Modeled estimates of HIV-serodifferent couples in tuberculosis-affected households in four sub-Saharan African countries.

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions.

PCSK9 Promotes Hypoxia-Induced EC Pyroptosis by Regulating Smac Mitochondrion-Cytoplasm Translocation in Critical Limb Ischemia.

Hypoxia-induced endothelial cell death and impaired angiogenesis are the main pathophysiological features of critical limb ischemia. Mechanistically, proprotein convertase subtilisin/kexin type 9 (PCSK9) promoted Smac translocation from mitochondria to the cytoplasm. Inhibition of Smac release into the cytoplasm attenuated PCSK9-mediated hypoxia-induced pyroptosis. Functionally, PCSK9 overexpression impaired angiogenesis in vitro and reduced blood perfusion in mice with lower limb ischemia, but the effect was reversed by PCSK9 inhibition. This study demonstrates that PCSK9 aggravates pyroptosis by regulating Smac mitochondrion-cytoplasm translocation in the vascular endothelium, providing novel insights into PCSK9 as a potential therapeutic target in critical limb ischemia.

Identification and Characterization of a Novel Hypovirus from the Phytopathogenic Fungus Botryosphaeria dothidea.

Many mycoviruses have been accurately and successfully identified in plant pathogenic fungus Botryosphaeria dothidea. This study discovered three mycoviruses from a B. dothidea strain SXD111 using high-throughput sequencing technology. A novel hypovirus was tentatively named Botryosphaeria dothidea hypovirus 1 (BdHV1/SXD111). The other two were known viruses, which we named Botryosphaeria dothidea polymycovirus 1 strain SXD111 (BdPmV1/SXD111) and Botryosphaeria dothidea partitivirus 1 strain SXD111 (BdPV1/SXD111). The genome of BdHV1/SXD111 is 11,128 nucleotides long, excluding the poly (A) tail. A papain-like cysteine protease (Pro), a UDP-glucose/sterol glucosyltransferase (UGT), an RNA-dependent RNA polyprotein (RdRp), and a helicase (Hel) were detected in the polyprotein of BdHV1/SXD111. Phylogenetic analysis showed that BdHV1/SXD111 was clustered with betahypovirus and separated from members of the other genera in the family Hypoviridae. The BdPmV1/SXD111 genome comprised five dsRNA segments with 2396, 2232, 1967, 1131, and 1060 bp lengths. Additionally, BdPV1/SXD111 harbored three dsRNA segments with 1823, 1623, and 557 bp lengths. Furthermore, the smallest dsRNA was a novel satellite component of BdPV1/SXD111. BdHV1/SXD111 could be transmitted through conidia and hyphae contact, whereas it likely has no apparent impact on the morphologies and virulence of the host fungus. Thus, this study is the first report of a betahypovirus isolated from the fungus B. dothidea. Importantly, our results significantly enhance the diversity of the B. dothidea viruses.

Global-, Regional-, and National-Level Impacts of the COVID-19 Pandemic on Tuberculosis Diagnoses, 2020-2021.

Evaluating cross-country variability on the impact of the COVID-19 pandemic on tuberculosis (TB) may provide urgent inputs to control programs as countries recover from the pandemic. We compared expected TB notifications, modeled using trends in annual TB notifications from 2013-2019, with observed TB notifications to compute the observed to expected (OE) ratios for 170 countries. We applied the least absolute shrinkage and selection operator (LASSO) method to identify the covariates, out of 27 pandemic- and tuberculosis-relevant variables, that had the strongest explanatory power for log OE ratios. The COVID-19 pandemic was associated with a 1.55 million (95% CI: 1.26-1.85, 21.0% [17.5-24.6%]) decrease in TB diagnoses in 2020 and a 1.28 million (0.90-1.76, 16.6% [12.1-21.2%]) decrease in 2021 at a global level. India, Indonesia, the Philippines, and China contributed the most to the global declines for both years, while sub-Saharan Africa achieved pre-pandemic levels by 2021 (OE ratio = 1.02 [0.99-1.05]). Age-stratified analyses revealed that the ≥ 65-year-old age group experienced greater relative declines in TB diagnoses compared with the under 65-year-old age group in 2020 (RR = 0.88 [0.81-0.96]) and 2021 (RR = 0.88 [0.79-0.98]) globally. Covariates found to be associated with all-age OE ratios in 2020 were age-standardized smoking prevalence in 2019 (ß = 0.973 [0.957-990]), school closures (ß = 0.988 [0.977-0.998]), stay-at-home orders (ß = 0.993 [0.985-1.00]), SARS-CoV-2 infection rate (ß = 0.991 [0.987-0.996]), and proportion of population ≥65 years (ß = 0.971 [0.944-0.999]). Further research is needed to clarify the extent to which the observed declines in TB diagnoses were attributable to disruptions in health services, decreases in TB transmission, and COVID-19 mortality among TB patients.

Frequency of HIV serodifferent couples within TB-affected households in a setting with a high burden of HIV-associated TB.

INTRODUCTION: Strong epidemiological links between human immunodeficiency virus (HIV) and tuberculosis (TB) may make household TB contact investigation an efficient strategy for HIV screening and finding individuals in serodifferent partnerships at risk of HIV and linking them to HIV prevention services. We aimed to compare the proportions of HIV serodifferent couples in TB-affected households and in the general population of Kampala, Uganda. METHODS: We included data from a cross-sectional trial of HIV counselling and testing (HCT) in the context of home-based TB evaluation in Kampala, Uganda in 2016-2017. After obtaining consent, community health workers visited the homes of participants with TB to screen contacts for TB and offer HCT to household members ≥ 15 years. We defined index participants and their spouses or parents as couples. Couples were classified as serodifferent if confirmed by self-reported HIV status or by HIV testing results. We used a two-sample test of proportions to compare the frequency of HIV serodifference among couples in the study to its prevalence among couples in Kampala in the 2011 Uganda AIDS Indicator Survey (UAIS). RESULTS: We included 323 index TB participants and 507 household contacts aged ≥ 18 years. Most index participants (55%) were male, while most (68%) adult contacts were female. There was ≥ 1 couple in 115/323 (35.6%) households, with most couples (98/115, 85.2%) including the index participant and spouse. The proportion of households with HIV-serodifferent couples was 18/323 (5.6%), giving a number-needed-to-screen of 18 households. The proportion of HIV serodifference among couples identified in the trial was significantly higher than among couples in the UAIS (15.7% vs. 8%, p = 0.039). The 18 serodifferent couples included 14 (77.8%) where the index participant was living with HIV and the spouse was HIV-negative, and 4 (22.2%) where the index partner was HIV-negative, while the spouse was living with HIV. CONCLUSIONS: The frequency of HIV serodifference among couples identified in TB-affected households was higher than in the general population. TB household contact investigation may be an efficient strategy for identifying people with substantial exposure to HIV and linking them to HIV prevention services.

Molecular characterization of a novel victorivirus isolated from Botryosphaeria dothidea, the causal agent of longan leaf spot disease.

Mycoviruses are widespread in all major taxonomic groups of filamentous fungi. Previous research has indicated that mycoviruses are associated with the phytopathogenic fungus Botryosphaeria dothidea. In this study, three distinct double-stranded RNA viruses were detected in B. dothidea strain YCLYY11 isolated from a leaf spot of longan (Dimocarpus longana). The results of BLAST analysis revealed that the predicted amino acid sequences of those viruses were similar to those of Botryosphaeria dothidea chrysovirus 1, Botryosphaeria dothidea partitivirus 1, and an apparent novel victorivirus. Sequencing and analysis of the complete genome of the novel victorivirus indicated it is 5218 bp in length and contains two open reading frames (ORFs) that overlap at the tetranucleotide AUGA. BLASTp analysis of the proteins encoded by ORF1 and ORF2 showed that they were most similar to the coat protein and RNA-dependent RNA polymerase of Sphaeropsis sapinea RNA virus 2 (81.37% and 74.09% identical, respectively). A phylogenetic tree showed that the novel virus clustered together with victoriviruses and was separate from members of the other four genera of the family Totiviridae. Based on its genome structure and the results of phylogenetic analysis, we propose that this novel victorivirus should be named "Botryosphaeria dothidea victorivirus 3". This is also the first report of these three mycoviruses coinfecting a strain of B. dothidea.

[The incidence of myopia and myopic progression from 2019 to 2020 in school-age children in Zhuozhou].

Objective: To analyze the changes in refractive status and prevalence of myopia in 6-to 14-year-old children at 2 time points in Zhuozhou, Hebei Province. Methods: In the current cohort study, the visual acuity and refractive status of primary and secondary school students aged 6 to 14 years were examined from June to August 2019 and reexamined from June to August 2020. A total of 30 412 subjects with examination data were enrolled, including 15 861 males (52.2%) and 14 551 females (47.8%), with an average age of (10.0±2.7) years. The participants underwent autorefraction without cycloplegia and a naked eye visual acuity test with a standard logarithmic visual acuity chart. Myopia was screened by the standard of equivalent spherical refraction less than -0.75 diopter (D). The categorical data were analyzed by the Chi-square or Fisher's exact test. Clopper-Pearson was used to estimate the 95% confidence intervals for the incidence of myopia. Results: After the 1-year interval, the change of equivalent spherical refraction was(-0.67±1.11) D and(-0.76±1.11) D, respectively, in male and female participants, and their visual acuity decreased by 0.11±0.19 and 0.12±0.21, respectively. There were significant inter-group differences in the annual change of spherical power in different age groups (χ²=276.23, P<0.001). The naked eye visual acuity reduction was greatest in the 10-year-old students. The incidence of myopia was 42.2% (95% confidence intervals of 41.47% to 42.93%) during the 1-year follow-up period. The incidence of myopia was highest at the age of 14 (52.0% in males and 54.2% in females) and lowest at the age of 6 (31.0% in males and 33.1% in females). Conclusions: The 1-year follow-up revealed an obvious myopic shift in the refractive status of school students in Zhuozhou, with their naked eye visual acuity decreased. The incidence of myopia was higher in females than that in males.

A novel posttranslational modification of histone, H3 S-sulfhydration, is down-regulated in asthenozoospermic sperm.

Oxidative stress is one of the major causes leading to male infertility including asthenozoospermia. Hydrogen sulfide (H2S) has been widely recognized to be a potent antioxidant whose role is partially implemented by protein S-sulfhydration. However, protein S-sulfhydration has not been reported in germ cells. Therefore, we investigated whether asthenozoospermia could be associated with sperm protein S-sulfhydration. S-sulfhydrated proteins in human sperm were enriched via biotin-switch assay and analyzed using LC-MS/MS spectrometry. Two hundred forty-four S-sulfhydrated proteins were identified. Importantly, we validated that sperm histones H3.1 and H3.3 were the S-sulfhydrated proteins. Their S-sulfhydrated amino acid residue was Cysteine111. Abundances of S-sulfhydrated H3 (sH3) and S-sulfhydrated H3.3 (sH3.3) were significantly down-regulated in asthenozoospermic sperm, compared with the fertile controls, and were significantly correlated with progressive motility. Retinoic acid (RA) up-regulated level of sH3.3 in primary round spermatids and the C18-4 cells (a mouse spermatogonial stem cell line). Overexpression of the mutant H3.3 (Cysteine111 was replaced with serine) affected expression of 759 genes and raised growth rate of C18-4 cells. For the first time, S-sulfhydration H3 and H3.3 were demonstrated in the present study. Our results highlight that aberrant S-sulfhydration of H3 is a new pathophysiological basis in male infertility.

The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA-RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis.

LncRNAs play essential roles in tumorigenesis and tumor progression. Pseudogene UBE2CP3 is an antisense intronic lncRNA. However, the biological function of UBE2CP3 in gastric cancer (GC) remains unknown. In this study, we revealed that lncRNA UBE2CP3 was aberrantly upregulated in multiple independent gastric cancer cohorts, and its overexpression was clinically associated with poor prognosis in GC. UBE2CP3 was mainly located in cytoplasm and promoted migratory and invasive capacities of GC cells in vitro and in vivo. Mechanismly, a novel dysregulated ceRNA network UB2CP3/miR-138-5p/ITGA2 was identified in GC by transcriptome sequencing. Furthermore, rescue assay further confirmed that UBE2CP3 mainly promoted GC progression through miR-138-5p/ITGA2 axis. More importantly, our data proved that UBE2CP3/IGFBP7 could form an RNA duplex, thereby directly interacting with the ILF3 protein. In turn, this RNA-RNA interaction between IGFBP7 mRNA and UBE2CP3 mediated by ILF3 protein plays an essential role in protecting the mRNA stability of UBE2CP3. In addition, transcription factor ELF3 was identified to be a direct repressor of lncRNA UBE2CP3 in GC. Taken together, overexpression of UBE2CP3 promotes tumor progression via cascade amplification of ITGA2 upregulation in GC. Our finding has revealed that the dysregulation of UBE2CP3 is probably due to the downregulation of ELF3 and/or the overexpression of IGFBP7 mRNA in GC. Our findings reveal, for the first time, that UBE2CP3 plays crucial a role in GC progression by modulating miR-138-5p/ITGA2 axis, suggesting that UBE2CP3 may serve as a potential therapeutic target in GC.

miRNA-194 predicts favorable prognosis in gastric cancer and inhibits gastric cancer cell growth by targeting CCND1.

MicroRNAs (MiRNAs) play critical roles in regulating target gene expression and multiple cellular processes in human cancer malignant progression. However, the function of miR-194 in gastric cancer (GC) remains unclear and controversial. In this study, we identified a series of miRNAs that can serve as prognostic biomarkers for GC by analysis of miRNA expression using The Cancer Genome Atlas data. Among them, miR-100, miR-125b, miR-199a, and miR-194 were the four most promising prognostic biomarkers in GC due to their significant associations with various clinical characteristics of patients. miR-100, miR-125b, and miR-199a predicted poor prognosis in GC, while miR-194 predicted favorable prognosis in GC. We also provide the first comprehensive transcriptome analysis of miR-194 in GC. Our data suggest that miR-194 tends to regulate target genes by binding to their 3' UTRs in a 7-mer-A1, 7-mer-m8, or 8-mer manner. KEGG pathway analysis showed that the cell cycle was one of the pathways most affected by miR-194 in GC. Moreover, CCND1 was shown to be a novel target gene of miR-194 in GC. Additionally, downregulation of CCND1 by miR-194 in GC further led to cell growth inhibition and cell cycle arrest. In conclusion, miR-100, miR-125b, miR-199a, and miR-194 may have potential as prognostic and diagnostic biomarkers for GC. miR-194 suppresses GC cell growth mainly through targeting CCND1 and induction of cell cycle arrest.

Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model.

Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC50 = 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide 64Cu. 64Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14-16 GBq/µmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. 64Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by humanlungadenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after 64Cu-NOTA-Nb6 administration. The study revealed that 64Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, 64Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging.

LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141/200a.

Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor progression. However, the biological function of most lncRNAs remains unknown in human gastric cancer. This study here aims to explore the unknown function of lncRNA MAGI2-AS3 in gastric cancer. First, bioinformatics analysis showed that lncRNA MAGI2-AS3 was overexpressed in gastric cancer tissues, and the overexpression of MAGI2-AS3 has been shown to be associated with poor prognosis in all three independent gastric cancer cohorts (The Cancer Genome Atlas stomach cancer [TCGA_STAD], GEO: GSE62254 and GSE15459). The multivariate analysis indicated that lncRNA MAGI2-AS3 was an independent prognostic factor for both overall survival and disease-free survival of gastric cancer patients. Moreover, MAGI2-AS3 was identified to be an epithelial-mesenchymal transition (EMT)-related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in gastric cancer. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in the cytoplasm of gastric cancer cells. Bioinformatics analysis and functional experiments revealed that lncRNA MAGI2-AS3 was negatively correlated with miR-141/200a expression and negatively regulated miR-141/200a-3p expression in gastric cancer. Therefore, we speculate that lncRNA MAGI2-AS3 promotes tumor progression through sponging miR-141/200a and maintaining overexpression of ZEB1 in gastric cancer. Nevertheless, we identified that BRD4 is a transcriptional regulator of lncRNA MAGI2-AS3 in gastric cancer. Additionally, our findings highlight that lncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for gastric cancer.

Characterization of a Botybirnavirus Conferring Hypovirulence in the Phytopathogenic Fungus Botryosphaeria dothidea.

A double-stranded RNA (dsRNA) virus was isolated and characterized from strain EW220 of the phytopathogenic fungus Botryosphaeria dothidea. The full-length cDNAs of the dsRNAs were 6434 bp and 5986 bp in size, respectively. The largest dsRNA encodes a cap-pol fusion protein that contains a coat protein gene and an RNA-dependent RNA polymerase (RdRp) domain, and the second dsRNA encodes a hypothetical protein. Genome sequence analysis revealed that the sequences of the dsRNA virus shared 99% identity with Bipolaris maydis botybirnavirus 1(BmBRV1) isolated from the causal agent of corn southern leaf blight, Bipolaris maydis. Hence, the dsRNA virus constitutes a new strain of BmBRV1 and was named Bipolaris maydis botybirnavirus 1 strain BdEW220 (BmBRV1-BdEW220). BmBRV1-BdEW220 contains spherical virions that are 37 nm in diameter and consist of two dsRNA segments. The structural proteins of the BmBRV1-BdEW220 virus particles were 110 kDa, 90 kDa, and 80 kDa and were encoded by dsRNA1 and 2-ORFs. Phylogenetic reconstruction indicated that BmBRV1 and BmBRV1-BdEW220 are phylogenetically related to the genus Botybirnavirus. Importantly, BmBRV1-BdEW220 influences the growth of B. dothidea and confers hypovirulence to the fungal host. To our knowledge, this is the first report of a botybirnavirus in B. dothidea.

Identification and Characterization of a Novel Hepta-Segmented dsRNA Virus From the Phytopathogenic Fungus Colletotrichum fructicola.

A novel hepta-segmented double-stranded RNA (dsRNA) virus was isolated and characterized from the strain FJ-4 of the phytopathogenic fungus Colletotrichum fructicola, and was named Colletotrichum fructicola chrysovirus 1 (CfCV1). The full-length cDNAs of dsRNA1-7 were 3620, 2801, 2687, 2437, 1750, 1536, and 1211 bp, respectively. The 5'- and 3'-untranslated regions of the seven dsRNAs share highly similar internal sequence and contain conserved sequence stretches, indicating that they have a common virus origin. The 5'-and 3'-UTRs of the seven dsRNAs were predicted to fold into stable stem-loop structures. CfCV1 contains spherical virions that are 35 nm in diameter consisting of seven segments. The largest dsRNA of CfCV1 encodes an RNA-dependent RNA polymerase (RdRp), and the second dsRNA encodes a viral capsid protein (CP). The dsRNA5 encodes a C2H2-type zinc finger protein containing an R-rich region and a G-rich region. The smallest dsRNA is a satellite-like RNA. The functions of the other proteins encoded by dsRNA3, dsRNA4, dsRNA6 are unknown. Phylogenetic analysis, based on RdRp and CP, indicated that CfCV1 is phylogenetically related to Botryosphaeria dothidea chrysovirus 1 (BdCV1), and Penicillium janczewskii chrysovirus 2 (PjCV2), a cluster of an independent cluster II group in the family Chrysoviridae. Importantly, all the seven segments of CfCV1 were transmitted successfully to other virus-free strains with an all-or-none fashion. CfCV1 exerts minor influence on the growth of C. fructicola but can confer hypovirulence to the fungal host. To our knowledge, this is the first report of a hepta-segmented tentative chrysovirus in C. fructicola.

Characterization of a novel double-stranded RNA mycovirus conferring hypovirulence from the phytopathogenic fungus Botryosphaeria dothidea.

A novel double-stranded RNA (dsRNA) virus, designated as Botryosphaeria dothidea RNA virus 1 (BdRV1), isolated from a hypovirulent strain YZN115 of Botryosphaeria dothidea was biologically and molecularly characterized. The genome of BdRV1 comprises of five dsRNAs. Each dsRNA contains a single open reading frame. The proteins encoded by dsRNA1-4 shared significant amino acid identities of 55%, 47%, 43% and 53% with the corresponding proteins of Aspergillus fumigatus tetramycovirus-1. DsRNA1, 3, and 4 of BdRV1 encoded an RNA-dependent RNA polymerase, a viral methyltransferase, and a P-A-S-rich protein, respectively. Function of proteins encoded by the dsRNA2 and dsRNA5 were unknown. BdRV1 conferred hypovirulence for its host and could be transmitted through conidia and hyphae contact.

Complete dsRNA sequence of a novel victorivirus isolated from the pear stem wart fungus Botryosphaeria dothidea.

Botryosphaeria dothidea is a pathogen that causes many important diseases of deciduous fruit trees worldwide. In this study, a double-stranded (ds) RNA of 5322 base pairs (bp) in length from strain GY25 of B. dothidea was isolated and sequenced. The dsRNA potentially contained two overlapping open reading frames (ORFs). The predicted gene product of ORF1 had the highest amino acid sequence similarity, 37 % (E-value, 8e(-101)), to the capsid protein of Rosellinia necatrix victorivirus 1 (RnV1), and ORF2 had the highest similarity, 44 % (E-value, 0.0), to the RNA-directed RNA polymerase of Beauveria bassiana victorivirus NZL/1980(BbV-NZL/1980). Both of these viruses are members of the genus Victorivirus in the family Totiviridae. There was a small ORF at the 5' terminus whose predicted gene product did not show homology to any known proteins. The dsRNA from B. dothidea strain GY25 appears to be a genomic component of a victorivirus, which we have tentatively named "Botryosphaeria dothidea victorivirus 1" (BdV1). This is the first full-length genome sequence of a putative victorivirus infecting B. dothidea.

Biological and Molecular Characterization of Four Botryosphaeria Species Isolated from Pear Plants Showing Stem Wart and Stem Canker in China.

Pear stem wart and pear stem canker, which have been considered as two different fungal diseases caused by pathogens belonging to Botryosphaeria spp., commonly occur and cause serious damage in the main pear-producing areas in China. To identify the species of this genus infecting pear in China, 131 Botryosphaeria isolates were recovered from pear samples exhibiting symptoms collected from 20 different provinces and areas. Morphological characterization and phylogenetic analyses of the ribosomal DNA internal transcribed spacer region and the ß-tubulin and EF1-α genes revealed that Botryosphaeria dothidea, B. rhodina, B. obtusa, and B. parva were associated with different pear stem wart and stem canker symptoms. Remarkably, all isolates of B. dothidea were obtained from the samples showing either stem wart or stem canker lesions; however, the isolates of the other three species were obtained only from the samples showing stem canker. Pathogenicity tests on the pear shoots showed that B. dothidea isolates could induce stem wart or stem canker lesions but all the isolates of the other three species could only induce stem cankers. However, the isolates of B. parva, B. rhodina, and B. obtusa exhibited higher virulence than that of the B. dothidea isolates on the pear fruit. Our results suggest that B. dothidea is the common causal agent for these two diseases (a pear stem wart and a pear-related stem canker), whereas B. parva, B. rhodina, and B. obtusa only cause pear stem canker diseases. To our knowledge, this study represents the first report for biological and molecular characterization of four Botryosphaeria spp. isolated from pear plants showing stem wart and stem canker in China.

Astrocyte elevated gene-1 induces breast cancer proliferation and invasion through upregulating HER2/neu expression.

BACKGROUND: Astrocyte elevated gene-1 (AEG-1), primarily identified as a late response gene induced by HIV-1 infection, plays multiple roles in the process of oncogenesis. This novel gene has been demonstrated to be involved in the several potent carcinogenic pathways, including PI3K/Akt pathway, nuclear factor (NF)-κB pathway, and Wnt/κ-catenin pathway. Although the function of AEG-1 has been intensively investigated in recent years, the molecular mechanism underlying its oncogenic role is largely unknown. The aim of this research was to explore the potential function of AEG-1 in breast cancer development and progression. METHODS: AEG-1 was ectopically overexpressed in breast cancer MCF-7 cells and its biological effects on the proliferation and invasion of MCF-7 cells were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and invasion assays. The expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis, was also determined. RESULTS: Overexpression of the AEG-1 promoted the proliferation and invasion ability of breast cancer cells, and upregulated the expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis. CONCLUSION: AEG-1 might facilitate the proliferation and invasion of breast cancer cells by upregulating HER2/neu expression, which provides a potential target for breast cancer therapy.

[Measurement of sperm DNA integrity by sperm chromatin dispersion test and TdT-mediated dUTP nick end labeling assay].

OBJECTIVE: To compare the effects of sperm chromatin dispersion (SCD) test and TdT-mediated dUTP nick end labeling (TUNEL) assay in assessing the DNA fragmentation in human sperm. METHODS: Motile sperms were isolated from the semen samples obtained from 20 healthy fertile men and 32 clinically infertile patients by swim-up technique, and underwent SCD and TUNEL to analyze the DNA fragmentation. RESULTS: The rate of sperm with DNA damage of the infertile patients was 12.8% +/- 5.8% tested by SCD, significantly higher than that of the healthy fertile men (7.6% +/- 3.3%, t = 3.576, P = 0.001), and the rate of sperm with DNA damage of the infertile patients was 11.1% +/- 5.1% tested by TUNEL assay, significantly higher than that of the healthy fertile men (6.8% +/- 2.8%, t = 3.467, P = 0.001). The proportion of sperm cell with abnormal DNA integrity measured by SCD test was correlated strongly with that determined by TUNEL for the infertile men (r = 0.841, P = 0.000) and for the fertile men too (r = 0.823, P = 0.000). The rate of sperm with DNA damage measured by SCD were not significantly different from those of TUNEL-positive sperm in fertile men (t = 1.996, P = 0.060). The rate of sperm with DNA damage measured by SCD was significantly higher than that measured by TUNEL among infertile patients (t = 3.023, P = 0.005). CONCLUSION: The presence of sperm DNA damage may lead to male infertility. SCD is simpler, cheaper and more reliable than TUNEL in testing the sperm DNA damage.