Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
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The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
China's seas cover nearly 5 million square kilometers extending from the tropical to the temperate climate zones and bordering on 32,000 km of coastline, including islands. Comprehensive systematic ...study of the marine biodiversity within this region began in the early 1950s with the establishment of the Qingdao Marine Biological Laboratory of the Chinese Academy of Sciences. Since that time scientists have carried out intensive multidisciplinary research on marine life in the China seas and have recorded 22,629 species belonging to 46 phyla. The marine flora and fauna of the China seas are characterized by high biodiversity, including tropical and subtropical elements of the Indo-West Pacific warm-water fauna in the South and East China seas, and temperate elements of North Pacific temperate fauna mainly in the Yellow Sea. The southern South China Sea fauna is characterized by typical tropical elements paralleled with the Philippine-New Guinea-Indonesia Coral triangle typical tropical faunal center. This paper summarizes advances in studies of marine biodiversity in China's seas and discusses current research mainly on characteristics and changes in marine biodiversity, including the monitoring, assessment, and conservation of endangered species and particularly the strengthening of effective management. Studies of (1) a tidal flat in a semi-enclosed embayment, (2) the impact of global climate change on a cold-water ecosystem, (3) coral reefs of Hainan Island and Xisha-Nansha atolls, (4) mangrove forests of the South China Sea, (5) a threatened seagrass field, and (6) an example of stock enhancement practices of the Chinese shrimp fishery are briefly introduced. Besides the overexploitation of living resources (more than 12.4 million tons yielded in 2007), the major threat to the biodiversity of the China seas is environmental deterioration (pollution, coastal construction), particularly in the brackish waters of estuarine environments, which are characterized by high productivity and represent spawning and nursery areas for several economically important species. In the long term, climate change is also a major threat. Finally, challenges in marine biodiversity studies are briefly discussed along with suggestions to strengthen the field. Since 2004, China has participated in the Census of Marine Life, through which advances in the study of zooplankton and zoobenthos biodiversity were finally summarized.
Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from ...astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Summary
Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide‐binding, oligomerization domain (NOD)‐like receptor family, ...pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2‐biased response. In this study, VDR–/– mice and WT (WT) mice were used. Th2 cell differentiation between VDR–/– mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR–/– mice. The VDR–/–CD4+ T cells were prone to Th2 polarization. VDR–/– mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR–/– mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.
VDR expression is lower in CD4+ T cells of FA patients; VDR is negatively correlated with Th2 cytokines in CD4+ T cells of FA patients
Face-centered-cubic (fcc) type high entropy alloys (HEAs) exhibit outstanding ductility even at the liquid nitrogen temperature, but they are relatively weak in strength which is far from the ...requirements for practical structural applications. One of the general concepts employed previously in alloy design is the suppression of ‘brittle’ intermetallic compound formation which usually leads to a serious embrittlement. Surprisingly, we reveal in this study that the precipitation of hard σ and μ intermetallic compounds tremendously strengthened the CoCrFeNiMo0.3 HEA but without causing a serious embrittlement. It exhibits a tensile strength as high as 1.2 GPa and a good ductility of ∼19%. A careful study of the deformation behavior reveals that the fcc matrix exhibits an extremely high work hardening exponent of 0.75, which suppresses the propagation of microcracks originated at these brittle particles. Our work presents a very successful demonstration of using complex hard intermetallic particles to manipulate the properties of fcc-type HEA systems. Furthermore, lattice distortion has been carefully measured in powder-metallurgy materials by line broadening from X-ray diffraction (XRD). It is interesting to discover that lattice planes are highly distorted in HEAs and this distortion also contributes to solid solution hardening.
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The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray ...observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.
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