CellGO: a novel deep learning-based framework and webserver for cell-type-specific gene function interpretation.

Interpreting the function of genes and gene sets identified from omics experiments remains a challenge, as current pathway analysis tools often fail to consider the critical biological context, such as tissue or cell-type specificity. To address this limitation, we introduced CellGO. CellGO tackles this challenge by leveraging the visible neural network (VNN) and single-cell gene expressions to mimic cell-type-specific signaling propagation along the Gene Ontology tree within a cell. This design enables a novel scoring system to calculate the cell-type-specific gene-pathway paired active scores, based on which, CellGO is able to identify cell-type-specific active pathways associated with single genes. In addition, by aggregating the activities of single genes, CellGO extends its capability to identify cell-type-specific active pathways for a given gene set. To enhance biological interpretation, CellGO offers additional features, including the identification of significantly active cell types and driver genes and community analysis of pathways. To validate its performance, CellGO was assessed using a gene set comprising mixed cell-type markers, confirming its ability to discern active pathways across distinct cell types. Subsequent benchmarking analyses demonstrated CellGO's superiority in effectively identifying cell types and their corresponding cell-type-specific pathways affected by gene knockouts, using either single genes or sets of genes differentially expressed between knockout and control samples. Moreover, CellGO demonstrated its ability to infer cell-type-specific pathogenesis for disease risk genes. Accessible as a Python package, CellGO also provides a user-friendly web interface, making it a versatile and accessible tool for researchers in the field.

The mediation roles of self-regulation and problematic internet use: How maladaptive parenting during the COVID-19 pandemic influenced adolescents' academic procrastination in the postpandemic era.

INTRODUCTION: In the transition to the postpandemic era, adolescents are working to shift their focus back to school. However, the prevalence of academic procrastination is reflective of that the aftereffects of the pandemic are persisting. Literature documents the increases in the negative parenting behaviors and internet use of adolescents during the pandemic. The excessive internet use has to do with adolescents' self-regulatory capabilities and self-regulation is profoundly shaped by parents' parenting practices. Given the connections among these factors, the present study seeks to understand how maladaptive parenting practices during the pandemic influenced adolescents' academic procrastination postpandemic through the mediation of self-regulation and problematic internet use. METHOD: Using three waves of data from a total of 1062 Chinese adolescents (Mage = 14.9 years old, SD = 1.6, 13-18 years old; 45% female), we used structural equation modeling to examine the direct effect of maladaptive parenting on academic procrastination and its indirect effect via self-regulation and problematic internet use. RESULTS: Maladaptive parenting during the pandemic did not directly predict adolescent academic procrastination post-pandemic. Yet, maladaptive parenting indirectly influenced academic procrastination both through self-regulation solely and self-regulation and problematic internet use sequentially. CONCLUSION: The findings demonstrate that parents can contribute to adolescents' academic procrastination by influencing their self-regulation ability, which further impacts their internet use. Self-regulation serves as a robust mediator between parenting and adolescents' problematic behaviors related to internet use and learning. Implications for parents and intervention oriented toward adolescents are discussed.

Characterization and genome analysis of two new Aeromonas hydrophila phages, PZL-Ah1and PZL-Ah8.

Aeromonas hydrophila (A. hydrophila) is an opportunistic pathogen of fish, humans, and livestock, and has a severe negative impact on aquaculture development. Phage therapy is considered an alternative strategy for controlling bacterial infections and contamination. In this study, we isolated and characterized the genomes of two A. hydrophila-specific phages, PZL-Ah1 and PZL-Ah8, which, based on transmission electron microscopy, were identified as members of the family Podoviridae. Both of these phages had a relatively narrow host range, with lytic activity against Aeromonas spp. strains. Whole-genome sequence analysis revealed that PZL-Ah1 and PZL-Ah8 have a double-stranded DNA genome of 38,641 bp and 40,855 bp in length, with a GC content of 53.68% and 51.89%, respectively. Forty-four open reading frames (ORFs) were predicted in PZL-Ah1, and 52 were predicted in PZL-Ah8. Twenty-eight (63.6%) ORFs in PZL-Ah1 and 29 (55.8%) ORFs in PZL-Ah8 were predicted to encode functional proteins with homologs in the NCBI database, while the remaining ORFs were classified as encoding hypothetical proteins with unknown functions. A comparison with known phage genes suggested that ORF 02, ORF 29, and ORF 04 of PZL-Ah1 and ORF 2 and ORF 4 of PZL-Ah8 are involved in host cell lysis. This study expands the phage genome database and provides good candidates for phage typing applications.

Use of solution-processed zinc oxide to prevent the breakdown in silver nanowire networks.

The electrical breakdown is a bottleneck preventing AgNW networks from being used in high-current electronics such as transparent heaters or similar applications. The process of failure confirms that Joule-heating plays a key role in the formation of cracks perpendicular to the voltage direction. To improve the transfer of Joule heating, solution-processed ZnO nanoparticles were deposited on a gravure printed AgNW random network with good transparency. The AgNW-ZnO nanocomposites show better heating uniformity at higher temperatures because of their improved thermal conductivity. A 57.7% higher power density was obtained without failure, as well as the improved maximum average temperature rise from 72.2 °C to 97.9 °C, after the AgNW was composited with ZnO. This work opens up a new method to study AgNW failures for applications in high-current electronics.

Trait ontology analysis based on association mapping studies bridges the gap between crop genomics and Phenomics.

BACKGROUND: Trait ontology (TO) analysis is a powerful system for functional annotation and enrichment analysis of genes. However, given the complexity of the molecular mechanisms underlying phenomes, only a few hundred gene-to-TO relationships in plants have been elucidated to date, limiting the pace of research in this "big data" era. RESULTS: Here, we curated all the available trait associated sites (TAS) information from 79 association mapping studies of maize (Zea mays L.) and rice (Oryza sativa L.) lines with diverse genetic backgrounds and built a large-scale TAS-derived TO system for functional annotation of genes in various crops. Our TO system contains information for up to 18,042 genes (6345 in maize at the 25 k level and 11,697 in rice at the 50 k level), including gene-to-TO relationships, which covers over one fifth of the annotated gene sets for maize and rice. A comparison of Gene Ontology (GO) vs. TO analysis demonstrated that the TAS-derived TO system is an efficient alternative tool for gene functional annotation and enrichment analysis. We therefore combined information from the TO, GO, metabolic pathway, and co-expression network databases and constructed the TAS system, which is publicly available at http://tas.hzau.edu.cn . TAS provides a user-friendly interface for functional annotation of genes, enrichment analysis, genome-wide extraction of trait-associated genes, and crosschecking of different functional annotation databases. CONCLUSIONS: TAS bridges the gap between genomic and phenomic information in crops. This easy-to-use tool will be useful for geneticists, biologists, and breeders in the agricultural community, as it facilitates the dissection of molecular mechanisms conferring agronomic traits in an easy, genome-wide manner.

Computer-aided design of microfluidic resistive network using circuit partition and CFD-based optimization and application in microalgae assessment for marine ecological toxicity.

We present an automatic design process for microfluidic dilution network towards marine ecological toxicity assessment on microalgae. Based on the hydraulic-electric circuit analogy, we defined an abstract specification using computer-aided designing system. Several approaches, especially circuit partition, were applied to minimize design effort. Computational fluid dynamics (CFD) simulation was exploited to convert the electrics specification to fabrication model. We automatically designed the combinational-mixing-serial dilution microfluidics to generate parallel stepwise gradients for mixing chemicals (binary/ternary/quaternary mixture) using the present algorithm. We critically discussed design rules and evaluated the microfluidic performance by colorimetric analysis. To examine whether these microfluidic chips can be used for toxicity test on microalgae, single and joint toxic effects of heavy metals (copper, mercury, zinc, and cadmium) were examined on line. In all cases, dose-related toxic responses were successfully detected. These results provided a solution for designing resistive network using circuit partition and CFD-based optimization and a route to develop a promising user-friendly alternative for microalgae bioassays as well as cell-based screening experiments in risk assessment.

Development of Microfluidic Dilution Network-Based System for Lab-on-a-Chip Microalgal Bioassays.

Because of the crucial ecological significance of microalgae, microalgal bioassays have become one of the most demanding tests from all classic aquatic toxicity tests in regulatory frameworks. However, conventional algal tests tend to be lab-intensive and time- and space-consuming, and they have not been utilized to their full potential for routine toxicity assessments. Microfluidics should be a user-friendly alternative. Particularly, dilution to generate gradients that are appropriate for screening experiments can be precisely attained by microfluidic network in a simple and cost-/time-/space-saving way. Here, we demonstrate a microfluidics series toward routine microalgal bioassays, including pretest, single, and joint toxicity test. The chip mainly consists of upstream dilution network (single serial dilution module (logarithmic/linear gradient generator) or multiple (binary/ternary/quaternary) mixing serial dilution module) and downstream diffusible culturing module. It allows the processes of chemical liquid dilution and diffusion, microscale microalgal culture, cell stimulation, and online screening to be integrated into a single device. Electric theorems with the aid of EDA (electronic design automation) simulation were innovatively introduced to minimize design effort for such systems. Using the device, microalgae were successfully cultured and stressed on-chip. The simple assay provides multibiological trait assessments of cell division rate, autofluorescence, esterase activity, and mobile capacity. This work showed promise in developing a high-throughput microfluidic platform for microalgal bioassays as well as lab-on-a-chip screening experiments in the cell-based quantitative assessment of environmental health risks.

An on-chip pollutant toxicity determination based on marine microalgal swimming inhibition.

We report the use of microalgal swimming behavior as a sensor signal integrated into microfluidics for a rapid and high-throughput determination of pollutant toxicity. There are two types of chip. A poly(dimethylsiloxane) (PDMS) 12-well chip, used for optimization of experimental conditions (i.e. light level, temperature, initial cellular density and exposure time), can perform twelve parallel tests simultaneously. In a concentration gradient generator (CGG) chip, a CGG connected with diffusible chambers enables a large number of dose-response bioassays to be performed in a simple way. Microalgal swimming was set as a microfluidic bioassay signal and was evaluated as swimming manner, motile percentage (%MOT), curvilinear velocity (VCL), average path velocity (VAP) and straight line velocity (VSL). Under optimized physical conditions, the toxicities of Cu, Pb, phenol and nonylphenol (NP) towards four mobile marine microalgae, Platymonas subcordiformis, Platymonas helgolandica var. tsingtaoensis, Isochrysis galbana and Isochrysis zhanjiangensis sp. nov, were investigated. In all cases, a toxic response (i.e. a dose-related inhibition of swimming) was detected, and a time of only 2 h was needed to predict EC50 values. The 2h-EC50s showed that I. galbana was the most tolerant and that P. subcordiformis was one of the most sensitive. Based on the relative motile percentage data, the EC50 values for Cu of I. galbana and P. subcordiformis were 6.04 and 1.67 µM, respectively, while for Pb the EC50 values were 15.30 and 3.87 µM, for phenol the EC50 values were 8.69 and 6.08 mM, and for NP the EC50 values were 29.65 and 14.47 µM, respectively. Taking into account all the swimming inhibition parameters, MOT provided more sensitive EC results. The sensitivity differences between the velocity parameters (VCL, VAP and VSL) were ascribed to differences in swimming manner of the different classes of microalgae.

Water-bath assisted convective assembly of aligned silver nanowire films for transparent electrodes.

Manipulating Ag nanowire (AgNW) assembly to tailor the opto-electrical properties and surface morphology could improve the performance of next-generation transparent conductive electrodes. In this paper, we demonstrated a water-bath assisted convective assembly process at the temporary water/alcohol interface for fabricating hierarchical aligned AgNW electrodes. The convection flow plays an important role during the assembly process. The assembled AgNW film fabricated via three times orthogonal dip-coating at a water-bath temperature of 80 °C has a sheet resistance of 11.4 Ω sq(-1) with 89.9% transmittance at 550 nm. Moreover, the root mean square (RMS) of this assembled AgNW film was only 15.6 nm which is much lower than the spin-coated random AgNW film (37.6 nm) with a similar sheet resistance. This facile assembly route provides a new way for manufacturing and tailoring ordered nanowire-based devices.

Paper-based three-dimensional microfluidic device for monitoring of heavy metals with a camera cell phone.

A 3D paper-based microfluidic device has been developed for colorimetric determination of selected heavy metals in water samples by stacking layers of wax patterned paper and double-sided adhesive tape. It has the capability of wicking fluids and distributing microliter volumes of samples from single inlet into affrays of detection zones without external pumps, thus a range of metal assays can be simply and inexpensively performed. We demonstrate a prototype of four sample inlets for up to four heavy metal assays each, with detection limits as follows: Cu (II) = 0.29 ppm, Ni(II) = 0.33 ppm, Cd (II) = 0.19 ppm, and Cr (VI) = 0.35 ppm, which provided quantitative data that were in agreement with values gained from atomic absorption. It has the ability to identify these four metals in mixtures and is immune to interferences from either nontoxic metal ions such as Na(I) and K(I) or components found in reservoir or beach water. With the incorporation of a portable detector, a camera mobile phone, this 3D paper-based microfluidic device should be useful as a simple, rapid, and on-site screening approach of heavy metals in aquatic environments.

An integrated microfludic device for culturing and screening of Giardia lamblia.

In vitro culturing of trophozoites was important for research of Giardia lamblia (G. lamblia), especially in discovery of anti-Giardia agents. The current culture methods mainly suffer from lab-intension or the obstacle in standardizing the gas condition. Thus, it could benefit from a more streamlined and integrated approach. Microfluidics offers a way to accomplish this goal. Here we presented an integrated microfluidic device for culturing and screening of G. lamblia. The device consisted of a polydimethylsiloxane (PDMS) microchip with an aerobic culture system. In the microchip, the functionality of integrated concentration gradient generator (CGG) with micro-scale cell culture enables dose-response experiment to be performed in a simple and reagent-saving way. The diffusion-based culture chambers allowed growing G. lamblia at the in vivo like environment. It notable that the highly air permeable material of parallel chambers maintain uniform anaerobic environment in different chambers easily. Using this device, G. lamblia were successfully cultured and stressed on-chip. In all cases, a dose-related inhibitory response was detected. The application of this device for these purposes represents the first step in developing a completely integrated microfluidic platform for high-throughput screening and might be expanded to other assays based on in vitro culture of G. lamblia with further tests.

[Efficacy of standard antiviral therapy retreatment following interferon treatment failure in chronic hepatitis C patients].

OBJECTIVE: To investigate the therapeutic efficacy of standard antiviral therapy applied after interferon (IFN) treatment failure in patients with chronic hepatitis C (CHC). METHODS: CHC patients who completed a 48-week course of IFN therapy (pegylated (Peg)-IFNa-2a at 180 mug, qw, ih with or without ribavirin (RBV) at 15 mg/kg/w) in our hospital between January 2009 and June 2012 but who showed no response (at week 48) or who relapsed (at week 72) were enrolled in the study. Prior to initiating the 48-week course of retreatment therapy (Peg-IFNa-2a plus RBV as above), the hepatitis C virus (HCV) genotype was detected and the viral load measured (baseline) by PCR of HCV RNA. Each patient's response to therapy was classified as follows: baseline vs. week 4 (rapid virological response, RVR), vs. weeks 12 and 24 (early virological response, EVR), vs. week 48 (end of treatment virological response, ETVR) and vs. week 72 (sustained virological response, SVR). RESULTS: Of the total 235 cases administered retreatment therapy, 60.0% (n = 140) achieved RVR, 77.4% (n = 182) achieved EVR, 83.8% (n = 197) achieved ETVR, 68.0% (n = 68%) achieved SVR, and 15.7% (n = 37) relapsed. Stratification analysis of recurrence (n = 158) and non-responsive (n = 77) sub-groups showed that the recurrence group experienced significantly higher rates of RVR, EVR, ETVR and SVR, but a significantly lower rate of relapse. Stratification analysis of genotype 1b carrier (n = 206) and non-1b carrier (n = 29) sub-groups showed that the 1b carriers had significantly lower rates of RVR, EVR, ETVR and SVR, but a significantly higher rate of relapse. Finally, the patients who achieved RVR (vs. non RVR, n = 95) and EVR (vs. non-EVR, n = 53) showed higher rates of SVR and ETVR. CONCLUSION: CHC patients who fail to respond to the initial course of standard IFN-based therapy may achieve SVR upon retreatment, especially those infected with the HCV genotype 1b.

Genetic mapping and functional analysis of a classical tassel branch number mutant Tp2 in maize.

Tassel branch number is a key trait that contributes greatly to grain yield in maize (Zea mays). We obtained a classical mutant from maize genetics cooperation stock center, Teopod2 (Tp2), which exhibits severely decreased tassel branch. We conducted a comprehensive study, including phenotypic investigation, genetic mapping, transcriptome analysis, overexpression and CRISPR knock-out, and tsCUT&Tag of Tp2 gene for the molecular dissection of Tp2 mutant. Phenotypic investigation showed that it is a pleiotropic dominant mutant, which is mapped to an interval of approximately 139-kb on Chromosome 10 harboring two genes Zm00001d025786 and zma-miR156h. Transcriptome analysis showed that the relative expression level of zma-miR156h was significantly increased in mutants. Meanwhile, overexpression of zma-miR156h and knockout materials of ZmSBP13 exhibited significantly decreased tassel branch number, a similar phenotype with Tp2 mutant, suggesting that zma-miR156h is the causal gene of Tp2 and targets ZmSBP13 gene. Besides, the potential downstream genes of ZmSBP13 were uncovered and showed that it may target multiple proteins to regulate inflorescence structure. Overall, we characterized and cloned Tp2 mutant, and proposed a zma-miR156h-ZmSBP13 model functioning in regulating tassel branch development in maize, which is an essential measure to satisfy the increasing demands of cereals.

Update analysis of studies on the MMP-9 -1562 C>T polymorphism and cancer risk.

Polymorphisms in the matrix metalloproteinase (MMP) gene have been hypothesized to be functional and may contribute to genetic susceptibility to cancers. The common sequence variation in MMP-9 -1562 C>T (rs3918242), has been involved in cancer risk. However, results of the related published studies were somewhat controversial and underpowered in general. To clarify the role of MMP-9 -1562 C>T genotype in global cancer, we performed a meta-analysis of all the available published studies involving 4,124 cancer patients and 4,728 control subjects. The overall results indicated that there was no major association of the variant on cancer risk. However, stratified analysis by cancer type showed that the MMP-9 -1562 C>T polymorphism has a lower risk in colorectal cancer (OR = 0.80, 95%CI = 0.66-0.96, P (heterogeneity) = 0.391) and lung cancer (OR = 0.70, 95%CI = 0.51-0.96, P (heterogeneity) = 0.959) by allelic contrast. Furthermore, association of the MMP-9 -1562 C>T polymorphism and cancer risk was also observed in hospital-based studies under the dominant genetic model (OR = 0.87, 95%CI = 0.78-0.97, P (heterogeneity) = 0.355), allelic contrast (OR = 0.85, 95%CI = 0.75-0.96, P (heterogeneity) = 0.271) and heterozygote comparison (OR = 0.89, 95%CI = 0.79-0.99, P (heterogeneity) = 0.402). This pooled analysis showed evidence that the MMP-9 -1562 C>T polymorphism may decrease both the colorectal and lung cancer risk. Further prospective studies with larger numbers of participants worldwide are required to evaluate the association in more detail.

[Expression of Notch1 in the genital tubercle of male rats with hypospadias induced by Di-n-butyl phthalate].

OBJECTIVE: To detect the differential expression of Notch1 in the genital tubercle (GT) of fetal male rats with hypospadias induced by maternal exposure to Di-n-butyl phthalate (DBP) and that in normal control fetal rats in order to further explore the role of Notch1 in DBP-induced hypospadias. METHODS: Twenty pregnant SD rats were equally and randomly divided into an experimental and a control group, the former given DBP and the latter soybean oil intragastrically at 800 mg/(kg x d) and 2 ml/d respectively from gestation day (GD) 14 to GD 18. On GD 19, the birth weight (BW), anogenital distance (AGD) and hypospadias incidence were recorded, GTs of the fetal male rats collected, and the expression of Notch1 analyzed by Western blot and immunohistochemistry. RESULTS: The BW of the fetal male rats was (4.40 +/- 0.30) g in the experimental group, significantly lower than (6.11 +/- 0.40) g in the control (P <0.05), and the AGD was (2.17 +/- 0.18) mm in the former, markedly shorter than (3.28 +/- 0.16) mm in the latter (P<0.05). The incidence of hypospadias was 42.9%. The relative expression of Notch1 was remarkably lower in the hypospadiac rats than in the normal controls (0.671 +/- 0.021 vs 1.327 +/- 0.031, P<0.05), and it was mainly located in the epithelial cells of the GT. The staining intensity was obviously weaker in the hypospadias than in the normal control group. CONCLUSION: DBP has an obvious toxic effect on fetal male rats and can change the expression of Notch1 in the GT. It possibly affects cell proliferation and apoptosis and epithelial-to-mesenchymal transition (EMT), resulting in the occurrence of hypospadias.

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis.

Liver fibrosis is a common pathologic stage of the development of liver failure. It has showed that exosomes loaded with therapeutic circRNAs can be manufactured in bulk by exosome secreted cells in vitro, thus enabling personalized treatment. This study aimed to investigate the role of exosome-based delivery of circDIDO1 in liver fibrosis. Levels of genes and proteins were examined by qRT-PCR and Western blot. Cell proliferation, apoptosis, and cell cycle were analyzed by using cell counting kit-8 (CCK-8) assay, EdU assay, and flow cytometry, respectively. The binding between circDIDO1 and miR-141-3p was confirmed by dual-luciferase reporter, RNA pull-down and RIP assays. Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. CircDIDO1 overexpression or miR-141-3p inhibition suppressed the proliferation, reduced pro-fibrotic markers, and induced apoptosis as well as cell cycle arrest in hepatic stellate cells (HSCs) by blocking PTEN/AKT pathway. Mechanistically, circDIDO1 acted as an endogenous sponge for miR-141-3p, further rescue experiments showed that circDIDO1 suppressed HSC activation by targeting miR-141-3p. Extracellular circDIDO1 could be incorporated into exosomes isolated from mesenchymal stem cells (MSCs), and transmitted to HSCs to restrain HSC activation. Clinically, low levels of serum circDIDO1 in exosome were correlated with liver failure, and serum exosomal circDIDO1 had a well diagnostic value for liver fibrosis in liver failure patients. Transfer of circDIDO1 mediated by MSC-isolated exosomes suppressed HSC activation through the miR-141-3p/PTEN/AKT pathway, gaining a new insight into the prevention of liver fibrosis in liver failure patients.

Case Report: Chronic hepatitis E in a hematopoietic stem cell transplant recipient: The first report of hepatitis E virus genotype 4 causing chronic infection in a non-solid organ recipient.

Hepatitis E virus (HEV) is one of the most important public health issues around the world, and chronic HEV infection has been reported in immunosuppressed individuals. This study reported a male case, with very severe aplastic anemia (AA), who developed chronic hepatitis E after hematopoietic stem cell transplantation (HSCT). Abnormal alanine aminotransferase (ALT) appeared after HSCT and persisted for twenty-nine months. The case was seropositive for anti-HEV IgG and IgM after HSCT. Twenty-two months after HSCT, HEV RNA and antigen (Ag) testing were positive and persisted for five and seven months, respectively. Positive stains of HEV Ag were present in a liver biopsy sample. HEV Ag was present in bone marrow. The individual rapidly developed liver cirrhosis and was rescued by a regimen of oral ribavirin. These factors suggested there is a risk of HEV infection in HSCT recipients.

RNASEL -1385G/A polymorphism and cancer risk: a meta-analysis based on 21 case-control studies.

Polymorphisms in the endoribonuclease L (RNASEL) gene have been hypothesized to increase the incidence of cancer. The common sequence variation in RNASEL, -1385G/A (rs486907) has been involved in several types of cancer risk. However, results of the related published studies remained conflicting rather than conclusive. To clarify the role of RNASEL -1385G/A genotype in global cancer, we performed a meta-analysis of all the available published studies involving 8,732 cancer patients and 8,748 control subjects. The overall results indicated that there was no major influence of the variant on cancer risk. However, stratified analysis by ethnicity showed that the RNASEL -1385G/A polymorphism has an increased cancer risk in African descendents in the homozygote comparison (OR = 2.59, 95% CI = 1.27-5.27), although no association was found in the analysis stratified by cancer type (OR = 1.12, 95% CI = 0.94-1.35). This meta-analysis suggested that the RNASEL -1385G/A polymorphism is associated with cancer risk in African descendents. To draw more comprehensive conclusions, further prospective studies with larger numbers of participants worldwide are still required to examine associations between RNASEL -1385G/A polymorphism and cancer risk.

[Identification the relationship between mutation patterns of rtM204I/V in the polymerase gene and genotypes of hepatitis B virus].

OBJECTIVE: To investigate the relationship between the mutation patterns of rtM204V/I (methionine to valine or isoleucine at position rt204 of reverse transcriptase domain) in hepatitis B virus (HBV) polymerase gene and HBV genotypes. METHODS: A total of 2849 HBV complete genome sequences were retrieved from the GenBank/EMBL/DDBJ. HBV genotypes were determined by using MEGA4 software. The amino acid sequences of the reverse transcriptase (RT) domain were aligned. Data were analyzed using SPSS 13.0. RESULTS Among the 2849 HBV complete genome sequences, 217 strains with Y (I/V) DD were identified. Of them, 120 had YIDD mutation and the genotype/subgenotype distribution was as follows: A (2), B(B2 19), C(C1 1, C2 78, C5 1), D(17), E(1), G(1); 97 had YVDD mutation and the genotype/subgenotype distribution was as follows: A(17), B(B2 22), C(C1 3, C2 48), D(3), G(3), H(1). There is a significant difference in the mutation patterns of Y (I/V) DD among genotypes of A-D, A-C, and between genotype A and B, P < 0.01.There is a difference in the mutation pattern of Y (I/V) DD among genotypes of B-D, between genotype C and D, P < 0.05. Genotype A has a higher tendency to develop YVDD mutation, whereas genotype D has a higher frequency to develop YIDD mutation. The rtM204V-rtL180M mutations were more frequently found in subgenotype B2 than in subgenotype C2 while the rtM204V-rtL180M-rtV173L mutations were more associated with subgenotype C2 (P < 0.01). CONCLUSION: Different HBV genotype/subgenotype may select different mutation pattern in the YMDD domain. Subgenotype C2 is more diversity and complexity than other HBV genotypes/subgenotypes.

Effects of miR-103a-3p Targeted Regulation of TRIM66 Axis on Docetaxel Resistance and Glycolysis in Prostate Cancer Cells.

Objective: We aimed to study the expressions of miR-103a-3p and TRIM66 in prostate cancer (PCa) cells, explore the direct target genes of miR-103a-3p, and analyze the effects of miR-103a-3p targeted regulation of the TRIM66 axis on docetaxel (DTX) resistance and glycolysis of PCa cells. Methods: Human normal prostate cells and PCa cells were used to detect the expressions of miR-103a-3p and TRIM66 and analyze their relationship. DTX-resistant (DR) PCa cells were established and transfected with miR-103a-3p and TRIM66 plasmids. The MTT assay, the plate cloning assay, the wound healing assay, and the Transwell assay were used to detect cell viability, colony formation, cell migration, and cell invasion, respectively. Cell glycolysis was analyzed using a cell glycolysis kit. Results: The expression of miR-103a-3p was low and that of TRIM66 was high in PCa cells. MiR-103a-3p had a binding site with TRIM66, and the double luciferase report confirmed that they had a targeting relationship. Compared with the PCa group cells, the DTX-resistant group cells showed increased resistance to DTX. The resistance index was 13.33, and the doubling time of the DTX-resistant group cells was significantly longer than that of the PCa group cells. The DTX-resistant group showed more obvious low expression of miR-103a-3p and high expression of TRIM66. After the DTX-resistant group cells were transfected with miR-103a-3p and TRIM66 plasmids, the expression of miR-103a-3p increased significantly and that of TRIM66 decreased significantly. Upregulation of miR-103a-3p and interference with TRIM66 can inhibit the proliferation, metastasis, and glycolysis of DTX-resistant cells. Conclusion: The expression of miR-103a-3p was downregulated and that of TRIM66 was upregulated in the malignant progression of PCa, especially during DTX resistance. Upregulation of miR-103a-3p and interference with TRIM66 can inhibit DTX resistance and glycolysis of PCa cells. Targeting TRIM66 may provide potential application value in molecular therapy for PCa.