There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating ...immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.
Abstract
We propose and study a toy model for the quantum measurements that yield the Born’s rule of quantum probability. In this model, the electrons interact with local photon modes and the photon ...modes are dissipatively coupled with local photon reservoirs. We treat the interactions of the electrons and photons with full quantum mechanical description, while the dissipative dynamics of the photon modes are treated via the Lindblad master equation. By assigning double quantum dots setup for the electrons coupling with local photons and photonic reservoirs, we show that the Born’s rule of quantum probability can emerge directly from microscopic quantum dynamics. We further discuss how the microscopic quantities such as the electron–photon coupling, detuning, and photon dissipation rate affect the quantum dynamics. Surprisingly, in the infinite long time measurement limit, the energy conservation already dictates the emergence of the Born’s rule of quantum probability. For finite-time measurement, the local photon dissipation rate determines the characteristic time-scale for the completion of the measurement, while other microscopic quantities affect the measurement dynamics. Therefore, in genuine measurements, the measured probability is determined by both the local devices and the quantum mechanical wavefunction.
Efficient approaches for intracellular delivery of nucleic acid reagents to achieve sensitive detection and regulation of gene and protein expressions are essential for chemistry and biology. We ...develop a novel electrostatic DNA nanoassembly that, for the first time, realizes hybridization chain reaction (HCR), a target-initiated alternating hybridization reaction between two hairpin probes, for signal amplification in living cells. The DNA nanoassembly has a designed structure with a core gold nanoparticle, a cationic peptide interlayer, and an electrostatically assembled outer layer of fluorophore-labeled hairpin DNA probes. It is shown to have high efficiency for cellular delivery of DNA probes via a unique endocytosis-independent mechanism that confers a significant advantage of overcoming endosomal entrapment. Moreover, electrostatic assembly of DNA probes enables target-initialized release of the probes from the nanoassembly via HCR. This intracellular HCR offers efficient signal amplification and enables ultrasensitive fluorescence activation imaging of mRNA expression with a picomolar detection limit. The results imply that the developed nanoassembly may provide an invaluable platform in low-abundance biomarker discovery and regulation for cell biology and theranostics.
Hydrogen is a green energy with the long-term sustainability and high energy density. Hydrogen evolution reaction via electrocatalysis is a prospective strategy for green hydrogen. Pt-based ...electrocatalysts have exhibited excellent electrocatalytic activities on hydrogen evolution reaction. But the scarce and costly Pt limits the application of hydrogen evolution reaction. Therefore, non-Pt/low-Pt electrocatalysts have attracted much research attention. Amorphous metal phosphide electrocatalysts have shown significant electrocatalytic activities on hydrogen evolution reaction for their special long-range disordered but short-/medium-range ordered structures with abundant active sites and adjustable electronic structures. Mechanisms and electrochemical parameters of hydrogen evolution reaction as well as characterization technologies and atomic configurations of amorphous metal phosphides are firstly illustrated in the review. Amorphous monometallic, bimetallic, trimetallic and other multimetallic phosphides were investigated for modulation of electronic structures and active sites by heteroatom incorporation, nanoporous structure and heterostructure construction. The electrocatalytic performances of these amorphous metal phosphides are summarized in the review. Whereas some questions have emerged in recent researches, like atom leaching, uncertain self-constructions and lack of atomic configurations. Therefore, the future perspectives for the development of amorphous metal phosphide electrocatalysts on hydrogen evolution reaction are construction of stable amorphous metal phosphide electrocatalysts, exploration of self-construction mechanism and convenient construction of atomic configurations.
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•Amorphous metal phosphides exhibit significant electrocatalytic activities on HER.•Abundant active sites and adjustable electron structures result in high activities.•Monometallic, bimetallic, trimetallic and multimetallic phosphides are summarized.•Heteroatom incorporation, nanopore and heterostructure construction are explored.•Questions and perspectives are proposed for the development of industrial HER.
•The glass forming ability of high entropy metallic glasses (HE-MGs) and strategies to fabricate high entropy bulk metallic glasses (HE-BMGs) has been reviewed and summarized.•The crystallization ...process and products of HE-MGs and HE-BMGs have been reviewed.•The mechanical properties of HE-BMGs have been reviewed.•The magnetic properties and related parameters have been summarized.
The metallic glasses (MGs) and high entropy alloys (HEAs) have drawn great attention due to their remarkable features such as high hardness, strength and elasticity in MGs, and significant tensile ductility in HEAs. These great merits are attributed to the disorder atomic arrangement in MGs or simple crystalline phases with the face centred cubic structure in HEAs. However, MGs and HEAs have been demonstrated to be brittle and low strength, respectively. To date, many attempts have devoted to resolve these pressing issues. For MGs, the concept of transformation-induced plasticity or heterogeneous atomic arrangement have been introduced to enhance ductility and to activate work-hardening while the enhancement of tensile strength in HEAs has been the hot subject. Recently, various deformation mechanisms have been proposed to enhance yield/fracture strength without sacrificing much tensile ductility. The high entropy metallic glasses (HE-MGs), combining the features of both metallic glasses and high entropy alloys, appeared recently and have become the focal point. Hence, to promote this new field, it is useful to summarize the recently progress of HE-MGs. This review briefly presents a summary of HE-MGs regarding on glass formation, magnetic properties, crystallization and mechanical properties.
Ever since the axial chiral catalysts were developed for asymmetric reactions with excellent chiral discrimination and high efficiencies, the interest in the supramolecular catalyst has also been ...extensively investigated. Here, with a hint from the typical molecular catalyst, we developed a series of metal-coordinated nanotube (M-helical nanotube, M-HN) catalysts for asymmetric reactions. The M-HN catalyst was fabricated on the basis of the self-assembly of an l-glutamic acid terminated bolaamphiphile, which formed a single-walled nanotube. On one hand, through the coordination of transition metal ions with the carboxylic acid groups on the nanotube surface, a wide variety of single-walled M-HN catalysts could be fabricated, in which the coordination sites could serve as the catalytic sites. On the other hand, using a slight amount of these catalysts, significant reactivity and enantioselectivity were realized for certain asymmetric reactions under mild conditions. Remarkably, Bi(III)-HN could catalyze the asymmetric Mukaiyama aldol reaction with high enantioselectivity (up to 97% ee) in an aqueous system; Cu(II)-HN catalyzed the asymmetric Diels–Alder reaction with up to 91% ee within 60 min. It was suggested that a synergetic effect of the aligned multicatalytic sites and stereochemical selectivity of the M-HN lead to an excellent catalytic performance. Through this work, we proposed a new concept of a single-walled nanotube as catalyst and showed the first example of nanotube catalysts presenting high reactivity and enantioselectivity that rivaled a chiral molecular catalyst.
Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and ...Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor-κB (NF-κB) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products.
Dysfunctional transcription factors that activate abnormal expressions of specific proteins are often associated with the progression of various diseases. Despite being attractive drug targets, the ...lack of druggable sites has dramatically hindered their drug development. The emergence of proteolysis targeting chimeras (PROTACs) has revitalized the drug development of many conventional hard‐to‐drug protein targets. Here, the use of a palindromic double‐strand DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF) is reported. The selective proteolysis of the dimerized phosphorylated receptor‐regulated Smad2/3 and inhibition of the canonical Smad pathway validates PASTE‐mediated PROTAF. Further aptamer‐guided active delivery of PASTE and near‐infrared light‐triggered PROTAF are demonstrated. Great potential in using PASTE for the selective degradation of the activated transcription factor is seen, providing a powerful tool for studying signaling pathways and developing precision medicines.
The canonical TGF‐β/Smad signaling pathway plays a central role in fibrogenesis. Abnormal activation of R‐Smad is reported to be tightly associated with the pathogenesis of fibrosis. Here, an NIR‐responsive palindromic DNA thalidomide conjugate (PASTE) has been developed for the selective proteolysis of activated phosphorylated R‐Smad, which leads to the inhibition of the canonical Smad pathway.
Light-up RNA aptamers are valuable tools for fluorescence imaging of RNA in living cells and thus for elucidating RNA functions and dynamics. However, no light-up RNA sensor has been reported for ...imaging of microRNAs (miRs) in mammalian cells. We report a novel genetically encoded RNA sensor for fluorescent imaging of miRs in living tumor cells using a light-up RNA aptamer that binds to sulforhodamine and separates it from a conjugated contact quencher. On the basis of the structural switching mechanism for molecular beacon, we show that the RNA sensor activates high-contrast fluorescence from the sulforhodamine-quencher conjugate when its stem–loop responsive motif hybridizes with target miR. The RNA sensor can be stably expressed within a designed tRNA scaffold in tumor cells and deliver light-up response to miR target. We also realize the RNA sensor for dual-emission, ratiometric imaging by coexpression of RNA sensor with GFP, enabling quantitative studies of target miR in living cells. Our design may provide a new paradigm for developing robust, sensitive light-up RNA sensors for RNA imaging applications.
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