Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus ...possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.
Nucleotide-binding, leucine-rich repeat receptors (NLRs) are major immune receptors in plants and animals. Upon activation, the Arabidopsis NLR protein ZAR1 forms a pentameric resistosome in vitro ...and triggers immune responses and cell death in plants. In this study, we employed single-molecule imaging to show that the activated ZAR1 protein can form pentameric complexes in the plasma membrane. The ZAR1 resistosome displayed ion channel activity in Xenopus oocytes in a manner dependent on a conserved acidic residue Glu11 situated in the channel pore. Pre-assembled ZAR1 resistosome was readily incorporated into planar lipid-bilayers and displayed calcium-permeable cation-selective channel activity. Furthermore, we show that activation of ZAR1 in the plant cell led to Glu11-dependent Ca2+ influx, perturbation of subcellular structures, production of reactive oxygen species, and cell death. The results thus support that the ZAR1 resistosome acts as a calcium-permeable cation channel to trigger immunity and cell death.
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•Resistosome formed by the immune receptor ZAR1 is a cation-selective channel•The ZAR1 channel is permeable to calcium•The activated ZAR1 forms a pentamer in the plasma membrane•The channel activity triggers immune signaling and cell death in plants
ZAR1 resistosome is a calcium-permeable channel that triggers immune signaling and cell death in plants.
Resistance to β‐lactam antibacterials is commonly associated with the production of the serine β‐lactamases (SBLs) and/or metallo‐β‐lactamases (MBLs). Although clinically useful inhibitors for the ...SBLs have been developed, no equivalent inhibitors are available for the MBLs, which can hydrolyze almost all β‐lactam antibiotics, including the so‐called “last resort” carbapenems. It is still a challenging task to develop a clinically useful inhibitor that should be broad‐spectrum targeting multiple clinically relevant MBL enzymes that differ in their active site features. This review provides a detailed description of interaction modes of substrates and small‐molecule inhibitors with various MBL enzymes and highlights the importance of metal‐ and “anchor residue”‐binding features to achieve broad‐spectrum MBL inhibition. Recently emerging active site interference strategies include metal ion deprivation, metal ion replacement, and cysteine modification as challenging, but worth experimenting directions for inhibitor development. The metalloenzyme selectivity, metal‐binding pharmacophore, and cellular permeability and accumulation should be properly considered in the further development of clinically useful inhibitors to combat MBL‐mediated antibacterial resistance.
A facile strategy for the preparation of a nanoconfined Ti3C2/Ru cocatalyst by direct reduction of Ru3+ ions without an additional reductant was developed. The in situ formation of TiO2 nanosheets on ...the Ti3C2/Ru surface ensures the separation of the semiconductor and cocatalyst (TiO2–Ti3C2/Ru), resulting in charge segregation and migration more effective than those achieved by traditionally prepared Ru–TiO2–Ti3C2. Owing to its low Fermi level, the self-assembled Ti3C2/Ru cocatalyst accepted the photogenerated electrons and promoted H2 evolution without an induction period, while exhibiting high surface structure stability. The changes in the work function and surface terminations of Ti3C2 during the photocatalysis were revealed by DFT calculations and in situ diffuse reflectance infrared Fourier transform spectroscopy. The efficient electron transfer enabled by the structurally separated Ti3C2/Ru-based photocatalyst significantly reduced the electron–hole recombination, increasing the photocatalytic H2 evolution activity. This work provides a guiding design approach for future solar energy conversion with the semiconductor–cocatalyst system.
With the climate constantly changing, plants suffer more frequently from various abiotic and biotic stresses. However, they have evolved biosynthetic machinery to survive in stressful environmental ...conditions. Flavonoids are involved in a variety of biological activities in plants, which can protect plants from different biotic (plant-parasitic nematodes, fungi and bacteria) and abiotic stresses (salt stress, drought stress, UV, higher and lower temperatures). Flavonoids contain several subgroups, including anthocyanidins, flavonols, flavones, flavanols, flavanones, chalcones, dihydrochalcones and dihydroflavonols, which are widely distributed in various plants. As the pathway of flavonoid biosynthesis has been well studied, many researchers have applied transgenic technologies in order to explore the molecular mechanism of genes associated with flavonoid biosynthesis; as such, many transgenic plants have shown a higher stress tolerance through the regulation of flavonoid content. In the present review, the classification, molecular structure and biological biosynthesis of flavonoids were summarized, and the roles of flavonoids under various forms of biotic and abiotic stress in plants were also included. In addition, the effect of applying genes associated with flavonoid biosynthesis on the enhancement of plant tolerance under various biotic and abiotic stresses was also discussed.
Synthetic lethality is the synthesis of mutations leading to cell death. Tumor‐specific synthetic lethality has been targeted in research to improve cancer therapy. With the advances of techniques in ...molecular biology, such as RNAi and CRISPR/Cas9 gene editing, efforts have been made to systematically identify synthetic lethal interactions, especially for frequently mutated genes in cancers. However, elucidating the mechanism of synthetic lethality remains a challenge because of the complexity of its influencing conditions. In this study, we proposed a new computational method to identify critical functional features that can accurately predict synthetic lethal interactions. This method incorporates several machine learning algorithms and encodes protein‐coding genes by an enrichment system derived from gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways to represent their functional features. We built a random forest‐based prediction engine by using 2120 selected features and obtained a Matthews correlation coefficient of 0.532. We examined the top 15 features and found that most of them have potential roles in synthetic lethality according to previous studies. These results demonstrate the ability of our proposed method to predict synthetic lethal interactions and provide a basis for further characterization of these particular genetic combinations.
A computational analysis of synthetic lethality was performed in this study. Synthetic lethality gene pairs were encoded via enrichment theory of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Advanced computational methods were adopted to build an optimal prediction model and extract important features.
Targeted saturation mutagenesis of crop genes could be applied to produce genetic variants with improved agronomic performance. However, tools for directed evolution of plant genes, such as ...error-prone PCR or DNA shuffling, are limited
. We engineered five saturated targeted endogenous mutagenesis editors (STEMEs) that can generate de novo mutations and facilitate directed evolution of plant genes. In rice protoplasts, STEME-1 edited cytosine and adenine at the same target site with C > T efficiency up to 61.61% and simultaneous C > T and A > G efficiency up to 15.10%. STEME-NG, which incorporates the nickase Cas9-NG protospacer-adjacent motif variant, was used with 20 individual single guide RNAs in rice protoplasts to produce near-saturated mutagenesis (73.21%) for a 56-amino-acid portion of the rice acetyl-coenzyme A carboxylase (OsACC). We also applied STEME-1 and STEME-NG for directed evolution of the OsACC gene in rice and obtained herbicide resistance mutations. This set of two STEMEs will accelerate trait development and should work in any plants amenable to CRISPR-based editing.
Background and Purpose
Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis ...through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota‐derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation.
Experimental Approach
AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP.
Key Results
Normobiotic FMT alleviated AP‐induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)‐associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP‐mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+‐dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti‐inflammatory activities in AP. Importantly, normobiotic FMT‐mediated NMN metabolism induced SIRT3–PRDX5 pathway activation during AP.
Conclusion and Implications
Gut microbiota‐derived NMN alleviates the severity of AP by activating the SIRT3–PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.
Sequence‐defined polymer is one of the most promising alternative media for high‐density data storage. It could be used to alleviate the problem of insufficient storage capacity of conventional ...silicon‐based devices for the explosively increasing data. To fulfil the goal of polymer data storage, suitable methods should be developed to accurately read and decode the information‐containing polymers, especially for those composed by a combination of the natural and unnatural monomers. Nanopore‐based approaches have become one of the most competitive analysis and sequencing techniques, which are expected to read both natural and synthetic polymers with single‐molecule precision and monomeric resolution. Herein, this work emphasizes the advances being made in nanopore reading and decoding of information stored in the man‐made polymers and DNA nanostructures, and discusses the challenges and opportunities towards the development and realization of high‐density data storage.
The emerging nanopore techniques have been validated as the promising low‐cost analytical and sequencing methods towards practical applications of high‐density polymer data storage. This concept discusses the nanopore‐based data storage systems based on polymer sequences and DNA nanostructures, and highlights the advances in nanopore processing and decoding of information stored in man‐made polymers containing unnatural monomer units.
Circular RNA in renal diseases Jin, Juan; Sun, Haolu; Shi, Chao ...
Journal of cellular and molecular medicine,
June 2020, Letnik:
24, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of ...evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.
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