Background dementia has been a major public health problem. However, there has not yet been a nationwide investigation or systematic analysis of the prevalence of dementia in China from 1980 to 2004. Objectives the aim of this study was to analyse the prevalence of dementia and its major subtypes [Alzheimer disease (AD), vascular dementia (VD)] among the population aged 60 years and older in China from 1980 to 2004. Methods epidemiological investigations on dementia in China published in journals and covering the period from 1980 to 2004 were identified manually and on-line by using CBMDISK, Chongqing VIP database and CNKI database. Those reported in English journals were identified using MEDLINE. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity. Results twenty-five studies were selected, the statistical information of which was collected for systematic analysis. Our results showed that AD and VD were the two major subtypes of dementia in China, and the pooled prevalence of AD and VD for the population aged 60 years and older was 1.6 and 0.8%, respectively. There was a higher prevalence of AD in the illiterate elderly population (3.2%) than in those who received years of education. The chronological prevalence of AD increased significantly from 1980 to 2004. In southern and northern China, the prevalence of AD was 2.0 and 1.2%, respectively, while VD was 0.6 and 1.1%, respectively. Conclusions in the last 24 years, AD and VD were the two major subtypes of dementia in China. The prevalence of AD may be affected by sex, education, occupation or age. The prevalence of VD, which was higher in northern than in southern China, seems not to be affected by age, sex or education.

Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry.

Two types of carbon dots were prepared by using the powder of young barley leaves as the precursor, which have the capability of selective cell imaging and antiviral activity.

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins.

Tumor development has long been known to resemble abnormal embryogenesis. The ESC self-renewal gene NANOG is purportedly expressed in some epithelial cancer cells and solid tumors, but a casual role in tumor development has remained unclear. In order to more comprehensively elucidate the relationship between human Nanog and tumorigenesis, the hNanog was ectopically expressed in the 293 cell line to investigate its potential for malignant transformation of cells both in vitro and in vivo. Here we provide compelling evidence that the overexpression of hNanog resulted in increased cell proliferation, anchor-independent growth in soft agar, and formation of tumors after subcutaneous injection of athymic nude mice. Pathologic analysis revealed that these tumors were poorly differentiated. In analysis of the underlying molecular mechanism, two proteins, FAK and Ezrin, were identified to be upregulated in the hNanog expressing 293 cells. Our results demonstrate that hNanog is a potent human oncogene and has the ability to induce cellular transformation of human cells.

Stress granules (SGs) are sites of mRNA storage that are formed in response to various conditions of stress, including viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. In this study, we found that infection of PRRSV strain WUH3 (genotype 2 PRRSV) induced stable formation of robust SGs in MARC-145 cells, as demonstrated by the recruitment of marker proteins of SGs, including TIA1, G3BP1, and eIF3η. Treatment with specific inhibitors or siRNAs against the stress kinases that are involved in SG formation revealed that PRRSV induced SG formation through a PERK (protein kinase R–like endoplasmic reticulum kinase)-dependent mechanism. Impairment of SG assembly by concomitant knockdown of the SG marker proteins (TIA1, G3BP1, and TIAR) did not affect PRRSV growth, while significantly enhanced PRRSV-induced NF-κB subunit p65 phosphorylation and inflammatory cytokine production. Taken together, our results demonstrate that PRRSV induces SG formation via a PERK-dependent pathway and that SGs are involved in the signaling pathway of the PRRSV-induced inflammatory response in MARC-145 cells.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The nonstructural protein nsp5, also called 3C-like protease, is responsible for processing viral polyprotein precursors in coronavirus (CoV) replication. Previous studies have shown that PDCoV nsp5 cleaves the NF-κB essential modulator and the signal transducer and activator of transcription 2 to disrupt interferon (IFN) production and signaling, respectively. Whether PDCoV nsp5 also cleaves IFN-stimulated genes (ISGs), IFN-induced antiviral effector molecules, remains unclear. In this study, we screened 14 classical ISGs and found that PDCoV nsp5 cleaved the porcine mRNA-decapping enzyme 1a (pDCP1A) through its protease activity. Similar cleavage of endogenous pDCP1A was also observed in PDCoV-infected cells. PDCoV nsp5 cleaved pDCP1A at glutamine 343 (Q343), and the cleaved pDCP1A fragments, pDCP1A1–343 and pDCP1A344–580, were unable to inhibit PDCoV infection. Mutant pDCP1A-Q343A, which resists nsp5-mediated cleavage, exhibited a stronger ability to inhibit PDCoV infection than wild-type pDCP1A. Interestingly, the Q343 cleavage site is highly conserved in DCP1A homologs from other mammalian species. Further analyses demonstrated that nsp5 encoded by seven tested CoVs that can infect human or pig also cleaved pDCP1A and human DCP1A, suggesting that DCP1A may be the common target for cleavage by nsp5 of mammalian CoVs. IMPORTANCE Interferon (IFN)-stimulated gene (ISG) induction through IFN signaling is important to create an antiviral state and usually directly inhibits virus infection. The present study first demonstrated that PDCoV nsp5 can cleave mRNA-decapping enzyme 1a (DCP1A) to attenuate its antiviral activity. Furthermore, cleaving DCP1A is a common characteristic of nsp5 proteins from different coronaviruses (CoVs), which represents a common immune evasion mechanism of CoVs. Previous evidence showed that CoV nsp5 cleaves the NF-κB essential modulator and signal transducer and activator of transcription 2. Taken together, CoV nsp5 is a potent IFN antagonist because it can simultaneously target different aspects of the host IFN system, including IFN production and signaling and effector molecules.

Gold nanoclusters (Au NCs) are widely used in biological imaging and antitumor treatment because of their excellent cell membrane permeability, good fluorescence properties, and high biocompatibility. However, their effects on viruses are still largely unknown. Here, pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) were used respectively as the models of DNA virus and RNA virus to investigate the influences of glutathione-stabilized fluorescent Au NCs on viruses by plaque assay, indirect immunofluorescence assay, quantitative real-time polymerase chain reaction assay, and Western blot assay. The experimental data indicated that Au NCs selectively inhibited proliferation and protein expression of PRRSV but not that of PRV. Mechanistically, Au NCs directly inactivated PRRSV and blocked viral adsorption but showed no effect on viral genome replication. These findings prompt the possibility of developing Au NCs as an effective specific antiviral nanomaterial against RNA virus infection in the future.