Alzheimer's disease (AD) is a neurodegenerative brain disease and is the most common form of dementia. In recent years, many studies indicated the association of gut microbiota changes with metabolic ...diseases. However, the gut microbiota of AD has not been investigated. The present study aims to compare the gut microbiota in APP/PS1 transgenic mice of AD and C57/Bl6 wild-type (WT) mice by pyrosequencing the V3 and V4 regions of the bacterial 16S ribosomal RNA genes. The 3-, 6-, and 8-month-old APP/PS1 and WT mice were used to explore the effects of age on the gut microbiota. First, the results indicated that impaired spatial learning and memory appeared in 6-month-old APP/PS1 mice and was further aggravated in the 8-month-old group, which was consistent with immunohistochemical studies of amyloid plaque. Second, AD histological and behavioral manifestations in the APP/PS1 mice were found to be correlated with a specific gut microbiome state. Third, the microbiota diversity of APP/PS1 mice decreased with increased age. Fourth, further inspection showed that the abundance of Helicobacteraceae and Desulfovibrionaceae at the family level and Odoribacter and Helicobacter at the genus level increased significantly in APP/PS1 mice than in WT mice, while Prevotella abundance in WT mice was significantly higher than in APP/PS1 mice. More human studies are warranted to explore the potential of gut microbiota as diagnostic biomarkers or therapeutic target for AD.
Compared with thin‐film morphology, 1D perovskite structures such as micro/nanowires with fewer grain boundaries and lower defect density are very suitable for high‐performance photodetectors with ...higher stability. Although the stability of perovskite microwire‐based photodetectors has been substantially enhanced in comparison with that of photodetectors based on thin‐film morphology, practical applications require further improvements to the stability before implementation. In this study, a template‐assisted method is developed to prepare methylammonium lead bromide (MAPbBr3) micro/nanowire structures, which are encapsulated in situ by a protective hydrophobic molecular layer. The combination of the protective layer, high crystalline quality, and highly ordered microstructures significantly improve the stability of the MAPbBr3 single‐crystal microwire arrays. Consequently, these MAPbBr3 single‐crystal microwire‐array‐based photodetectors exhibit significant long‐term stability, maintaining 96% of the initial photocurrent after 1 year without further encapsulation. The lifetime of such photodetectors is hence approximately four times longer than that of the most stable previously reported perovskite micro/nanowire‐based photodetector; this is thought to be the most stable perovskite photodetector reported thus far. Furthermore, this work should contribute further toward the realization of perovskite 1D structures with long‐term stability.
MAPbBr3 single‐crystal microwire arrays with designable shape, controllable size, and high crystalline quality are fabricated. The combination of the hydrophobic molecular protective layer, high crystalline quality, and highly ordered microstructures, improve the intrinsic stability of MAPbBr3 single‐crystal microwire arrays. Thus, a flexible photodetector with long‐term performance stability of more than 1 year is achieved.
Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and ...how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR‐103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR‐103‐expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR‐103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR‐103‐expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR‐103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR‐103‐expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR‐103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell‐secreted miR‐103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE‐Cadherin (VE‐Cad), p120‐catenin (p120) and zonula occludens 1. Moreover, miR‐103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells. Conclusion: Hepatoma cell‐secreted exosomal miR‐103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR‐103 as a potential therapeutic target and a predictive marker for HCC metastasis. (Hepatology 2018).
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified ...insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle‐aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non‐pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.
Wide bandgap (WB) organic–inorganic hybrid perovskites (OIHPs) with a bandgap ranging between 1.7 and 2.0 eV have shown great potential to improve the efficiency of single‐junction silicon or ...thin‐film solar cells by forming a tandem structure with one of these cells or with a narrow bandgap perovskite cell. However, WB‐OIHPs suffer from a large open‐circuit voltage (Voc) deficit in photovoltaic devices, which is associated with the phase segregation of the materials under light illumination. In this work the photoinstability is demonstrated and Voc loss can be addressed by combining grain crystallization and grain boundary passivation, achieved simultaneously through tuning of perovskite precursor composition. Using FA0.17Cs0.83PbI3–xBrx (x = 0.8, 1.2 1.5, and 1.8), with a varied bandgap from 1.72 to 1.93 eV, as the model system it is illustrated how precursor additive Pb(SCN)2 should be matched with a proper ratio of FAX (I and Br) to realize large grains with defect‐healed grain boundaries. The optimized WB‐OIHPs show good photostability at both room‐temperature and elevated temperature. Moreover, the corresponding solar cells exhibit excellent photovoltaic performances with the champion Voc/stabilized power output efficiency reaching 1.244 V/18.60%, 1.284 V/16.51%, 1.296 V/15.01%, and 1.312 V/14.35% for WB‐OIHPs with x = 0.8, 1.2, 1.5, and 1.8, respectively.
The photoinduced phase segregation in wide bandgap hybrid perovskites are greatly suppressed by combining grain crystallization and grain boundary passivation. As a result, the open‐circuit voltage (Voc) loss of the corresponding devices is highly reduced, demonstrating a monotonic increase of Voc with increasing of bandgap from 1.72 to 1.93 eV.
A long-lived hot carrier population is critical in order to develop working hot carrier photovoltaic devices with efficiencies exceeding the Shockley-Queisser limit. Here, we report photoluminescence ...from hot-carriers with unexpectedly long lifetime (a few ns) in formamidinium tin triiodide. An unusual large blue shift of the time-integrated photoluminescence with increasing excitation power (150 meV at 24 K and 75 meV at 293 K) is displayed. On the basis of the analysis of energy-resolved and time-resolved photoluminescence, we posit that these phenomena are associated with slow hot carrier relaxation and state-filling of band edge states. These observations are both important for our understanding of lead-free hybrid perovskites and for an eventual future development of efficient lead-free perovskite photovoltaics.
Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly ...diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.
Enjoying great safety, high power, and high energy densities, all-solid-state batteries play a key role in the next generation energy storage devices. However, their development is limited by the ...lack of solid electrolyte materials that can reach the practically useful conductivities of 10−2 S/cm at room temperature (RT). Here, by exploring a set of lithium-rich antiperovskites composed of cluster ions, we report a lithium superionic conductor, Li₃SBF₄, that has an estimated 3D RT conductivity of 10−2 S/cm, a low activation energy of 0.210 eV, a giant band gap of 8.5 eV, a small formation energy, a high melting point, and desired mechanical properties. A mixed phase of the material, Li₃S(BF₄)0.5Cl0.5, with the same simple crystal structure exhibits an RT conductivity as high as 10−1 S/cm and a low activation energy of 0.176 eV. The high ionic conductivity of the crystals is enabled by the thermal-excited vibrational modes of the cluster ions and the large channel size created by mixing the large cluster ion with the small elementary ion.
Benzylamine is introduced as a surface passivation molecule that improves the moisture‐resistance of the perovskites while simultaneously enhancing their electronic properties. Solar cells based on ...benzylamine‐modified formamidinium lead iodide perovskite films exhibit a champion efficiency of 19.2% and an open‐circuit voltage of 1.12 V. The modified FAPbI3 films exhibit no degradation after >2800 h air exposure.
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