%, 710/19,018), and HPV58 (3.4%, 644/19,018). The OR of multiple infections and single infection differed significantly among disease severities. The OR of dual infection was higher than that of each of the two single infection types, respectively. CONCLUSION: HPV prevalence in the outpatients was 19.1%, and the most predominant HPV types in the study were HPV52, HPV16, and HPV58. Women with multiple infectionswere more likely to have abnormal cytology.

American Society for Transplantation and Cellular Therapy International Affairs Committee: Report of the 4th Workshop on Quality as a Development Tool for Hematopoietic Cell Transplantation Programs at the 2023 Tandem BMT Meetings.

We provide a summary of the 4th ASTCT International Workshop with presentations from experts from Chile ("Setting Up a Transplantation Program in Chile," by Dr Pablo Ramirez), Saudi Arabia ("Developing Quality Programs in North Africa," by Dr Amal Alseraihy), and Japan ("The Japanese Transplant Registry Unified Management Program [TRUMP]: Current Issues and the Future," by Dr Yoshiko Atsuta). Workshop objectives included: (1) recognizing the benefits and importance for low- and middle-income countries of developing quality criteria and programs beyond existing accreditation programs, such as the Foundation for the Accreditation of Cellular Therapy (FACT) and the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE); (2) describing the relationships among monitoring outcomes, including mortality, improvement of care, data reporting, and associated costs; and (3) reviewing how quality structures have been implemented and are improving care worldwide.

International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the number of HCTs performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pretransplantation, peritransplantation, and post-transplantation exposures and other underlying risk factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and then updated in 2012. An international group of experts was convened to review the contemporary literature and update the recommendations while considering the changing practices of HCT and cellular therapy. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed, but cGVHD management is not covered in detail. These guidelines emphasize the special needs of patients with distinct underlying HCT indications or comorbidities (eg, hemoglobinopathies, older adults) but do not replace more detailed group-, disease-, or condition-specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

HPV E6/E7 mRNA combined with thin-prep cytology test for the diagnosis of residual/recurrence after loop electrosurgical excision procedure in patients with cervical intraepithelial neoplasia.

To evaluate the diagnostic value of combining HPV E6/E7 mRNA testing with Thin-Prep cytology (TCT) for residual/recurrence detection, a total of 289 patients who underwent loop electrosurgical excision procedure (LEEP) for high-grade cervical lesions were included. Patients were followed up at different time points, and residual/recurrent lesions were confirmed through vaginoscopy. TCT, HPV-DNA, and HPV E6/E7 mRNA tests were conducted. Diagnostic performance, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, was assessed. Among the patients, 76 cases showed residual lesions/recurrence, while 213 cases showed no residual/recurrence. Positive margins in the cervical-vaginal and cervical canal areas were associated with a higher risk of residual/recurrence. The combined HPV E6/E7 mRNA and TCT test showed higher diagnostic efficacy than individual tests at 6-, 12-, and 24-months follow-up. The combined test consistently demonstrated higher specificity and sensitivity, with significantly larger area under the curve (AUC) values compared to the individual tests.

Mild and efficient cyanuric chloride catalyzed Pictet-Spengler reaction.

A practical, mild and efficient protocol for the Pictet-Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet-Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet-Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet-Spengler reaction.

Is Negative Affect that Bad? The Effect of Affective States on Conventional and Unconventional Creative Thinking in University Students.

Introduction: The role of affective states on the creative process has been receiving the attention of researchers and has led to contradictory results. Most research in creativity has emphasized the role of affective states, mainly positive ones, on creativity levels, namely those resulting from divergent thinking tasks that reveal the unconventional way of thinking in the creative process. However, there are no studies to date that focus on the impact of affective states on conventional and unconventional thinking, during the same creative process, which consider a single creative assessment task. The aim of this experimental study was to analyze the effect of induced affective states on both conventional and unconventional thinking of creativity in adults by using the TCT-DP (Test for Creative Thinking-Drawing Production). Method: Seventy-five university students, mostly female, with a mean age of 26.95 years, were randomly assigned into three affect elicitation conditions (pleasant vs. unpleasant vs. neutral). Results: Results indicated that the negative affective state led to higher levels of conventional thinking when compared to positive and neutral affective states. However, no significant differences were found on unconventional thinking across the three conditions. Conclusions: Our results do not support the assumption that the negative affect has a hindering effect on creativity nor the positive affect increases creativity. Negative affect seems to promote conventional thinking, perhaps due to its cognitive correlates, which can be manifested in focusing attention and analytic thinking. Practical and theoretical implications for future research on the role of affective states on creativity are discussed.

Introducción: El papel de los estados afectivos en el proceso creativo ha sido objeto de atención por parte de los investigadores y ha dado lugar a resultados contradictorios. La mayor parte de la investigación en creatividad ha hecho hincapié en el papel de los estados afectivos, principalmente los positivos, sobre los niveles de creatividad. A saber, los resultantes de las tareas de pensamiento divergente que revelan la forma no convencional de pensar en el proceso creativo. Este estudio tuvo como objetivo analizar el efecto de los estados afectivos inducidos en dos dimensiones distintas del pensamiento creativo en adultos. Método: Setenta y cinco voluntarios, en su mayoría mujeres, con una edad media de 26.95 años, fueron asignados aleatoriamente a tres condiciones de elicitación de estados afectivos (agradable vs desagradable vs neutral), justo antes de realizar una tarea de creatividad figurativa. Resultados: Los resultados indicaron que el estado afectivo negativo condujo a niveles más altos de pensamiento convencional. Conclusiones: Nuestros resultados no apoyan ni la hipótesis de que el afecto negativo tiene un efecto perjudicial sobre la creatividad ni la de que el afecto positivo aumenta la creatividad. El afecto negativo parece promover el pensamiento convencional, quizá debido a sus correlatos cognitivos, que pueden manifestarse en la atención focalizada y el pensamiento analítico. Se discuten las implicaciones prácticas y teóricas para futuras investigaciones sobre el papel de los estados afectivos en la creatividad.

Research of cervical microbiota alterations with human papillomavirus infection status and women age in Sanmenxia area of China.

Background: Human papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China. Materials and methods: In this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out. Results: The major microbiota compositions of all patients include Lactobacillus iners, Escherichia coli, Enterococcus faecalis, and Atopobium vaginae at species level, and Staphylococcus, Lactobacillus, Gardnerella, Bosea, Streptococcus, and Sneathia in genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869, p < 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885, p < 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337, p = 0.1012), other1 (94.9619, p < 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851, p < 0.01, n = 255) than younger women (87.0171, n = 21). The abundance of Gardnerella and Atopobium vaginae was significantly higher in the HPV-positive group than in the HPV-negative group, while Burkholderiaceae and Mycoplasma were more abundant in the unique-268 group compared to the negative group. Gamma-proteobacteria and Pseudomonas were found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups. Conclusion: The HPV infection status and age of women were related to CM's diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.