Indoles from commensal bacteria extend healthspan Sonowal, Robert; Swimm, Alyson; Sahoo, Anusmita ...
Proceedings of the National Academy of Sciences - PNAS,
09/2017, Volume:
114, Issue:
36
Journal Article
Peer reviewed
Open access
Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant ...extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.
Abstract
Imbalanced Alfvénic turbulence is a universal process playing a crucial role in energy transfer in space, astrophysical, and laboratory plasmas. A fundamental and long-lasting question ...about the imbalanced Alfvénic turbulence is how and through which mechanism the energy transfers between scales. Here, we show that the energy transfer of imbalanced Alfvénic turbulence is completed by coherent interactions between Alfvén waves and co-propagating anomalous fluctuations. These anomalous fluctuations are generated by nonlinear couplings instead of linear reflection. We also reveal that the energy transfer of the waves and the anomalous fluctuations is carried out mainly through local-scale and large-scale nonlinear interactions, respectively, responsible for their bifurcated power-law spectra. This work unveils the energy transfer physics of imbalanced Alfvénic turbulence, and advances the understanding of imbalanced Alfvénic turbulence observed by Parker Solar Probe in the inner heliosphere.
Abstract
Nanosized metals usually exhibit ultrahigh strength but suffer from low homogeneous plasticity. The origin of a strength–ductility trade-off has been well studied for pure metals, but not ...for random solid solution (RSS) alloys. How RSS alloys accommodate plasticity and whether they can achieve synergy between high strength and superplasticity has remained unresolved. Here, we show that face-centered cubic (FCC) RSS AuCu alloy nanowires (NWs) exhibit superplasticity of ~260% and ultrahigh strength of ~6 GPa, overcoming the trade-off between strength and ductility. These excellent properties originate from profuse hexagonal close-packed (HCP) phase generation (2H and 4H phases), recurrence of reversible FCC-HCP phase transition, and zigzag-like nanotwin generation, which has rarely been reported before. Such a mechanism stems from the inherent chemical inhomogeneity, which leads to widely distributed and overlapping energy barriers for the concurrent activation of multiple plasticity mechanisms. This naturally implies a similar deformation behavior for other highly concentrated solid-solution alloys with multiple principal elements, such as high/medium-entropy alloys. Our findings shed light on the effect of chemical inhomogeneity on the plastic deformation mechanism of solid-solution alloys.
Abstract
Plasma energization and thermalization in magnetic reconnection is an important topic in astrophysical studies. We select two magnetic reconnection exhausts encountered by Solar Orbiter and ...analyze the associated ion heating in the kinetic regime. Both cases feature asymmetric plasma merging in the exhaust and anisotropic heating. For a quantitative investigation of the associated complex velocity-space structures, we adopt a three-dimensional Hermite representation of the proton velocity distribution function to produce the distribution of Hermite moments. We also derive the enstrophy and Hermite spectra to analyze the free energy conversion and transfer in phase space. We find a depletion of Hermite power at small
m
(corresponding to large-scale structures in velocity space) inside the reconnection exhaust region, concurrent with enhanced proton temperature and decreased enstrophy. Furthermore, the slopes of the 1D time-averaged parallel Hermite spectra are lower inside the exhaust and consistent with the effect of phase mixing that creates small fluctuations in velocity space. These fluctuations store free energy at higher
m
and are smoothed by weak collisionality, leading to irreversible thermalization. We also suggest that the perpendicular heating may happen via perpendicular phase mixing resulting from finite Larmor radius effects around the exhaust boundary.
Oral cancers refer to malignant tumors associated with high morbidity and mortality, and oral squamous cell carcinoma accounts for the majority of cases. It is an important part of head and neck, and ...oral cancer is one of the six most common cancers in the world. At present, the traditional treatment methods for oral cancer include surgery, radiation therapy, and chemotherapy. However, these methods have many disadvantages. In recent years, nanomedicine, the delivery of drugs through nanoplatforms for the treatment of cancer, has become a promising substitutive therapy. The use of nanoplatforms can reduce the degradation of the drug in the body and accurately deliver it to the tumor site. This minimizes the distribution of the drug to other organs, thereby reducing its toxicity and allowing higher drug concentration at the tumor site. This review introduces polymer nanoparticles, lipid-based nanoparticles, metal nanoparticles, hydrogels, exosomes, and dendrimers for the treatment of oral cancer, and discusses how these nanoplatforms play an anti-cancer effect. Finally, the review gives a slight outlook on the future prospects of nanoplatforms for oral cancer treatment.
Areal density gradient flyers (ADGFs) have important applications in quasi-isentropic compression and high strain rate loading. The wave impedance gradient distribution of the reported ADGFs is ...single, and the effects of different wave impedance gradient distributions and spikes number density on the loading results are unknown. In this study, the resin-based ADGFs with different spike areal density distribution and spikes number density were designed and prepared using projection micro stereolithography technology (PμSL). The printing accuracy of ADGFs was evaluated using three-dimensional optical profiler, optical microscope, Scanning Electron Microscopy (SEM) and ultra depth of field microscope. The loading process of the ADGF on the target was studied by experiment and simulation. The simulation result was consistent with the experimental result. Augmenting the wave impedance distribution index (P) of spikes and spikes number density increases the loading strain rate. Due to the high printing accuracy of PμSL, the fine ADGF structures with large spikes number density can be prepared, thereby promoting the formation of quasi-isentropic compression plane waves. This work realizes the regulation of loading strain rate under shockless quasi-isentropic compression, which is significant for understanding the mechanical response of materials under high strain rate loads.
•The different growth modes of wave impedance gradient are formed by the design of geometric structure.•The regulation of the loading strain rate within 104 s−1 is realized by changing the growth mode of the wave impedance gradient and the number density of the spikes.•Construction of the flyer's fine structure accelerates the transition from chaotic loading to uniaxial loading in the target.
Abstract
The acceleration and heating of solar wind particles by magnetic reconnection are important mechanisms in space physics. Although alpha particles (
4
He
2+
) are the second most abundant ...population of solar wind ions, their kinetic behavior in solar wind magnetic reconnection is not well understood. Using the high-energy (1500–3000 eV) range of the Solar Wind Analyser/Proton–Alpha Sensor instrument on board Solar Orbiter, we study the kinetic features of alpha particles in an exhaust region of a Pestchek-like solar-wind reconnection event with a weak guide field. A pair of back-to-back compound discontinuities is observed in the exhaust region. We find that the plasma in the magnetic exhaust region is heated and bounded by slow shocks (SSs), while the accelerated reconnection jet is bounded by rotational discontinuities (RDs). The SSs are outside the RDs, which is not expected from the magnetohydrodynamical prediction. We suggest this different location of the discontinuities is due to the enhanced parallel temperature
T
p
∥
>
T
p
⊥
, which reduces the local Alfvén speed in the exhaust region, allowing the SSs to propagate faster than the RDs. Inside the exhaust region, the guide field is dominant. We find a two-population distribution of the alpha particles. These two populations are field aligned downstream the SSs and shift to have a perpendicular offset in the reconnection jet, suggesting that the change of the magnetic field at the RDs has similar timescales with the proton gyroperiod, but faster than those of the alpha particles, such that the alpha particles behave like pickup ions.
When solving the problem of the minimum cost consensus with asymmetric adjustment costs, decision makers need to face various uncertain situations (such as individual opinions and unit adjustment ...costs for opinion modifications in the up and down directions). However, in the existing methods for dealing with this problem, robust optimization will lead to overly conservative results, and stochastic programming needs to know the exact probability distribution. In order to overcome these shortcomings, it is essential to develop a novelty consensus model. Thus, we propose three new minimum-cost consensus models with a distributionally robust method. Uncertain parameters (individual opinions, unit adjustment costs for opinion modifications in the up and down directions, the degree of tolerance, and the range of thresholds) were investigated by modeling the three new models, respectively. In the distributionally robust method, the construction of an ambiguous set is very important. Based on the historical data information, we chose the Wasserstein ambiguous set with the Wasserstein distance in this study. Then, three new models were transformed into a second-order cone programming problem to simplify the calculations. Further, a case from the EU Trade and Animal Welfare (TAW) program policy consultation was used to verify the practicability of the proposed models. Through comparison and sensitivity analysis, the numerical results showed that the three new models fit the complex decision environment better.
Bacterial infection refers to the process in which bacteria invade, grow, reproduce, and interact with the body, ultimately causing a series of pathological changes. Nowadays, bacterial infection ...remains a significant public health issue, posing a huge threat to human health and a serious financial burden. In the post-antibiotic era, traditional antibiotics are prone to inducing bacterial resistance and difficulty in removing bacterial biofilm. In recent years, antibacterial therapy based on nanomaterials has developed rapidly. Compared with traditional antibiotics, nanomaterials effectively remove bacterial biofilms and rarely result in bacterial resistance. However, due to nanomaterials’ strong permeability and effectiveness, they will easily cause cytotoxicity when they are not controlled. In addition, the antibacterial effect of non-responsive nanomaterials cannot be perfectly exerted since the drug release property or other antibacterial effects of these nano-materials are not be positively correlated with the intensity of bacterial infection. Stimuli-responsive antibacterial nanomaterials are a more advanced and intelligent class of nano drugs, which are controlled by exogenous stimuli and microenvironmental stimuli to change the dosage and intensity of treatment. The excellent spatiotemporal controllability enables stimuli-responsive nanomaterials to treat bacterial infections precisely. In this review, we first elaborate on the design principles of various stimuli-responsive antibacterial nanomaterials. Then, we analyze and summarizes the antibacterial properties, advantages and shortcomings of different applied anti-bacterial strategies based on stimuli-responsive nanomaterials. Finally, we propose the challenges of employing stimuli-responsive nanomaterials and corresponding potential solutions.
The distinct climatic and geographical conditions make high‐altitude permafrost on the Tibetan Plateau suffer more severe degradation than polar permafrost. However, the microbial responses ...associated with greenhouse gas production in thawing permafrost remain obscured. Here we applied nanopore‐based long‐read metagenomics and high‐throughput RNA‐seq to explore microbial functional activities within the freeze‐thaw cycle in the active layers of permafrost at the Qilian Mountain. A bioinformatic framework was established to facilitate phylogenetic and functional annotation of the unassembled nanopore metagenome. By deploying this strategy, 42% more genera could be detected and 58% more genes were annotated to nitrogen and methane cycle. With the aid of such enlarged resolution, we observed vigorous aerobic methane oxidation by Methylomonas, which could serve as a bio‐filter to mitigate CH4 emissions from permafrost. Such filtering effect could be further consolidated by both on‐site gas phase measurement and incubation experiment that CO2 was the major form of carbon released from permafrost. Despite the increased transcriptional activities of aceticlastic methanogenesis pathways in the thawed permafrost active layer, CH4 generated during the thawing process could be effectively consumed by the microbiome. Additionally, the nitrogen metabolism in permafrost tends to be a closed cycle and active N2O consumption by the topsoil community was detected in the near‐surface gas phase. Our findings reveal that although the increased thawed state facilitated the heterotrophic nitrogen and methane metabolism, effective microbial methane oxidation in the active layer could serve as a bio‐filter to relieve the overall warming potentials of greenhouse gas emitted from thawed permafrost.
On‐site MinION metagenomics and RNA‐seq were combined to explore microbial functionalities of active layers of the soil of Qilian Mountain permafrost. With the developed annotation pipeline‐FUNpore, 42% more genera and 58% more genes were detected. Active methane consumption by Methylomonas could serve as a biofilter to mitigate CH4 emission from permafrost. Dissimilatory nitrate reduction to ammonia pathway enabled a closed microbial nitrogen cycle and N2O consumption was observed.
Highlights
On‐site MinION metagenomics and RNA‐seq were combined to explore microbial functionalities of active layers of the soil of Qilian Mountain permafrost.
With the developed annotation pipeline‐FUNpore, 42% more genera and 58% more genes were detected.
Active methane consumption by Methylomonas could serve as a biofilter to mitigate CH4 emission from permafrost.
Dissimilatory nitrate reduction to ammonia pathway enabled a closed microbial nitrogen cycle and N2O consumption was observed.
PDF
