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
Agyrotropic electron distributions are frequently taken as an indicator of electron diffusion regions of magnetic reconnection. However, they have also been found at electron‐scale boundaries of the ...non‐reconnecting magnetopause and are generated by the electron finite gyroradius effect. Here, we present magnetospheric multiscale observations of agyrotropic electron distributions in the foreshock region. These distributions are generated by the electron finite gyroradius effect after magnetic curvature scattering at a thin electron‐scale boundary. Meanwhile, the signatures of magnetic reconnection are absent at this boundary. The test‐particle simulation is adopted to verify the generation of the agyrotropic electron distributions by assuming one‐dimensional magnetic geometry. These observations suggest that agyrotropic electron distributions can be more widely formed at electron‐scale boundaries in space plasma environment.
Plain Language Summary
The agyrotropic electron distributions, which could be unstable to generate high frequency electrostatic waves, reveal valuable information of electron dynamics at electron scales. However, due to electron's small mass, the related observational study becomes only possible with the high‐resolution magnetospheric multiscale data. In this study, we show that the agyrotropic electron distributions can be also formed in the foreshock transients such as inside an hot flow anomaly, suggesting that agyrotropic electron distributions are ubiquitous in space plasma.
Key Points
We present the first magnetospheric multiscale observations of agyrotropic electron distributions in the foreshock transients
Accompanied with the agytropic electron distributions, clear signatures of magnetic reconnection are absent
The agytropic electron distributions are formed by the electron finite gyroradius effect at electron‐scale boundaries
We present the first finding of continental crust-derived Precambrian zircons in garnet/spinel pyroxenite veins within mantle xenoliths carried by the Neogene Hannuoba basalt in the central zone of ...the North China Craton (NCC). Petrological and geochemical features indicate that these mantle-derived composite xenoliths were formed by silicic melt–lherzolite interaction. The Precambrian zircon ages can be classified into three age groups of 2·4–2·5 Ga, 1·6–2·2 Ga and 0·6–1·2 Ga, coinciding with major geological events in the NCC. These Precambrian zircons fall in the field of continental granitoid rocks in plots of U/Yb vs Hf and Y. Their igneous-type REE patterns and metamorphic zircon type CL images indicate that they were not crystallized during melt–peridotite interaction and subsequent high-pressure metamorphism. The ∼2·5 Ga zircons have positive εHf(t) values (2·9–10·6), whereas the younger Precambrian zircons are dominated by negative εHf(t) values, indicating an ancient continental crustal origin. These observations suggest that the Precambrian zircons were xenocrysts that survived melting of recycled continental crustal rocks and were then injected with silicate melt into the host peridotite. In addition to the Precambrian zircons, igneous zircons of 315 ± 3 Ma (2σ), 80–170 Ma and 48–64 Ma were separated from the garnet/spinel pyroxenite veins; these provide evidence for lower continental crust and oceanic crust recycling-induced multi-episodic melt–peridotite interactions in the central zone of the NCC. The combination of the positive εHf(t) values (2·91–24·6) of the 315 Ma zircons with the rare occurrence of 302–324 Ma subduction-related diorite–granite plutons in the northern margin of the NCC implies that the 315 Ma igneous zircons might record melt–peridotite interactions in the lithospheric mantle induced by Palaeo-Asian oceanic crust subduction. Igneous zircons of age 80–170 Ma generally coexist with the Precambrian metamorphic zircons and have lower Ce/Yb and Th/U ratios, higher U/Yb ratios and greater negative Eu anomalies. The εHf(t) values of these zircons vary greatly from –47·6 to 24·6. The 170–110 Ma zircons are generally characterized by negative εHf(t) values, whereas the 110–100 Ma zircons have positive εHf(t) values. These observations suggest that melt–peridotite interactions at 80–170 Ma were induced by partial melting of recycled continental crust. The 48–64 Ma igneous zircons are characterized by negligible Ce anomalies, unusually high REE, U and Th contents, and positive εHf(t) values. These features imply that the melt–peridotite interactions at 48–64 Ma could be associated with a depleted mantle-derived carbonate melt or fluid.
In this study, we investigate detailed electron dynamics in strong guide‐field reconnection (the normalized guide field is ∼1.5). This reconnection event is observed by the Magnetospheric Multiscale ...(MMS) spacecraft at the center of a flux rope in the magnetotail. With the presence of a large parallel electric field (E‖) in the electron current sheet, electrons are accelerated when streaming into this E‖ region from one direction, and decelerated from the other direction. Some decelerated electrons can reduce the parallel speed to ∼0 to form relatively isotropic electron distributions at one side of the electron current sheet, as the estimated acceleration potential satisfies the relation eΦ‖ ≥ kTe,‖, where Te,‖ is the electron temperature parallel to the magnetic field. Therefore, a large E‖ is generated to balance the parallel electron pressure gradient across the electron current sheet, since electrons at the other side of the current sheet are still anisotropic. Based on these observations, we further show that the electron beta is an important parameter in guide‐field reconnection, providing a new perspective to solve the large parallel electric field puzzle in guide‐field reconnection.
Plain Language Summary
Magnetic reconnection is a universal process that rapidly converts energy from the magnetic field to plasma. The energy conversion at kinetic scales is of particular interest to researchers, as it is directly related to reconnection process in the central diffusion region. In general, the reconnecting magnetic fields do not have to be antiparallel, and an additional magnetic component known as the guide field (Bg) can appear in the direction perpendicular to the reconnecting plane. Recently, observations from Magnetospheric Multiscale (MMS) mission show a large electric field parallel to the local magnetic field, which is several times larger than the reconnection electric field, can appear in guide‐field reconnection, and impact electrons significantly. However, the generation of this large parallel electric field in strong guide‐field reconnection is still not fully understood. In this study, we suggest that the electron beta (ratio of the electron thermal pressure to the magnetic pressure) is an important parameter in guide‐field reconnection. Only within some proper electron beta range, a parallel pressure gradient across the electron current sheet can form to balance the large parallel electric field.
Key Points
We present detailed electron dynamics in guide‐field reconnection at the center of a flux rope
With eΦ‖ ≥ kTe,‖, the observed electron behaviors can be well explained
We suggest that electron beta is an important parameter for the generation of a large parallel electric field in guide‐field reconnection
Growing evidence suggests that vascular risk factors (VRF) contribute to cognitive decline. The aim of this study was to investigate the impact of VRF on the conversion from mild cognitive impairment ...(MCI) to Alzheimer disease (AD) dementia.
A total of 837 subjects with MCI were enrolled at baseline and followed up annually for 5 years. The incidence of AD dementia was investigated. A mixed random effects regression model was used to analyze the association between VRF and the progression of MCI assessed with Mini-Mental State Examination and instrumental Activities of Daily Living. Cox proportional hazard models were used to identify the association between VRF and dementia conversion, and to examine whether treatment of VRF can prevent dementia conversion.
At the end of the follow-up, 298 subjects converted to AD dementia, while 352 remained MCI. Subjects with VRF had a faster progression in cognition and function relative to subjects without. VRF including hypertension, diabetes, cerebrovascular diseases, and hypercholesterolemia increased the risk of dementia conversion. Those subjects with MCI in whom all VRF were treated had a lower risk of dementia than those who had some VRF treated. Treatment of individual VRF including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of AD conversion.
VRF increased the risk of incident AD dementia. Treatment of VRF was associated with a reduced risk of incident AD dementia. Although our findings are observational, they suggest active intervention for VRF might reduce progression in MCI to AD dementia.
The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria ...and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo. The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.
Refractory high‐entropy alloys (RHEAs) show promising applications at high temperatures. However, achieving high strengths at elevated temperatures above 1173K is still challenging due to heat ...softening. Using intrinsic material characteristics as the alloy‐design principles, a single‐phase body‐centered‐cubic (BCC) CrMoNbV RHEA with high‐temperature strengths (beyond 1000 MPa at 1273 K) is designed, superior to other reported RHEAs as well as conventional superalloys. The origin of the high‐temperature strength is revealed by in situ neutron scattering, transmission‐electron microscopy, and first‐principles calculations. The CrMoNbV's elevated‐temperature strength retention up to 1273 K arises from its large atomic‐size and elastic‐modulus mismatches, the insensitive temperature dependence of elastic constants, and the dominance of non‐screw character dislocations caused by the strong solute pinning, which makes the solid‐solution strengthening pronounced. The alloy‐design principles and the insights in this study pave the way to design RHEAs with outstanding high‐temperature strength.
Structural materials with exceptional high‐temperature strengths are highly desirable for high‐temperature applications. In this work, three alloy‐design principles of the large atomic‐size and elastic‐modulus mismatches, the insensitive temperature‐dependence of elastic properties, and the dominance of non‐screw dislocations are used to design a CrMoNbV refractory high‐entropy alloy, which exhibits outperforming high‐temperature strengths.
Bacterial infections on the implant surface may eventually lead to biofilm formation and thus threaten the use of implants in body. Despite efficient host immune system, the implant surface can be ...rapidly occupied by bacteria, resulting in infection persistence, implant failure, and even death of the patients. It is difficult to cope with these problems because bacteria exhibit complex adhesion mechanisms to the implants that vary according to bacterial strains. Different biomaterial coatings have been produced to release antibiotics to kill bacteria. However, antibiotic resistance occurs very frequently. Stimuli-responsive biomaterials have gained much attention in recent years but are not effective enough in killing the pathogens because of the complex mechanisms in bacteria. This review is focused on the development of highly efficient and specifically targeted biomaterials that release the antimicrobial agents or respond to bacteria on demands in body. The mechanisms of bacterial adhesion, biofilm formation, and antibiotic resistance are discussed, and the released substances accounting for implant infection are described. Strategies that have been used in past for the eradication of bacterial infections are also discussed. Different types of stimuli can be triggered only upon the existence of bacteria, leading to the release of antibacterial molecules that in turn kill the bacteria. In particular, the toxin-triggered, pH-responsive, and dual stimulus-responsive adaptive antibacterial biomaterials are introduced. Finally, the state of the art in fabrication of dual responsive antibacterial biomaterials and tissue integration in medical implants is discussed.
PDF
