Seagrass decline weakens sediment organic carbon stability.

Seagrass meadows are globally recognized as critical natural carbon sinks, commonly known as 'blue carbon'. However, seagrass decline attributed to escalating human activities and climate change, significantly influences their carbon sequestration capacity. A key aspect in comprehending the impact of seagrass decline on carbon sequestration is understanding how degradation affects the stored blue carbon, primarily consisting of sediment organic carbon (SOC). While it is widely acknowledged that seagrass decline affects the input of organic carbon, little is known about its impact on SOC pool stability. To address this knowledge, we examined variations in total SOC and recalcitrant SOC (RSOC) at a depth of 15 cm in nine seagrass meadows located on the coast of Southern China. Our findings revealed that the ratio of RSOC to SOC (RSOC/SOC) ranged from 27 % to 91 % in the seagrass meadows, and the RSOC/SOC increased slightly with depth. Comparing different seagrass species, we observed that SOC and RSOC stocks were 1.94 and 3.19-fold higher under Halophila beccarii and Halophila ovalis meadows compared to Thalassia hemprichii and Enhalus acoroides meadows. Redundancy and correlation analyses indicated that SOC and RSOC content and stock, as well as the RSOC/SOC ratio, decreased with declining seagrass shoot density, biomass, and coverage. This implies that the loss of seagrass, caused by human activities and climate change, results in a reduction in carbon sequestration stability. Further, the RSOC decreased by 15 %, 29 %, and 40 % under unvegetated areas compared to adjacent Halophila spp., T. hemprichii and E. acoroides meadows, respectively. Given the anticipated acceleration of seagrass decline due to climate change and increasing coastal development, our study provides timely information for developing coastal carbon protection strategies. These strategies should focus on preserving seagrass and restoring damaged seagrass meadows, to maximize their carbon sequestration capacity.

Plant growth and development of tropical seagrass determined rhizodeposition and its related microbial community.

In the recent study, we investigated the seasonal variations in root exudation and microbial community structure in the rhizosphere of seagrass Enhalus acoroides in the South China Sea. We found that the quantity and quality of root exudates varied seasonally, with higher exudation rates and more bioavailable dissolved organic matter (DOM) during the seedling and vegetative stages in spring and summer. Using Illumina NovaSeq sequencing, we analyzed bacterial and fungal communities and discovered that microbial diversity and composition were influenced by root exudate characteristics s and seagrass biomass, which were strongly dependent on seagrass growth stages. Certain bacterial groups, such as Ruegeria, Sulfurovum, Photobacterium, and Ralstonia were closely associated with root exudation and may contribute to sulfur cycling, nitrogen fixation, and carbon remineralization, which were important for plant early development. Similarly, specific fungal taxa, including Astraeus, Alternaria, Rocella, and Tomentella, were enriched in spring and summer and showed growth-promoting abilities. Overall, our study suggests that seagrass secretes different compounds in its exudates at various developmental stages, shaping the rhizosphere microbial assemblages.

Application an internet facilitation in a community-based cervical cancer screening project.

OBJECTIVE: To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. METHOD: A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25-60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. RESULTS: A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. CONCLUSION: When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Changes in surface sediment carbon compositions in response to tropical seagrass meadow restoration.

Seagrass meadows are declining at a global scale, threatening their capacity as blue carbon sinks. Restoration of seagrasses (via seagrass seeds or plant transplantation) may recover their carbon sequestration capacity. Previous studies have predominantly focused on sediment organic carbon (SOC), while variations in sediment carbon compositions remain poorly understood, limiting our comprehension of the influence of seagrass restoration on sediment carbon stability. Here, we researched the differences in surface (0-3 cm) sediment carbon compositions in response to tropical seagrass transplantation among species (Thalassia hemprichii and Enhalus acoroides); specifically, differences in labile, recalcitrant and refractory SOC, as well as sediment inorganic carbon (SIC) compositions variations under transplanted T. hemprichii and E. acoroides communities. It was found that seagrass transplantation enhanced suspended particle organic matter, and epiphyte and macroalgae input to surface sediment, which recovered the surface SOC concentration and stock rapidly to natural levels (increased ∼1.6-fold) within two years following transplantation. The elevated contribution of epiphyte and macroalgae significantly increased the surface labile sediment organic matter (SOM), but not the recalcitrant and refractory SOM composition after short-term transplantation. Meanwhile, surface SIC was significantly elevated, which might be mainly ascribed to allochthonous carbonate particle trapped under transplanted area with implications for carbon sequestration. The higher canopy and longer leaf seagrass species, E. acoroides, had elevated SOC, SIC and was more labile composition, compared to T. hemprichii transplant. Overall, this research suggests that tropical seagrass transplantation can increase the surface SOC, SIC concentration by increasing the labile organic matter and allochthonous carbonate particle input, respectively, with varying significantly among seagrass species.

Comprehensive profile and contrastive analysis of circular RNA expression in cervical squamous carcinoma and adenocarcinoma.

Background: Numerous studies have shown circular RNA (circRNA) dysregulation is associated with the pathogenesis of cervical cancer,particularly in individual carcinoma variants. The aim of this study is to investigate and contrastively analyze the expression pattern of circRNAs in cervical squamous carcinoma and adenocarcinoma mediated by human papillomavirus type 16 (HPV-16). Methods: The expression of circRNAs in cervical squamous carcinoma (SCC), adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) tissues, together with the adjacent normal tissues (ANT), was profiled by high-throughput RNA sequencing (RNA-seq). Bioinformatics analysis and quantitative real time polymerase chain reaction (qRT-PCR) validation of the sequencing data were performed. A network of circRNA-miRNA (microRNA)-mRNA was then constructed according to predicted targets and function of candidate circRNAs. Results: A total of 11,685 annotated circRNAs were identified in six cervical samples. There were 42 up-regulated and 98 down-regulated circRNAs. 215 circRNAs were up-regulated in SCC but down-regulated circRNAs in ADC, while 50 circRNAs displayed the opposite trend. Function enrichment analysis based on different expressions of circRNAs found that the most enriched pathway in all the three pathologic variants of cervical cancer was the "ubiquitin mediated proteolysis" pathway. Eight key candidate circRNAs derived from this pathway were further validated, and we noticed that several target miRNAs of candidate circRNAs could target the source genes. Based on this we constructed a related competing endogenous RNA (ceRNA) network. Conclusion: Through a comprehensive interpretation of differentially expressed circRNAs in different pathologic variants of cervical cancer, this study provides new insights into the process of tumor differentiation mediated by HPV. Our results may help to complement the molecular typing and stem cell theory of cervical cancer.

Prevalence of Human Papillomavirus Among Chinese Han and Mongols Minority Women in Inner Mongolia, China: Reflected by Self-Collected Samples in CHIMUST.

Background: The disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia. Methods: Genotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results. Results: The hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,-52,-18/-58,-31/-39, and-59 while in Mongols were-16,-31,-58,-18 and-52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40-44 (20.5%) and 55-59 (23.5%) years in Han women while three peaks were observed at age of 30-34 (22.1%), 45-49 (22.9%), and 55-59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively. Conclusion: The prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

Nano-AgCu Alloy on Wood Surface for Mold Resistance.

The mold infection of wood reduces the quality of its surface and potentially endangers human health. One category of the most popular mold inhibitors on the market is water-soluble fungicides. However, easy leaching due to ionic forms is a problem, which reduces the effectiveness of their antimicrobial action, as well as causing environmental pollution. Interestingly, nanometer-sized sterilizing agents present strong permeability and highly fungicidal behavior, and they are not easily leached, due to the unique nanoscale effect, and they have become alternative candidates as marketable anti-mold agents for wood protection. In this study, we first designed and explored a nanoscale alloy (nano silver-copper alloy, nano-AgCu) to treat wood surfaces for mold growth resistance. The results showed that three molds, i.e., Aspergillus niger, Penicillium citrinum and Trichoderma viride, mainly grew on the surface of wood within a depth of 100 µm; and that the nano-AgCu alloy with a particle size of ~15 nm presented improved retention and anti-mold efficiency at a nanomaterial concentration on the wood surface. Its leaching rate increased non-linearly with the increase in nano-AgCu retention and then it showed a gradually decreasing trend. When the concentration reached 1000 mg/L, the nano-AgCu alloy uniformly distributed on the wood surface in a monodispersed state and exhibited a lower retention of 0.342 g/m2, with an anti-mold efficiency of more than 75% and a leaching rate of only 7.678%. Such results positioned 1000 mg/L as the toxic threshold concentration of nano-AgCu against the three molds. This study can provide a scientific basis for the analysis of the anti-mold mechanisms of nano-AgCu alloy on wood surfaces and guide the application of nano-metal alloy materials in the field of wood antimicrobials.

Nutrient loading decreases blue carbon by mediating fungi activities within seagrass meadows.

Coastal pollution, including nutrient loading, can negatively impact seagrass health and cover and may consequently alter soil organic carbon (SOC) accumulation and preservation. Key to understanding how eutrophication impacts SOC cycling in seagrass ecosystems is how nutrient loading changes the sources of carbon being deposited and how these changes in resources, both nutrients and carbon availability, influence soil microbiota community and activity. Currently, the direction and magnitude of nutrient loading impacts on seagrass SOC dynamics are poorly understood at a meadow scale, limiting our ability to reveal the driving mechanisms of SOC remineralisation. The purpose of this study was to assess the response of surface SOC and soil microbiomes to nutrient loading within tropical seagrass meadows. To achieve this, we quantified both total SOC and recalcitrant soil organic carbon (RSOC) concentrations and sources, in addition to the composition of bacterial and fungal communities and soil extracellular enzyme activities. We found that nutrient loading elevated SOC and RSOC content, mainly facilitated by enhanced algal growth. There was no nutrient effect on the soil prokaryotic communities, however, saprotrophic fungi groups (i.e. Trapeliales, Sordaridales, Saccharomycetales and Polyporales) and fungal activities were elevated under high nutrient conditions, including extracellular enzyme activities linked to seagrass-based cellulose and lignin decomposition. This relative increase in RSOC transformation may decrease the relative contribution of seagrass carbon to RSOC pools. Additionally, significantly different fungal communities were observed between adjacent T. hemprichii and E. acoroides areas, which coincided with elevated RSOC-decomposing enzyme activity in T. hemprichii meadows, even though the mixed seagrass meadow received allochthonous SOC and RSOC from the same sources. These results suggest that nutrient loading stimulated fungal activity and community shifts specific to the local seagrass species, thereby causing fine-scale (within-meadow) variability in SOC cycling in response to nutrient loading. This study provides evidence that fungal composition and activity, mediated by human activities (e.g. nutrient loading), can be an important influence on seagrass blue carbon accumulation and remineralisation.

Leachability and Anti-Mold Efficiency of Nanosilver on Poplar Wood Surface.

Water-based antimicrobial agents, used in environmentally friendly applications, are widely used in wood protection industries. Furthermore, nanomaterials as antimicrobial agents, because of their biocidal component, huge specific surface area, and unique nanoscale effect, have attracted attention in the field of biodurability. We employed aqueous dispersed nano-silver with a diameter of 10 nm~20 nm to treat poplar wood and evaluated its leaching resistance and anti-mold effect on the wood surface. The results revealed that the higher the retention of the nano-silver, the stronger the protection efficiency of the wood surface against three molds (Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr); and the leachability of the nano-silver presented a slowly growing trend with the increase in the retention. When the wood surface attained a silver retention of 0.324 g·m-2, its anti-mold efficiency against Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr reached 80, 75, and 80%, respectively, which achieved or even exceeded the required standard value of effective mold inhibition (75%). Notably, the nano-silver leaching rate at this retention attained merely 4.75 %. The nanoparticle, well distributed on a wood surface, may promote sufficient contact with fungi as well as strong interaction with wood cell wall components, which probably contributed to the effective anti-mold efficiency and the leaching resistance. This study provided positive evidence for the anti-mold effect of nano-silver on wood surface.

The role of PAX1 methylation in predicting the pathological upgrade of cervical intraepithelial neoplasia before cold knife conization.

Objective: To explore the ability of PAX1 methylation (PAX1m) to predict the pathological upgrade of cervical intraepithelial neoplasia (CIN) before cold knife conization (CKC). Methods: A total of 218 women that underwent colposcopy-directed biopsy (CDB) pathology for the confirmation of CIN2 and CIN3 between December 2020 to September 2021 were enrolled in this study. The methylation levels of PAX1 (ΔCpPAX1) were determined by quantitative methylation-specific polymerase chain reaction (qMSP). Receiver operating characteristic curve was used to identify the optimal cut-off value of ΔCpPAX1 for predicting the pathological upgrade of disease. Results: In the CDB-confirmed CIN2 group, 36% of CIN2 was found to have pathologically upgraded to CIN3 and 30% regressed to low-grade squamous intraepithelial lesion (LSIL) and below, and none of CIN2 upgraded to early-stage cervical cancer (ESCC) after CKC. In the CDB-confirmed CIN3 group, 19.5% (23/118) of CDB-confirmed CIN3 were pathologically upgraded to ESCC after CKC. Regardless of CIN2 or CIN3, the ΔCpPAX1 level of women with upgraded pathology after CKC was significantly lower than that of women with degraded pathology. The optimal △CpPAX1 cut-off value in predicting CIN3 to be upgraded to ESCC after CKC was 6.360 and the area under the curve (AUC) was 0.814, with similar sensitivity (78.3%) and higher specificity (84.2%) than cytology≥LSIL (Se:78.3%;Sp:58.9%) and HPV16/18 positive (Se:73.9%;Sp:46.3%) patients. Conclusions: PAX1m could be a promising auxiliary marker in predicting the pathological upgrade of CIN before CKC. We found that if the △Cp PAX1 cut-off value is lower than 6.360, it is highly suggestive of invasive cervical cancer.

The prevalence of HR-HPV infection based on self-sampling among women in China exhibited some unique epidemiologic features.

Objective To investigate the epidemiological characteristics of high-risk human papillomavirus(HR-HPV) infection based on vaginal self-collected samples. Study Design and Setting The pooled data of 3045 self-collected samples used for the analysis derived from four previous studies on cervical cancer screening(The Chinese Multi-Center Screening Trial, CHIMUST; The Shenzhen Cervical Cancer Screening Trial-2, SHENCCAST-2; The Chinese Cervical Cancer Prevention Study, CHIPCAPS; Pingshan trial, PINGSHAN)conducted across China by our team since 2011. These cases were evaluated for HR-HPV type prevalence relative to lesion grade and age. The occurrence of cervical intraepithelial neoplasia(CIN) with specific HPV types and the influence of co-infection is explored. Results The top three most common genotypes among the HR-HPV positives were HPV-52(23.4%), HPV-16(18.0%), and HPV-58(15.50%). For women with CIN2+, the most frequent genotypes were HPV-16, 58, 52, and 18 in sequence. HPV-16 accounted for the majority of CIN2/CIN3/Ca with attribution rate of 23.86%, 44.78% and 50.00% respectively. HPV-58 accounted for 19.48%, 16.79% and 13.46% respectively. CIN2+ was found in the following types most frequently: HPV-16(31.23%), HPV-33(24.03%), HPV-58(18.41%), HPV-31(11.76%), HPV-18(7.75%), and HPV-52(7.30%). HPV-16 showed preference for co-infection with HPV-52 and HPV-58. Conclusion The prevalence of HR-HPV infection based on self-sampling among women in China exhibited some unique epidemiologic features.

[Spatial Distribution Characteristics, Source Apportionment, and Risk Assessment of Topsoil PAHs in the Core Area of the Ningdong Energy and Chemical Industry Base].

In order to evaluate the pollution of polycyclic aromatic hydrocarbons (PAHs) in the topsoil of the core area of the Ningdong Energy and Chemical Industry Base, 146 representative topsoil samples were collected using the grid method and the contents of 16 priority PAHs were analyzed. The results showed that the content of ΣPAHs in topsoil ranged from ND to 123.12 mg·kg-1 with an average of 10.19 mg·kg-1. There were three high PAHs distribution areas in the northwest, southwest, and east of the core area. The source apportionment showed that the sources of PAHs in the Ningdong base were complex, and the main pollution sources were petroleum, coal combustion, traffic, and gasoline, which contributed 39.4%, 33.3%, 19.2%, and 8.1% to the total PAHs sources, respectively. The ecological risk assessment of the quality basis and quality standard method showed that the ecological impact of PAHs in the core area was slight and the possibility of negative ecological effects was low. The results of the health risk assessment showed that the order of exposure of the topsoil PAHs was skin contact > swallowing > respiratory inhalation, and the topsoil PAHs in the core area of the Ningdong base posed no potential carcinogenic risk to people of different ages.

Evaluation of Cobas HPV and SeqHPV Assays in the Chinese Multicenter Screening Trial.

OBJECTIVE: The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST). MATERIALS AND METHODS: The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30-59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies. RESULTS: A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05). CONCLUSIONS: Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.

An evaluation of solid versus liquid transport media for high-risk HPV detection and cervical cancer screening on self-collected specimens.

BACKGROUND: The solid transport media is a small size card that allows fast, easy DNA extraction from a variety of biological samples. In 2016 we developed a solid media transport card; for that pilot study to control the self-collection we used a pseudo-self-collection technique. The current study expands this prior work using true self-collections and only the POI card, and aims to evaluate the solid media transport card to detect HR-HPV in self-samples compared to liquid transport media. METHODS: Ten thousand eight hundred eighty-five women between the ages of 30-59 with no screening for 3 years were enrolled. The self-collected sample was first applied to a new solid media transport card (Labeled as SC) then the brush placed in 6 ml ThinPrep liquid (Labeled as SL). Then a physician collected a direct endocervical specimen into ThinPrep liquid (Labeled as DL). Samples were tested with Cobas 4800 and the SeqHPV NGS assay for HR-HPV. Patients positive on any test were recalled for colposcopy and biopsy. RESULTS: Ten thousand three hundred thirty-nine participants had complete data. The mean age was 43.9 years. CIN 2+ rates were 1.4% (142/10339). The agreement in HPV detection between the two different self-sample collection media was also good (Cobas HPV kappa = 0.86; SeqHPV kappa = 0.98). Tested with Cobas, the sensitivity of Cobas-SL and Cobas-SC for CIN 2+ was95.07 and 94.37%; and for CIN3+ was 96.30, 96.30% respectively. The specificity of Cobas-SC, and Cobas-SL for CIN2+ was 88.74 and 87.35%; for CIN3 was 88.04and 86.65% respectively. Tested with SeqHPV, the sensitivity for CIN2+ of Seq-SC and Seq-SL was 95.77 and 96.48%; for CIN3+, both the SC and SL specimens had a sensitivity of 100%. The specificity for CIN2+ of Seq-SC and Seq-SL was 89.54 and 89.53%; for CIN3+ was 88.84,88.82% respectively. For both HR-HPV assays, the sensitivities were similar for the two self-sample media (SC vs SL, p = 1.00). CONCLUSIONS: The solid transport card for collecting vaginal self-samples as accurate as liquid transport media assayed by two different PCR based HR-HPV tests. The solid transport media is a suitable medium for collecting and storing vaginal self-samples.

Evaluation of alternately combining HPV viral load and 16/18 genotyping in secondary screening algorithms.

BACKGROUND: Correlation with HPV viral load and worsening cervical lesions had been reported, but its potential for triage after primary HPV screening has not been adequately explored, especially when combined with HPV-16/18 genotyping. OBJECTIVE: To evaluate combinations of human papillomavirus (HPV) viral load and genotyping for HPV-16/18 as secondary screening strategies. METHODS: The Shenzhen Cervical Cancer Screening Trial Ⅱ (SHENCCAST Ⅱ) database was re-analyzed to explore new screening algorithms using the results of Hybrid Capture 2 (HC2), Mass Array Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass spectrometry System (MALDI-TOF-MS) and the ThinPrep cytologic test (TCT) obtained by endocervical sampling. RESULTS: Compared with the recommended screening strategy of genotyping HPV-16/18 plus reflex to cytology, using viral load (10 RLU/CO as threshold) plus reflex to cytology resulted in less cytology but had a significantly higher sensitivity for cervical intraepithelial neoplasia 2+ (CIN2+)/CIN3+ without considerable changes in specificity and referral rates. Both of the strategy of using viral load ≥10 RLU/CO as cut-point for immediate colposcopy followed by triage genotyping HPV-16/18 for the other positive (≥1<10 RLU/CO) and the strategy of referring HPV-16/18 positives for immediate colposcopy followed by triage viral load (10 RLU/CO as threshold) for non-HPV-16/18 positives had comparable screening efficacy with algorithims that contain cytology. CONCLUSIONS: Primary HPV screening with triage of HPV-positive women by a combination of viral load and genotyping for HPV-16/18 provides good balance between sensitivity and specificity, the number of tests required, and referral rates.

Rpph1 Upregulates CDC42 Expression and Promotes Hippocampal Neuron Dendritic Spine Formation by Competing with miR-330-5p.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. Recent studies employing microRNA-seq and genome-wide sequencing have identified some non-coding RNAs that are influentially involved in AD pathogenesis. Non-coding RNAs can compete with other endogenous RNAs by microRNA response elements (MREs) and manipulate biological processes, such as tumorigenesis. However, only a few non-coding RNAs have been reported in the pathogenesis of AD. In this study, we constructed the first competing endogenous RNA (ceRNA) network leveraging whole transcriptome sequencing and a previously studied microRNA-seq of APPswe/PS1ΔE9 transgenic mice. The underlying mechanisms for the involvement of ceRNA in AD were validated using the Dual Luciferase Reporter Assay, detection of transcription levels by quantitative RT-PCR and translation levels by Western blotting, and morphological examination in primary cultured neurons. In the ceRNA network, four lncRNAs (C030034L19Rik, Rpph1, A830012C17Rik, and Gm15477) and five miRNAs (miR-182-5p, miR-330-5p, miR-326-3p, miR-132-3p, and miR-484) are enriched in nine pathways and an AD-related gene pool. Among them, Ribonuclease P RNA component H1 (Rpph1) is upregulated in the cortex of APPswe/PS1ΔE9 mice compared to wild type controls. Rpph1 binds to miR326-3p/miR-330-5p and causes the release of their downstream target Cdc42, which leads to CDC42 upregulation. This effect was disrupted upon mutation of the MRE on Rpph1. Moreover, overexpression of Rpph1 increased dendritic spine density in primary cultured hippocampal pyramidal neurons, whereas knocking down of Rpph1 had the reverse effect. In conclusion, Rpph1 modulates CDC42 expression level in a ceRNA-dependent manner, which may represent a compensatory mechanism in the early stage of the AD pathogenesis.

Evaluation of Viral Load as a Triage Strategy With Primary High-Risk Human Papillomavirus Cervical Cancer Screening.

OBJECTIVE: The aim of the study was to evaluate the human papillomavirus (HPV) viral load combined with cytology as a secondary screening strategy after primary HPV screening. MATERIALS AND METHODS: The data referring to direct Hybrid Capture 2 (HC2), cytology, and histology from Shenzhen Cervical Cancer Screening Trial II were re-analyzed to determine the correlation between viral load and cervical lesions. In addition, algorithms using different viral loads as cut points for immediate colposcopy plus cytology triage were compared with several recommended or controversial primary screening methods. RESULTS: A total of 8,556 women with a mean age of 38.9 years were included in the analysis, of which 13.67% tested high-risk HPV positive with a prevalence of 2.72% for cervical intraepithelial neoplasia 2+ (CIN 2+) and 1.65% for CIN 3+. A significant correlation was observed between increasing relative light units/control (RLU/CO) values and worsening cervical lesions. The mean RLU/CO values for negative, CIN 1, CIN 2, CIN 3, and cancer were 6.86, 119.43, 410.90, 449.39, and 853.26, respectively. A larger proportion of HPV infections with relative high viral load (≥10 RLU/CO) were found in higher-grade lesions. The algorithm using 10 or greater RLU/CO as cut point for immediate colposcopy followed by triage cytology for the other positive (≥1 < 10 RLU/CO) had sensitivity of 93.13%/96.45% and specificity of 92.32%/91.44% for CIN 2+/3+, and the colposcopy referral rate was 10.00%. CONCLUSIONS: Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.

Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related irreversible neurodegenerative disorder characterized by extracellular ß Amyloid(Aß) deposition, intracellular neurofibrillary tangles and neuronal loss. The dysfunction of neurogenesis and increased degeneration of neurons contribute to the pathogenesis of AD. We now report that miR-211-5p, a small non-coding RNA, can impair neurite differentiation by directly targeting NUAK1, decrease neuronal viability and accelerate the progression of Aß-induced pathologies. In this study, we observed that during embryonic development, the expression levels of miR-211-5p were down-regulated in the normal cerebral cortexes of mice. However, in APPswe/PS1ΔE9 double transgenic adult mice, it was up-regulated from 9 months of age compared to that of the age-matched wild type mice. Studies in primary cortical neuron cultures demonstrated that miR-211-5p can inhibit neurite growth and branching via NUAK1 repression and decrease mature neuron viability. The impairments were more obvious under the action of Aß. Our data showed that miR-211-5p could inhibit cortical neuron differentiation and survival, which may contribute to the synaptic failure, neuronal loss and cognitive dysfunction in AD.

miR-153-3p, a new bio-target, is involved in the pathogenesis of acute graft-versus-host disease via inhibition of indoleamine- 2,3-dioxygenase.

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Therefore, seeking reliable biomarkers and delineating the potential biological mechanism are important for optimizing treatment strategies and improving their curative effect. In this study, using a microRNA polymerase chain reaction (PCR)-based chip assay, microRNA-153-3p (miR-153-3p) was screened and selected as a potential biomarker of aGVHD. The elevated plasma miR-153-3p levels at +7 d after transplant could be used to predict the upcoming aGVHD. The area under the receiver operating characteristic curve for aGVHD+/aGVHD- patients receiving haploidentical transplant was 0.808 (95% confidence interval, 0.686-0.930) in a training set and 0.809 (95% confidence interval, 0.694-0.923) in a validation set. Interestingly, bioinformatics analysis indicated that indoleamine-2,3-dioxygenase (IDO) is a potential target of miR-153-3p. In vitro study confirmed that IDO could be directly inhibited by miR-153-3p. In a GVHD model, recipient mice injected with a miR-153-3p antagomir exhibited higher IDO expression levels at the early stage after transplantation, as well as delayed aGVHD and longer survival, indicating that the miR-153-3p level at +7 d post-transplant is a good predictor of aGVHD. miR-153-3p participates in aGVHD development by inhibiting IDO expression and might be a novel bio-target for aGVHD intervention.

An Evaluation of the Cobas4800 HPV Test on Cervico-Vaginal Specimens in Liquid versus Solid Transport Media.

OBJECTIVES: Determine the ability of the Cobas 4800 assay to detect high-risk human papillomavirus (HrHPV) and high-grade cervical lesions when using cervico-vaginal samples applied to liquid medium and solid media cards compared to a direct cervical sample. METHODS: Two cervico-vaginal specimens (pseudo self-collected) were obtained from 319 women. One was applied to an iFTA Card (FTA) then the brush placed in liquid-based medium (LSELF); the other was applied to a new solid media: POI card (POI). The clinical performance of Cobas4800 assay using the three aforementioned specimens was compared to direct collected endocervical specimens in liquid media (LDOC). RESULTS: The overall agreements of HrHPV detection were 84.2% (LSELF vs. LDOC), 81.0% (FTA vs. LDOC), and 82.3% (POI vs. LDOC). LSELF, FTA and POI identified 98.0%, 79.6%, and 97.5% positive cases of LDOC. Sensitivity to identify CIN2+ were 98.4% (LSELF), 73.8% (FTA), 95.1% (POI), and 93.4% (LDOC) respectively. FTA had 78.1% and 90.4% agreement with the LSELF samples for all HrHPV and HPV16/18 detection respectively, while POI had 91.6% for both. CONCLUSIONS: Cobas4800 HPV test combined with cervico-vaginal specimens applied to both liquid media and POI solid card are accurate to detect HrHPV infection and high-grade cervical lesions as compared with direct endocervical samples in liquid media.