Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically significant pathogen that has adversely affected China's swine industry. Currently, a novel type 2 PRRSV, ...called the NADC30‐like strain, is epidemic in numerous provinces of China, and commercial vaccines provide limited protection for infected animals. The extensive recombination phenomenon among NADC30‐like PRRSVs is identified as a unique molecular characteristic of the virus. However, our understanding of how recombination influences NADC30‐like PRRSVs is largely inadequate. In this study, we analysed the genetic characteristics of a recombinant NADC30‐like PRRSV (SC‐d) and examined its pathogenicity compared with a non‐recombinant NADC30‐like PRRSV (SD‐A19) and a highly pathogenic PRRSV (HuN4). SC‐d has three discontinuous deletions in nsp2, consistent with NADC30 isolated from the United States in 2008. Furthermore, we identified four recombination breakpoints in the SC‐d genome, which separated the SC‐d genome into four regions (regions A, B, C and D). Regions A and C are closely related to the JXA1‐like strain, one of the earliest Chinese HP‐PRRSV strains, and regions B and D are closely related to the NADC30 strain. Moreover, SC‐d inoculated piglets exhibited a persistent fever, moderate weight loss, mild thymus atrophy and obvious microscopic lung lesions. In summary, the recombinant NADC30‐like PRRSV SC‐d strain displayed a higher pathogenicity than the non‐recombinant NADC30‐like PRRSV SD‐A19 strain; however, the pathogenicity of the NADC30‐like PRRSV SC‐d was lower compared with the HP‐PRRSV HuN4 strain in piglets. Our findings demonstrate that recombination is responsible for the enormous genetic diversity and pathogenicity variance of the NADC30‐like PRRSV in China. This study provides a theoretical basis for developing a more reasonable PRRSV control and prevention strategy.
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
This study aims at investigating the effects of MSW incinerator fly ash (FA) and bottom ash (BA) on the anaerobic co-digestion of OFMSW with FA or BA. It also simulates the biogas production from ...various dosed and control bioreactors. Results showed that suitable ashes addition (FA/MSW 10 and 20
g
L
−1 and BA/MSW 100
g
L
−1) could improve the MSW anaerobic digestion and enhance the biogas production rates. FA/MSW 20
g
L
−1 bioreactor had the higher biogas production and rate implying the potential option for MSW anaerobic co-digestion. Modeling studies showed that exponential plot simulated better for FA/MSW 10
g
L
−1 and control bioreactors while Gaussian plot was applicable for FA/MSW 20
g
L
−1 one. Linear and exponential plot of descending limb both simulated better for BA/MSW 100
g
L
−1 bioreactor. Modified Gompertz plot showed higher correlation of biogas accumulation than exponential rise to maximum plot for all bioreactors.
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
The X-linked
Foxp3 is a member of the forkhead/winged helix transcription factor family. Germline mutations cause lethal autoimmune diseases in males. Serendipitously, we observed that female mice ...heterozygous for the “scurfin” mutation of the
Foxp3 gene (
Foxp3
sf/+) developed cancer at a high rate. The majority of the cancers were mammary carcinomas in which the wild-type
Foxp3 allele was inactivated and
HER-2/ErbB2 was overexpressed. Foxp3 bound and repressed the
HER-2/
ErbB2 promoter. Deletion, functionally significant somatic mutations, and downregulation of the
FOXP3 gene were commonly found in human breast cancer samples and correlated significantly with HER-2/ErbB2 overexpression, regardless of the status of
HER-2 amplification. Our data demonstrate that
FOXP3 is an X-linked breast cancer suppressor gene and an important regulator of the
HER-2/ErbB2 oncogene.
Abstract
Unconventional superconductors often feature competing orders, small superfluid density, and nodal electronic pairing. While unusual superconductivity has been proposed in the kagome metals
...A
V
3
Sb
5
, key spectroscopic evidence has remained elusive. Here we utilize pressure-tuned and ultra-low temperature muon spin spectroscopy to uncover the unconventional nature of superconductivity in RbV
3
Sb
5
and KV
3
Sb
5
. At ambient pressure, we observed time-reversal symmetry breaking charge order below
$${T}_{{{\rm{1}}}^{*}\simeq$$
T
1
*
≃
110 K in RbV
3
Sb
5
with an additional transition at
$${T}_{{{\rm{2}}}^{*}\simeq$$
T
2
*
≃
50 K. Remarkably, the superconducting state displays a nodal energy gap and a reduced superfluid density, which can be attributed to the competition with the charge order. Upon applying pressure, the charge-order transitions are suppressed, the superfluid density increases, and the superconducting state progressively evolves from nodal to nodeless. Once optimal superconductivity is achieved, we find a superconducting pairing state that is not only fully gapped, but also spontaneously breaks time-reversal symmetry. Our results point to unprecedented tunable nodal kagome superconductivity competing with time-reversal symmetry-breaking charge order and offer unique insights into the nature of the pairing state.
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
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