Genetic variability of human papillomavirus type 18 based on E6, E7 and L1 genes in central China.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16. METHODS: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively. RESULTS: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes. CONCLUSION: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.

Prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum among outpatients in central China: A retrospective study.

Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU) are the common sexually transmitted pathogens and lead to genital diseases, highly prevalent all around the world. The objective of this study was to analyze the prevalence of NG, CT and UU among outpatients in central China. A total of 2186 urogenital swabs were collected from the patients and the NG, CT and UU pathogens were testing with RT-PCR method, meanwhile the medical records were obtained from the hospital information system. The overall infection rates of NG, CT and UU were 4.57 %, 6.63 % and 48.81 % respectively, showed the prevalence of UU was higher than NG and CT. The younger people had the highest infection rate of NG (10.81 %), CT (20.54 %) and UU (54.59 %). Single infection (89.09 %) was significant higher than co-infection (10.91 %), and the CT-UU co-infection was the prominent pattern (66.41 %). There were an obvious sex difference, the prevalence of NG and CT were significant higher in male, whereas UU was higher in female. Our study could contributed a better understanding of the prevalence of NG, CT and UU, facilitating to the development of effective screening, prevention and treatment policies.

The effect of the initial temperature, pressure, and shape of carbon nanopores on the separation process of SiO2 molecules from water vapor by molecular dynamics simulation.

Today, with the advancement of science in nanotechnology, it is possible to remove dust nanostructures from the air breathed by humans or other fluids. In the present study, the separation of SiO2 molecules from H2O vapor is studied using molecular dynamics (MD) simulation. This research studied the effect of initial temperature, nanopore geometry, and initial pressure on the separation of SiO2 molecules. The obtained results show that by increasing the temperature to 500 K, the maximum velocity (Max-Vel) of the samples reached 2.47 Å/fs. Regarding the increasing velocity of particles, more particles pass via the nanopores. Moreover, the shape of the nanopore could affect the number of passing particles. The results show that in the samples with a cylindrical nanopore, 20 and 40% of SiO2 molecules, and with the sphere cavity, about 32 and 38% of SiO2 particles passed in the simulated structure. So, it can be concluded that the performance of carbon nanosheets with a cylindrical pore and 450 K was more optimal. Also, the results show that an increase in initial pressure leads to a decrease in the passage of SiO2 particles. The results reveal that about 14 and 54% of Silica particles passed via the carbon membrane with increasing pressure. Therefore, for use in industry, in terms of separating dust particles, in addition to applying an EF, temperature, nanopore geometry, and initial pressure should be controlled.

Prevalence and genotype distribution of human papillomavirus infection among women in Jingzhou, China: a population-based study of 51,720 women.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide with a serious threat to women's health. Persistent infection with high-risk human papillomavirus (HR-HPV) has been identified as the main cause of cervical cancer. This study aimed to evaluate the prevalence and genotype distribution of HR-HPV among women in Jingzhou, Hubei province, China, which is critical for the government to formulate the precision strategies of cervical cancer screening and HPV vaccine innoculation. METHODS: To obtain the baseline data on the population-based prevalence and genotype distribution of HR-HPV infection among age groups and different years, a total of 51,720 women from 2018 to 2022 who went to Jingzhou Hospital Affiliated to Yangtze University for physical examination or gynacological treatment and received HR-HPV DNA genotyping were included in this retrospective study. The possible cervicovaginal infection of 15 high-risk HPV genotypes were analyzed by multiplex fluorescent real-time PCR, including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 82. RESULTS: The overall high-risk HPV prevalence among 51,720 women was 18.75% (9,698/51,720), and the HPV-positive rate of physical examination group (PEG) was 13.22% (541/4,091), which was lower than the HPV-positive rate of gynacological checkup group (GCG) 19.23% (9,157/47,629), with statistical difference (χ2 = 89.069, P < 0.01). The five most common prevalent genotypes were HPV52 (6.55%), HPV58 (3.41%), HPV16 (2.58%), HPV68 (1.82%) and HPV51 (1.57%). Single HPV infection was the predominant (14.36%), which compared to double (3.34%) and multiple (1.05%) infections. The HPV-positive rate was the highest in the > 60 age group (31.73%), and the lowest in the 31-40 age group (15.46%). CONCLUSIONS: The prevalence of high-risk HPV infection among women in Jingzhou area was 18.75%. HPV52, HPV58 and HPV16 genotypes were the most common. The higher prevalence was in the > 60 and ≤ 20 age group, which showed a "U" shape curve, suggesting the necessity of screening among older women to decrease the mortality of cervical cancer.

Characteristics of hematological parameters on admission in COVID-19 Omicron variant infected in Chinese population: a large-scale retrospective study.

BACKGROUND: The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country's epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters' predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). METHODS: A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. RESULTS: Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P < 0.01). The ROC curve further demonstrated that lymphocyte (LYM) counts, neutrophil (NEU) counts, monocyte-to-lymphocyte ratios (MLR), platelet-to-lymphocyte ratios (PLR), white blood cell counts (WBC), and mean corpuscular hemoglobin concentration (MCHC) were the top 6 indicators in diagnosing Omicron infection with fever, with area under the curve (AUC) values of 0.738, 0.718, 0.713, 0.702, 0.700, and 0.687, respectively (P < 0.01). Furthermore, the mean platelet volume (MPV) with an AUC of 0.764, red blood cell count (RBC) with 0.753, hematocrit (HCT) with 0.698, MLR with 0.694, mean corpuscular hemoglobin (MCH) with 0.676, and systemic inflammation response indexes (SIRI) with 0.673 were the top 6 indicators for the diagnosis of COVID-19 patients with PI (P < 0.01). CONCLUSIONS: LYM, NEU, MLR, PLR, WBC, and MCHC can serve as potential prescreening indicators for Omicron infection in fever clinics. Additionally, MPV, RBC, HCT, MLR, MCH, and SIRI can predict the presence of PI in COVID-19 patients infected by the Omicron variant.

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. METHODS: In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV-16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. RESULTS: Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). CONCLUSION: HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

Genetic diversity and functional implication of the long control region in human papillomavirus types 52, 58, and 16 from Central China.

OBJECT: High-risk human papillomavirus (HR-HPV) is a main reason for cervical cancer. The long control region (LCR) of the genome plays a variety of roles in the transcription of the virus. METHODS: LCR sequences were amplified by polymerase chain reaction (PCR) and confirmed by DNA sequencing. MEGA 11.0 software and NCBI blast were used to analyze the sequences and construct the Neighbor-Joining tree. In addition, the JASPAR database was used to predict the potential transcription factor binding sites (TFBS). RESULTS: For HPV-52 LCR, 68 single nucleotide polymorphisms (SNPs), 8 deletions, and 1 insertion were found, 17 of which were novel variations. Most of the variants were clustered in B2 sub-lineage (96.22%). For HPV-58 LCR, 25.43% of samples were prototype. 49 SNPs, 2 deletions, and 1 insertion were observed in the remaining samples. A1 sub-lineage was the most frequent (64.16%). For HPV-16 LCR, 75 SNPs and 2 deletions were identified, 13 of which were newly identified. A total of 55.68% of the variants were distributed in A4 sub-lineage. The JASPAR results suggested that multiple variations occurred in TFBSs, which might affect the function of transcription factors. CONCLUSIONS: This study provides experimental data for further studies on the epidemiology and biological function of LCR. Various LCR mutational data may prove useful for exploring the carcinogenic mechanism of HPV.

Association of TLR4 and TLR9 gene polymorphisms with the risk and progression of cervical lesions in HPV-infected women.

Aim: Toll-like receptors involved in tumor-associated inflammatory response, this study aimed to investigate the role of TLR4 and TLR9 gene polymorphisms in the risk and progression of HPV-related cervical lesions. Materials & methods: A total of 220 cervical lesion patients and 227 healthy controls were enrolled. Single-nucleotide polymorphisms were genotyped using PCR-restriction fragment length polymorphism. Results: A significantly decreased risk of cervical lesions was observed to be associated with the TLR4 rs10116253 (C), rs1927911 (T) and rs10759931 (G) mutant alleles. rs187084-rs1927911-HPV-16/18 was the best interaction model to affect cervical lesion risk. Conclusion: TLR4 rs10116253, rs1927911 and rs10759931 were potential biomarkers for cervical lesion susceptibility.

Cervical lesions are common diseases in women worldwide. Infection with high-risk HPV over a long time is a major risk factor for cervical lesions. Toll-like receptors play an important role in the natural defenses against virus infection. However, they may promote inflammation related to cancer development. The aim of this research was to investigate the association between TLR4/TLR9 gene polymorphisms and the risk/progression of HPV-related cervical lesions. The study found that mutant allele carriers of TLR4 rs10116253 (CT and CT + CC), rs1927911 (CT and CT + TT) and rs10759931 (AG and AG + GG) had a significantly decreased risk of cervical lesions compared with those carrying the wild-type homozygous genotypes. The interaction between TLR4/TLR9 gene polymorphisms and HPV-16/18 infection influenced cervical lesion risk. These results can be used to evaluate the risk of cervical lesions in women with high-risk HPV infection.

Association of TLR4 and TLR9 gene polymorphisms with cervical HR-HPV infection status in Chinese Han population.

BACKGROUND: Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. METHODS: A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case-control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR-RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan-Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. RESULTS: The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan-Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). CONCLUSION: Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.

Metabolic Characteristics of Gestational Diabetes Mellitus and the Effects on Pregnancy Outcomes.

Objective: To describe the metabolic characteristics of gestational diabetes mellitus (GDM) and assess their effects on perinatal outcomes. Methods: A two-center nested case‒control study was designed, including 192 pregnant women with GDM and 191 pregnant women with normal glucose tolerance (NGT). Serum glucose and insulin concentrations based upon the 75 g oral glucose tolerance test (OGTT) were measured. Several indices were calculated to describe the metabolic characteristics of the subjects. The relationship between glucose metabolism parameters and pregnancy outcomes was evaluated using stepwise linear regression and binary logistic regression. Results: Compared with the NGT group, the GDM group showed significantly higher fasting and postprandial glucose parameters but significantly lower fasting and postprandial insulin responses. Meanwhile, the GDM group had significantly lower HOMA-ß, DI and ISIMatsuda but comparable HOMA-IR. The IFG subgroup showed significantly lower FINS/FPG only, while the IGT and IFSG subgroups showed deficiency in both fasting and postprandial insulin response. The IFSG subgroup had the highest glucose parameters and the lowest insulin parameters, as well as significantly lower ISIMatsuda and HOMA-ß than the NGT group. FPG had a significant effect on infants' birth weight, and 1hPG and FINS/FPG had a significant effect on delivery gestational age. AUC-INS, IGI60 and DI were related to premature delivery risk after adjusting for confounders. The IFG subgroup of GDM was 2.319 times more likely to be subject to cesarean section than the NGT group. FPG, FINS/FPG, AUC-GLU, AUC-INS/AUC-GLU and HOMA-ß were related to macrosomia risk. Conclusion: Beta cell dysfunction rather than insulin resistance determines the occurrence of GDM in the central Chinese population. Women with predominant insulin secretion defects had a similar risk of adverse perinatal outcomes to women with NGT. Our study provided a basis for the selection of glucose metabolism monitoring indicators useful for the prevention of adverse perinatal outcomes.

Circadian rhythm sleep disorders and time-of-day-dependent memory deficiency in Presenilin1/2 conditional knockout mice with long noncoding RNA expression profiling changes.

Alzheimer's disease (AD) patients exhibit sleep and circadian disturbances prior to the onset of cognitive decline, and these disruptions worsen with disease severity. However, the molecular mechanisms behind sleep and circadian disruptions in AD patients are poorly understood. In this study, we investigated sleep pattern and circadian rhythms in Presenilin-1/2 conditional knockout (DKO) mice. Assessment of EEG and EMG recordings showed that DKO mice displayed increased NREM sleep time but not REM sleep during the dark phase compared to WT mice at the age of two months; at the age of six months, the DKO mice showed increased wakefulness periods and decreased total time spent in both NREM and REM sleep. WT exhibited time-of-day dependent modulation of contextual and cued memory. Compared with WT mice, 4-month-old DKO mice exhibited the deficiency regardless trained and tested in the same light/night phase or not. Particularly interesting was that DKO showed circadian modulation deficiency when trained in the resting period but not in the active period. Long noncoding RNAs (lncRNAs) are typically defined as transcripts longer than 200 nucleotides, and they have rhythmic expression in mammals. To date no study has investigated rhythmic lncRNA expression in Alzheimer's disease. We applied RNA-seq technology to profile hippocampus expression of lncRNAs in DKO mice during the light (/resting) and dark (/active) phases and performed gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the cis lncRNA targets. Expression alteration of lncRNAs associated with immune response and metallodipeptidase activity may contribute to the circadian disruptions of DKO mice. Especially we identified some LncRNAs which expression change oppositely between day and light in DKO mice compared to WT mice and are worthy to be studied further. Our results exhibited the circadian rhythm sleep disorders and a noteworthy time-of-day-dependent memory deficiency in AD model mice and provide a useful resource for studying the expression and function of lncRNAs during circadian disruptions in Alzheimer's disease.

Genetic variants of the GLP-1R gene affect the susceptibility and glucose metabolism of gestational diabetes mellitus: a two-center nested case‒control study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common complication during pregnancy, occurring under the combined action of environmental and genetic factors. Genetic variants of glucagon-like peptide-1 receptor (GLP-1R) have been reported to affect insulin secretion and susceptibility to type 2 diabetes. This study aimed to explore the role of GLP-1R polymorphisms in GDM and glucose metabolism. METHODS: A two-center nested case‒control study was designed, including 200 pregnant women with GDM and 200 pregnant women without GDM genotyped for five tag SNPs of GLP-1R using Sanger sequencing. Logistic regression was used to evaluate the relationship between GLP-1R polymorphisms and GDM risk. Glucose and insulin concentrations were measured based upon the 75 g oral glucose tolerance test (OGTT). Beta cell function of different genotypes was estimated with the 60 min insulinogenic index (IGI60) and OGTT-derived disposition index (DI). RESULTS: Mutant genotype AG + GG of tag SNP rs6458093 nominally increased GDM risk (p = 0.049), especially among subjects younger than 35 years (p = 0.024) and with BMI no less than 24 (p = 0.041), after adjusting for confounders. Meanwhile, compared with subjects with wild genotype AA, subjects with genotype AG + GG of rs6458093 also showed nominally significantly lower IGI60 (p = 0.032) and DI (p = 0.029), as well as significantly higher 75 g OGTT-based 1 h glucose load plasma glucose levels (p = 0.045). Moreover, the mutant heterozygous genotype GA of tag SNP rs3765467 nominally decreased GDM risk among subjects older than 35 years (p = 0.037) but showed no association with insulin secretion and glucose homeostasis. CONCLUSIONS: Tag SNP rs6458093 of GLP-1R was nominally associated with increased GDM risk and affected beta cell function and postprandial glucose metabolism, while tag SNP rs3765467 of GLP-1R was nominally associated with decreased GDM risk, providing evidence for molecular markers and etiological study of GDM.

Social deficits via dysregulated Rac1-dependent excitability control of prefrontal cortical neurons and increased GABA/glutamate ratios.

Identifying symptom-specific convergent mechanisms for neurodevelopmental disorders is a promising strategy in advancing therapies. Here, we show that bidirectional dysregulation of Rac1 activity in the medial prefrontal cortex (mPFC) dictates shared social deficits in mice. Selective upregulation or downregulation of Rac1 activity in glutamatergic or fast-spiking GABAergic neurons results in excessive or inadequate control of excitability combined with a decrease in glutamate or an increase in GABA concentrations and an increase in the GABA/glutamate ratio, which is responsible for social deficits. Notably, the autism model of Shank3B knockout mice exhibits aberrantly enhanced Rac1 activity, reduced glutamate concentrations, and pyramidal neuron excitability in mPFC accompanied with social deficits, which were corrected by either excitatory-neuron-specific downregulation of Rac1 activity or upregulation of neuronal excitability. Thus, this work shows a convergence between genetic autism risk factors, dysregulation of Rac1 signaling, and excitation-inhibition imbalance, enabling mechanism-based stratification of patients with social deficits.

Genetic variability of E6 and E7 genes of human papillomavirus type 58 in Jingzhou, Hubei Province of central China.

BACKGROUND: Cervical cancer is a common malignant tumor in women, with a high mortality rate, has great harm to women's health. Long-term and persistent infection of high-risk human papillomavirus (HR-HPV) is the main reason of the occurrence and development of cervical cancer. METHODS: The infection rate of HPV-58 is higher in the Jingzhou area. In this study, 172 complete HPV-58 E6-E7 sequences were amplified by polymerase chain reaction (PCR), the amplified products were sequenced, and the gene variations of HPV-58 E6-E7 were analyzed. A Neighbor-Joining phylogenetic tree was constructed by MEGA 11. The secondary structure of E6 and E7 protein was investigated. PAML X was used to analyze the selective pressure. The B cell epitopes of E6 and E7 proteins in HPV-58 were predicted by ABCpred server. RESULTS: In E6 sequences, 10 single nucleotide variants were observed, including 7 synonymous and 3 non-synonymous variants. In E7 sequences, 12 single nucleotide variants were found, including 3 synonymous variants and 9 non-synonymous variants. There are 5 novel variants. The phylogenetic analysis showed that all the E6-E7 sequences were distributed in A lineage. No positively selected site was found in E6 sequence, but G63 in E7 sequences was identified as positively selected site. Some amino acid substitutions affected multiple B cell epitopes. CONCLUSION: Various E6 and E7 mutational data may prove useful for development of better diagnostic and vaccines for the region of Jingzhou, Hubei province of central China.

Genetic variation of E6, E7, and L1 genes of human papillomavirus 51 from central China.

The incidence of cervical cancer is closely related to high-risk human papillomavirus (HR-HPV). Women in Jingzhou had relatively high susceptibility to HPV-51, whose ratio was 9.61% (456/4743) among HR-HPV-positive samples and ranked fifth in all analyzed HR-HPV types. In this study, variations and phylogenetic trees of HPV-51 E6-E7 and L1 sequences were analyzed by MEGA-X. The selective pressure was estimated using PAML. The B-cell epitope of L1 amino acid sequences and T-cell epitope of E6 and E7 amino acid sequences were further predicted by ABCpred server and IEDB website, respectively. In the E6-E7 sequences 14 single nucleotide variants occurred, among which 4 were nonsynonymous variants and 10 were synonymous variants. A total of 41 single nucleotide variants were identified in the L1 sequences, including 10 nonsynonymous variants and 31 synonymous variants. All the isolates of both E6-E7 and L1 were classified into the A variant lineage. In HPV-51 E6-E7 and L1 sequences, no positively selected site was found. Two nonconservative substitutions, H119Y and N176S in L1, affected multiple hypothetical B-cell epitopes. Three nonconservative substitutions, T86P, S100L in E6, and F29L in E7, affected multiple hypothetical T-cell epitopes. Elucidation of the HR-HPV prevalence characteristics and genetic variations of HPV-51 in central China may contribute to future investigations of diagnostic probes, therapeutic or preventative vaccines with wider coverage.

Noncognitive species-typical and home-cage behavioral alterations in conditional presenilin 1/presenilin 2 double knockout mice.

Impairments in activities of daily living (ADL) are common clinical symptoms of human Alzheimer's disease (AD). Describing the ADL in AD animal models might provide more insights into the mechanism/treatment of the disease. Here, we demonstrated that the forebrain presenilin 1(Psen1)/presenilin 2 (Psen2) conditional double knockout (DKO) mice exhibited deficits in nest building, marble burying and food burrowing starting at 3 months old and worsening at later ages. At 4 months of age, spontaneous activities in the home cage were also impaired in DKO mice, including physically demanding activities, habituation-like behaviors, and nourishment behaviors during the first two hours in the dark phase. These results indicated that loss of function of Psen1 and Psen2 in mice impaired a series of noncognitive behaviors in the early phase of neurodegeneration. This observation suggests that DKO mice are an ideal model for further mechanistic studies of Psen1 and Psen2 functions in regulating noncognitive behaviors.

autopsych: An R Shiny tool for the reproducible Rasch analysis, differential item functioning, equating, and examination of group effects.

In this paper, we present autopsych, a novel online tool that allows school assessment experts, test developers, and researchers to perform routine psychometric analyses and equating of student test data and to examine the effect of student demographic and group conditions on student test performance. The app extends current open-source software by providing (1) extensive embedded result narration and summaries for written reports, (2) improved handling of partial credit data via customizable item-person Wright maps, (3) customizable item- and person-flagging systems, (4) item-response theory model constraints and controls, (5) many-facets Rasch analysis to examine item bias, (6) Rasch fixed item equating for mapping student ability across test forms, (7) tabbed spreadsheet outputs and immediate options for secondary data analysis, (8) customizable graphical color schemes, (9) extended ANOVA analysis for examining group differences, and (10) inter-rater reliability analyses for the verifying the consistency of rater scoring systems. We present the app's architecture and functionalities and test its performance with simulated and real-world small-, medium-, and large-scale assessment data. Implications and planned future developments are also discussed.

Chinese Pre-service Music Teachers' Perceptions of Augmented Reality-Assisted Musical Instrument Learning.

Given the rapid growth of music technology, this study reports Chinese pre-service music teachers' perceptions of musical instrument learning assisted by augmented reality (AR). In this study, we conducted a small-scale case study with six pre-service teachers enrolled in a music teacher training programme at a comprehensive university in China. Participants engaged in semi-structured, face-to-face interviews after hands-on experiences with an AR-based piano learning app. Thematic analysis revealed that the participants were generally aware of the potential of this instructional approach but doubted its efficacy and exhibited weak intention to adopt it in their future classrooms. Implications of the findings for music teacher training are discussed.

USF3 modulates osteoporosis risk by targeting WNT16, RANKL, RUNX2, and two GWAS lead SNPs rs2908007 and rs4531631.

Osteoporotic fractures cause major morbidity and mortality in the aging population. Genome-wide association studies (GWAS) have identified USF3 as the novel susceptibility gene of osteoporosis. However, the functional role in bone metabolism and the target gene of the basic helix-loop-helix transcription factor USF3 are unclear. Here, we show that USF3 enhances osteoblast differentiation and suppresses osteoclastogenesis in cultured human osteoblast-like U-2OS cells. Mechanistic studies revealed that transcription factor USF3 antagonistically interacts with anti-osteogenic TWIST1/TCF12 heterodimer in the WNT16 and RUNX2 promoter, and counteracts CREB1 and JUN/FOS in the RANKL promoter. Importantly, the osteoporosis GWAS variant g.1744A>G (rs2908007A>G) located in the WNT16 promoter confers G-allele-specific transcriptional modulation by USF3, TWIST1/TCF12 and TBX5/TBX15, and USF3 transactivates the osteoclastogenesis suppressor WNT16 promoter activity and antagonizes the repression of WNT16 by TWIST1 and TCF12. The risk G allele of osteoporosis GWAS variant g.3260A>G (rs4531631A>G) in the RANKL promoter facilitates the binding of CREB1 and JUN/FOS and enhances transactivation of the osteoclastogenesis contributor RANKL that is inhibited by USF3. Our findings uncovered the functional mechanisms of osteoporosis novel GWAS-associated gene USF3 and lead single nucleotide polymorphisms rs2908007 and rs4531631 in the regulation of bone formation and resorption.

Reconsolidation of a post-ingestive nutrient memory requires mTOR in the central amygdala.

The central control of feeding behavior and metabolic homeostasis has been proposed to involve a form of post-ingestive nutrient learning independent of the gustatory value of food. However, after such learning, it is unknown which brain regions or circuits are activated to retrieve the stored memory and whether this memory undergoes reconsolidation that depends on protein synthesis after its reactivation through retrieval. In the present study, using a conditioned-flavor-preference paradigm by associating flavors with intra-gastric infusion of glucose to minimize the evaluation of the taste of food, we show that retrieval of the post-ingestive nutrient-conditioned flavor memory stimulates multiple brain regions in mice, including the central nucleus of the amygdala (CeA). Moreover, memory retrieval activated the mammalian target of rapamycin complex 1 (mTORC1) in the CeA, while site-specific or systemic inhibition of mTORC1 immediately after retrieval prevented the subsequent expression of the post-ingestive nutrient-associated flavor memory, leading to a long-lasting suppression of reinstatement. Taken together, our findings suggest that the reconsolidation process of a post-ingestive nutrient memory modulates food preferences.