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.
Click here to view the accompanying paper in this issue. Videocasts of this article are available in: English: http://player.polyv.net/videos/player.swf?vid=f6ee5715d9808c7a481b7ae727da00dd_f Mandarin: http://player.polyv.net/videos/f6ee5715d98ae743a9b0509d0900c91f_f.swf
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.
High-energy photons from the Crab Nebula
The Crab Nebula contains a pulsar that excites the surrounding gas to emit high-energy radiation. The combination of the pulsar's youth and nearby location ...makes the nebula the brightest gamma-ray source in the sky. The LHAASO Collaboration report observations of this source at energies of tera– to peta–electron volts, extending the spectrum of this prototypical object. They combine these data with observations at lower energies to model the physics of the emission process. The multiwave-length data can be explained by a combination of synchrotron radiation and inverse Compton scattering.
Science
, abg5137, this issue p.
425
Detection of the Crab Nebula at peta–electron volt energies constrains the gamma-ray emission mechanism.
The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar’s rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10
−4
to 1.1 peta–electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta–electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron’s size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta–electron volt electrons, 2.5 × 10
36
ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta–electron volt protons to the production of the highest-energy gamma rays.
Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory ...(LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
Fast radio bursts (FRBs) are millisecond-duration radio transients
of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star ...magnetospheres
or relativistic shocks far from the central energy source
. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters
or variable polarization angles in some other apparently one-off events
. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.
Abstract
The intertwining between spin, charge, and lattice degrees of freedom can give rise to unusual macroscopic quantum states, including high-temperature superconductivity and quantum anomalous ...Hall effects. Recently, a charge density wave (CDW) has been observed in the kagome antiferromagnet FeGe, indicative of possible intertwining physics. An outstanding question is that whether magnetic correlation is fundamental for the spontaneous spatial symmetry breaking orders. Here, utilizing elastic and high-resolution inelastic x-ray scattering, we observe a c-axis superlattice vector that coexists with the 2
$$\times$$
×
2
$$\times$$
×
1 CDW vectors in the kagome plane. Most interestingly, between the magnetic and CDW transition temperatures, the phonon dynamical structure factor shows a giant phonon-energy hardening and a substantial phonon linewidth broadening near the c-axis wavevectors, both signaling the spin-phonon coupling. By first principles and model calculations, we show that both the static spin polarization and dynamic spin excitations intertwine with the phonon to drive the spatial symmetry breaking in FeGe.
An anomaly in differential scanning calorimetry has been reported in a number of metallic glass materials in which a broad exothermal peak was observed between the glass and crystallization ...temperatures. The mystery surrounding this calorimetric anomaly is epitomized by four decades long studies of Pd-Ni-P metallic glasses, arguably the best glass-forming alloys. Here we show, using a suite of in situ experimental techniques, that Pd-Ni-P alloys have a hidden amorphous phase in the supercooled liquid region. The anomalous exothermal peak is the consequence of a polyamorphous phase transition between two supercooled liquids, involving a change in the packing of atomic clusters over medium-range length scales as large as 18 Å. With further temperature increase, the alloy reenters the supercooled liquid phase, which forms the room-temperature glass phase on quenching. The outcome of this study raises a possibility to manipulate the structure and hence the stability of metallic glasses through heat treatment.
Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.