In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
In conventional superconductors, the electron pairing that allows superconductivity is caused by exchange of virtual phonons, which are quanta of lattice vibration. For high-transition-temperature ...(high-Tc) superconductors, it is far from clear that phonons are involved in the pairing at all. For example, the negligible change in Tc of optimally doped Bi2Sr2CaCu2O8+δ (Bi2212; ref. 1) upon oxygen isotope substitution (16O → 18O leads to Tc decreasing from 92 to 91 K) has often been taken to mean that phonons play an insignificant role in this material. Here we provide a detailed comparison of the electron dynamics of Bi2212 samples containing different oxygen isotopes, using angle-resolved photoemission spectroscopy. Our data show definite and strong isotope effects. Surprisingly, the effects mainly appear in broad high-energy humps, commonly referred to as 'incoherent peaks'. As a function of temperature and electron momentum, the magnitude of the isotope effect closely correlates with the superconducting gap-that is, the pair binding energy. We suggest that these results can be explained in a dynamic spin-Peierls picture, where the singlet pairing of electrons and the electron-lattice coupling mutually enhance each other.
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.
Purpose
To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial ...chemoembolization (cTACE) treatments.
Methods
367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1–2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments.
Results
There was no difference in complete response (CR) (
P
= 0.671) and objective response rate (ORR) (
P
= 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (
P
= 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1–3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1–3 month post-DEB-TACE (
P
= 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (
P
= 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups.
Conclusion
DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.
Biodegradable synthetic scaffolds hold great promise for oral and craniofacial guided tissue regeneration and bone regeneration. To overcome the limitations of current scaffold materials in terms of ...osteogenic and antimicrobial properties, we have developed a novel silver-modified/collagen-coated electrospun poly-lactic-co-glycolic acid/polycaprolactone (PLGA/PCL) scaffold (PP-pDA-Ag-COL) with improved antimicrobial and osteogenic properties. Our novel scaffold was generated by electrospinning a basic PLGA/PCL matrix, followed by silver nanoparticles (AgNPs) impregnation via in situ reduction, polydopamine coating, and then coating by collagen I. The three intermediate materials involved in the fabrication of our scaffolds, namely, PLGA/PCL (PP), PLGA/PCL-polydopamine (PP-pDA), and PLGA/PCL-polydopamine-Ag (PP-pDA-Ag), were used as control scaffolds. Scanning electron micrographs and mechanical testing indicated that the unique three-dimensional structures with randomly oriented nanofibrous electrospun scaffold architectures, the elasticity modulus, and the tensile strength were maintained after modifications. CCK-8 cell proliferation analysis demonstrated that the PP-pDA-Ag-COL scaffold was associated with higher MC3T3 proliferation rates than the three control scaffolds employed. Scanning electron and fluorescence light microscopy illustrated that PP-pDA-Ag-COL scaffolds significantly enhanced MC3T3 cell adhesion compared to the control scaffolds after 12 and 24 h culture, in tandem with the highest β1 integrin expression levels, both at the mRNA level and the protein level. Alkaline phosphatase activity, BMP2, and RUNX2 expression levels of MC3T3 cells cultured on PP-pDA-Ag-COL scaffolds for 7 and 14 days were also significantly higher when compared to controls (P < 0.001). There was a wider antibacterial zone associated in PP-pDA-Ag-COL and PP-pDA-Ag scaffolds versus control scaffolds (P < 0.05), and bacterial fluorescence was reduced on the Ag-modified scaffolds after 24 h inoculation against Staphylococcus aureus and Streptococcus mutans. In a mouse periodontal disease model, the PP-pDA-Ag-COL scaffold enhanced alveolar bone regeneration (31.8%) and was effective for periodontitis treatment. These results demonstrate that our novel PP-pDA-Ag-COL scaffold enhanced biocompatibility and osteogenic and antibacterial properties and has therapeutic potential for alveolar/craniofacial bone regeneration.
Graphene has shown great application potential as the host material for next-generation electronic devices. However, despite its intriguing properties, one of the biggest hurdles for graphene to be ...useful as an electronic material is the lack of an energy gap in its electronic spectra. This, for example, prevents the use of graphene in making transistors. Although several proposals have been made to open a gap in graphene's electronic spectra, they all require complex engineering of the graphene layer. Here, we show that when graphene is epitaxially grown on SiC substrate, a gap of approximately 0.26 eV is produced. This gap decreases as the sample thickness increases and eventually approaches zero when the number of layers exceeds four. We propose that the origin of this gap is the breaking of sublattice symmetry owing to the graphene-substrate interaction. We believe that our results highlight a promising direction for bandgap engineering of graphene.
Fresh meat is a highly perishable product due to its biological composition. Many interrelated factors influence the shelf life and freshness of meat such as holding temperature, atmospheric oxygen ...(O
2), endogenous enzymes, moisture, light and most importantly, micro-organisms. With the increased demand for high quality, convenience, safety, fresh appearance and an extended shelf life in fresh meat products, alternative non-thermal preservation technologies such as high hydrostatic pressure, superchilling, natural biopreservatives and active packaging have been proposed and investigated. Whilst some of these technologies are efficient at inactivating the micro-organisms most commonly related to food-borne diseases, they are not effective against spores. To increase their efficacy against vegetative cells, a combination of several preservation technologies under the so-called hurdle concept has also been investigated. The objective of this review is to describe current methods and developing technologies for preserving fresh meat. The benefits of some new technologies and their industrial limitations is presented and discussed.
We investigate theoretically the Landau levels (LLs) and magneto-transport properties of phosphorene under a perpendicular magnetic field within the framework of the effective k·p Hamiltonian and ...tight-binding (TB) model. At low field regime, we find that the LLs linearly depend both on the LL index n and magnetic field B, which is similar with that of conventional semiconductor two-dimensional electron gas. The Landau splittings of conduction and valence band are different and the wavefunctions corresponding to the LLs are strongly anisotropic due to the different anisotropic effective masses. An analytical expression for the LLs in low energy regime is obtained via solving the decoupled Hamiltonian, which agrees well with the numerical calculations. At high magnetic regime, a self-similar Hofstadter butterfly (HB) spectrum is obtained by using the TB model. The HB spectrum is consistent with the LL fan calculated from the effective k·p theory in a wide regime of magnetic fields. We find the LLs of phosphorene nanoribbon depend strongly on the ribbon orientation due to the anisotropic hopping parameters. The Hall and the longitudinal conductances (resistances) clearly reveal the structure of LLs.
Context:
The epidemiology of primary hyperparathyroidism (PHPT) has generally been studied in Caucasian populations.
Objective:
The aim was to examine the incidence and prevalence of PHPT within a ...racially mixed population.
Design:
A descriptive epidemiologic study was performed.
Patients/Setting:
The study population included 3.5 million enrollees within Kaiser Permanente Southern California.
Methods:
All patients with at least one elevated serum calcium level (>10.5 mg/dL, 2.6 mmol/L) between 1995 and 2010 were included. Cases of PHPT were identified by electronic query of laboratory values using biochemical criteria, after exclusion of secondary or renal and tertiary hyperparathyroidism cases. The incidence and prevalence rates of PHPT were calculated according to sex, race, age group by decade, and year.
Results:
Initial case finding identified 15,234 patients with chronic hypercalcemia, 13,327 (87%) of which had PHPT as defined by elevated or inappropriately normal parathyroid hormone levels. The incidence of PHPT fluctuated from 34 to 120 per 100 000 person-years (mean 66) among women, and from 13 to 36 (mean 25) among men. With advancing age, incidence increased and sex differences became pronounced (incidence 12–24 per 100 000 for both sexes younger than 50 y; 80 and 36 per 100 000 for women and men aged 50–59 y, respectively; and 196 and 95 for women and men aged 70–79 y, respectively). The incidence of PHPT was highest among blacks (92 women; 46 men, P < .0001), followed by whites (81 women; 29 men), with rates for Asians (52 women, 28 men), Hispanics (49 women, 17 men), and other races (25 women, 6 men) being lower than that for whites (P < .0001). The prevalence of PHPT tripled during the study period, increasing from 76 to 233 per 100 000 women and from 30 to 85 per 100 000 men. Racial differences in prevalence mirrored those found in incidence.
Conclusions:
PHPT is the predominant cause of hypercalcemia and is increasingly prevalent. Substantial differences are found in the incidence and prevalence of PHPT between races.
In present study, the Inconel 718 alloys fabricated by selective laser melting (SLM) were subjected to traditional homogenization plus double aging heat treatment (HT1), and a novel heat treatment ...(HT2). The effect of heat treatment on the anisotropic microstructure and the small punch creep (SPC) property of Inconel 718 samples was investigated. The experimental results show that the general high-angle grain boundaries with stress concentration, and the equiaxed and columnar grains are observed in the HT1 samples. Compared with the traditional solution treatment at 1065 °C for the HT1 samples, a higher solution performed at 1150 °C can efficiently eliminate the stress concentration and lead to the transformation of columnar grains to equiaxed grains in the HT2 samples by introducing complete recrystallization. The recrystallization is accompanied by the formation of annealing twins with high proportion Σ3n (n = 1, 2, 3) twin boundaries. The larger γ″ phases, less grain boundaries perpendicular to the load direction and smaller Laves phases in the HT1-Z (Z represents parallel to the building direction) sample result in a longer creep life. Microcracks distributed along the general high-angle grain boundaries rather than twin boundaries promote the final intergranular fracture. The anisotropy in creep rupture time of SLMed Inconel 718 alloy can be obviously alleviated by applying higher temperature solution treatment.
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