The Gut Microbiota and Alzheimer's Disease Jiang, Chunmei; Li, Guangning; Huang, Pengru ...
Journal of Alzheimer's disease,
01/2017, Letnik:
58, Številka:
1
Journal Article
Recenzirano
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also ...central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.
Quantum cascade lasers are highly stable against optical feedback, where the reflection mirror is well aligned with the optical path. Therefore, it is challenging to produce pulse oscillations in ...quantum cascade lasers through normal optical feedback. In this work, we show that tilted optical feedback with a misaligned reflection mirror triggers quantum cascade lasers to generate low-frequency oscillations, including irregular pulse oscillations and square wave oscillations. The oscillation period is in the microsecond range, and generally decreases with increasing tilt angle. In addition, the duty cycle of the square waves is tunable through varying the tilt angle. It is also found that a weak feedback strength or a low pump current yields rare occurrence of the pulse oscillations.
Two decades of studies in multiple model organisms have established the Hippo pathway as a key regulator of organ size and tissue homeostasis. By inhibiting YAP and TAZ transcription co-activators, ...the Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status. Dysregulation of the Hippo pathway exerts a significant impact on cancer development. Further investigation of the functions and regulatory mechanisms of this pathway will help uncovering the mystery of organ size control and identify new targets for cancer treatment.
In response to a variety of cellular signals, the Hippo pathway plays key roles in regulating tissue homeostasis, stemness, and cancer development.
We dissect the enabling capabilities of the tunable period-one (P1) limit cycles of optically injected quantum cascade laser (QCL) oscillators for the generation of optical frequency combs. As such, ...we theoretically investigate the P1 dynamics of a QCL using a single-mode rate equation model. We find that such a P1 limit cycle occupies a rather large and wide region of the optical frequency detuning and injection level ratio map. We have not recorded evidence of chaos in this injected laser system, in marked contrast with quantum well and quantum dot cases. Contrary to interband semiconductor lasers, the QCL's oscillation frequency is generally smaller than the detuning frequency, and is reduced with increasing injection strength, due to the strong injection pulling effect. When the optical injection is operated in the vicinity of the Hopf bifurcation, the P1 oscillation produces dense optical frequency combs, owing to both the frequency pulling effect and the four-wave mixing effect. The comb spacing is continuously tunable from subgigahertz up to a few gigahertz, via fine control of either the detuning frequency and/or the injection ratio. This novel approach of the frequency comb generation is of prime importance for high-resolution detection of narrow absorption lines of gas molecules.
Surface plasmon resonances (SPRs) have been found to promote chemical reactions. In most oxidative chemical reactions oxygen molecules participate and understanding of the activation mechanism of ...oxygen molecules is highly important. For this purpose, we applied surface‐enhanced Raman spectroscopy (SERS) to find out the mechanism of SPR‐assisted activation of oxygen, by using p‐aminothiophenol (PATP), which undergoes a SPR‐assisted selective oxidation, as a probe molecule. In this way, SPR has the dual function of activating the chemical reaction and enhancing the Raman signal of surface species. Both experiments and DFT calculations reveal that oxygen molecules were activated by accepting an electron from a metal nanoparticle under the excitation of SPR to form a strongly adsorbed oxygen molecule anion. The anion was then transformed to Au or Ag oxides or hydroxides on the surface to oxidize the surface species, which was also supported by the heating effect of the SPR. This work points to a promising new era of SPR‐assisted catalytic reactions.
Plasmon‐assisted reactions: Surface plasmon resonances (SPRs) support the activation of oxygen to yield metallic oxides and hydroxides on surfaces of Au and Ag nanoparticles, which selectively oxidize molecular species on the surface by laser light illumination. The electron donation to oxygen as well as a local heating effect in the presence of SPRs account for the activation of oxygen.
High-performance solar-blind (200–280 nm) avalanche photodetectors (APDs) were fabricated based on highly crystallized ZnO–Ga2O3 core–shell microwires. The responsivity can reach up to 1.3 × 103 A/W ...under −6 V bias. Moreover, the corresponding detectivity was as high as 9.91 × 1014 cm·Hz1/2/W. The device also showed a fast response, with a rise time shorter than 20 μs and a decay time of 42 μs. The quality of the detectors in solar-blind waveband is comparable to or even higher than that of commercial Si APD (APD120A2 from Thorlabs Inc.), with a responsivity ∼8 A/W, detectivity ∼1012 cm·Hz1/2/W, and response time ∼20 ns. The high performance of this APD make it highly suitable for practical applications as solar-blind photodetectors, and this core–shell microstructure heterojunction design method would provide a new approach for realizing an APD device.
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•The output data and potential of industrial solid wastes for CO2 mineralization are analyzed.•The limitation reasons of CO2 mineralization for industrial applications are found.•The ...huge energy and cost consumption is the biggest block for its progress.•The approaches for reducing energy and cost consumption are reviewed.
CO2 mineral carbonation is a promising strategy to abate global warming. However, its industrial applications were still limited. This paper reviews the current developments of mineral carbonation technologies by using industrial solid wastes as feedstocks, aiming at searching the reasons of its limitation. Firstly, the pathways and principles for CO2 mineral carbonation are briefly introduced. Then, the carbonation potential and processes of the most representative and available industrial solid wastes are summarized and compared. Iron and steel slags exhibit great potential due to their high alkali content and reactivity. Based on the preliminary economic analysis, the reasons for the limitation of current scale-up applications of CO2 mineral carbonation are the concerns of energy and cost consumption. The process parameter optimization and equipment design for scale-up applications need to be extensively investigated. Meanwhile, the recovery of high-value products during the carbonation process improves the economy and make the process more promising for industrial applications. The feasibility for recovering various value-added byproducts such as precipitated calcium carbonate (PCC) and zeolites was reported and discussed in this paper. Lastly, two research directions, i.e. the evaluation of CO2 net emission reduction by life cycle assessment technique and developments of new energy-saving approaches, are suggested.
Thanks to the advantages of high power density and the capacity of bidirectional power transfer, the CLLC resonant converter is widely used in the hybrid ac-dc microgrid as a dc transformer to ...interlink the ac and dc bus. Since the voltages of ac and dc bus are controlled by the energy management system, the CLLC resonant converter operates under open-loop condition, which means the switching frequency and duty cycle are fixed. As a result, in the hybrid ac-dc microgrid applications, for the CLLC converter, the main concern is not the voltage regulation but the conversion efficiency. This paper focuses on the total power loss optimization and the magnetic design of the CLLC resonant converter based on artificial intelligence (AI) algorithm. In order to optimize the total power loss, an AI algorithm-based two-stage optimal design method is proposed. In the first stage, the total power loss, including the driving loss, turn- off loss, conduction loss of the switches, the power loss of the resonant capacitances, and copper and core loss of the transformer are optimized by the proposed AI algorithm, GA+PSO, and the optimal parameters, including the leakage inductances ( L r 1 and L r 2 ), magnetizing inductance ( L m ), and resonant capacitances ( C r 1 and C r 2 ) are derived. In the second stage, the optimal leakage inductances and magnetizing inductance are realized by setting proper distance between the primary winding and the secondary winding ( d w ), and the thickness of the air gap ( d a ). As for the magnetic design, in this paper, the leakage inductances of a planar transformer are used as the resonant inductances. The equations of d w and d a to achieve the optimal leakage inductances and magnetizing inductance are derived. Both the proposed optimal design method and the equations of d w and d a are validated by simulations and experiments.
Following an extensive review of the literature, we further analyze the published data to examine the health effects of indoor exposure to particulate matter (PM) of outdoor origin. We obtained data ...on all-cause, cardiovascular, and respiratory mortality per 10 μg/m3 increase in outdoor PM10 or PM2.5; the infiltration factors for buildings; and estimated time spent outdoors by individuals in the United States, Europe, China, and globally. These data were combined log-linear exposure-response model to estimate the all-cause, cardiovascular, and respiratory mortality of exposure to indoor PM pollution of outdoor origin. Indoor PM pollution of outdoor origin is a cause of considerable mortality, accounting for 81% to 89% of the total increase in mortality associated with exposure to outdoor PM pollution for the studied regions. The findings suggest that enhancing the capacity of buildings to protect occupants against exposure to outdoor PM pollution has significant potential to improve public health outcomes.
Background:
Inhibitors targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have unprecedented effects in cancer treatment. However, the objective response rates (ORRs), ...progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 blockade monotherapy have not been systematically evaluated.
Methods:
We searched Embase, PubMed, and Cochrane database from inception to July 2019 for prospective clinical trials on single-agent PD-1/PD-L1 antibodies (avelumab, atezolizumab, durvalumab, cemiplimab, pembrolizumab, and nivolumab) with information regarding ORR, PFS, and OS.
Results:
Totally, 28,304 patients from 160 perspective trials were included. Overall, 4747 responses occurred in 22,165 patients treated with PD-1/PD-L1 monotherapy ORR, 20.21%; 95% confidence interval (CI), 18.34–22.15%. Compared with conventional therapy, PD-1/PD-L1 blockade immunotherapy was associated with more tumor responses (odds ratio, 1.98; 95% CI, 1.52–2.57) and better OS hazard ratio (HR), 0.75; 95% CI, 0.67–0.83. The ORRs varied significantly across cancer types and PD-L1 expression status. Line of treatment, clinical phase and drug target also impacted the response rates in some tumors. A total of 2313 of 9494 PD-L1 positive patients (ORR, 24.39%; 95% CI, 22.29–26.54%) and 456 of 4215 PD-L1 negative patients (ORR, 10.34%; 95% CI, 8.67–12.14%) achieved responses. For PD-L1 negative patients, the ORR (odds ratio, 0.92; 95% CI, 0.70–1.20) and PFS (HR, 1.15; 95% CI, 0.87–1.51) associated with immunotherapy and conventional treatment were similar. However, PD-1/PD-L1 blockade monotherapy decreased the risk of death in both PD-L1 positive (HR, 0.66; 95% CI, 0.60–0.72) and PD-L1 negative (HR, 0.86; 95% CI, 0.74–0.99) patients compared with conventional therapy.
Conclusion:
The efficacies associated with PD-1/PD-L1 monotherapy vary significantly across cancer types and PD-L1 expression. This comprehensive summary of clinical benefit from immunotherapy in cancer patients provides an important guide for clinicians.
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