High-dose radiation activates caspases in tumor cells to produce abundant DNA fragments for DNA sensing in antigen-presenting cells, but the intrinsic DNA sensing in tumor cells after radiation is ...rather limited. Here we demonstrate that irradiated tumor cells hijack caspase 9 signaling to suppress intrinsic DNA sensing. Instead of apoptotic genomic DNA, tumor-derived mitochondrial DNA triggers intrinsic DNA sensing. Specifically, loss of mitochondrial DNA sensing in Casp9
tumors abolishes the enhanced therapeutic effect of radiation. We demonstrated that combining emricasan, a pan-caspase inhibitor, with radiation generates synergistic therapeutic effects. Moreover, loss of CASP9 signaling in tumor cells led to adaptive resistance by upregulating programmed death-ligand 1 (PD-L1) and resulted in tumor relapse. Additional anti-PD-L1 blockade can further overcome this acquired immune resistance. Therefore, combining radiation with a caspase inhibitor and anti-PD-L1 can effectively control tumors by sequentially blocking both intrinsic and extrinsic inhibitory signaling.
Entorhinal cortex (EC), thought to be the location of the earliest lesions in Alzheimer’s disease (AD), has been widely studied in recent years. With the irreversible pathological changes of AD, ...there is an urgent need to find biomarkers that can be used to predict the presence of the disease before it is clinically expressed. The aim of this review is to summarize and analyze recent findings that are relevant to the important role of EC in the diagnosis of mild cognitive impairment (MCI) and mild AD and to describe a range of neuroimaging techniques used to define the EC boundary. A comprehensive literature search for articles published up to May 2015 was performed. Our research highlights the finding that atrophy in EC reflects the early pathological changes of AD and can be a strong predictor of prodromal AD. The early changes in EC are a good imaging biomarker that can be used to discriminate individuals with MCI from normal control subjects. A larger degree of atrophy in EC predicts increased disease severity, and the right EC in patients with mild AD exhibited greater changes than the left side. In addition, the EC seems to have an obvious advantage over the hippocampus as a biomarker when predicting future conversion to AD in individuals with MCI, and it may be of help in following the course of disease progression. In this review, we also summarize the main differences observed between the hippocampus and the EC when differentiating diseases. These findings will hopefully provide an opportunity for the effective prevention and early treatment of AD.
Being isolated from the peripheral system by the blood-brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) ...influences gastrointestinal and brain disorders such as Alzheimer's disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research.
The study aimed to explore the bacterial community composition and the functions of core microbiota in
Eucommia ulmoides
bark. The bark samples of
E. ulmoides
were collected from Wangcang Sichuan ...Province, Cili Hunan Province, and Zunyi Guizhou Province, in China, respectively. Through the high-throughput sequencing methods and techniques, the community composition, core microbiota, and function of the bacteria were studied. The bacterial community of
E. ulmoides
bark consisted of 9 phyla, 11 classes, 22 orders, 28 families, 31 genera, and 37 OTUs. At the genus level, the dominant genus was the unclassified bacteria of Cyanobacteria, with a relative abundance of 97.01%. The bacterial communities of
E. ulmoides
bark from different areas have their unique units except for the common microbiota. The core microbiota of bacteria included an unclassified genus of Cyanobacteria, an unclassified genus of Mitochondria,
Pseudomonas
,
Sphingobium
,
Rhizobium
,
Novosphingobium
,
Enterobacter
,
Rhodococcus
,
Curtobacterium,
and
Ralstonia
. FAPROTAX function prediction suggested that the core microbiota has a substantial potential for photoautotrophy, phototrophy, aerobic chemoheterotrophy, chemoheterotrophy. Ten taxa composed the core microbiota, and the majority of them were related to the pharmacologically active ingredients of
E. ulmoides
bark. The research provides a scientific basis for the biological marker of genuineness and microbial technology for improving the content of medicinal ingredients of
E. ulmoides
.
The family Thelebolaceae belongs to the order Thelebolales, class Leotiomycetes, and contains 22 genera. In this study, we introduce a new genus Solomyces gen. nov. in the family Thelebolaceae, which ...is supported by morphological observation and multilocus-based internal transcribed spacers (ITS) + LSU and ITS + LSU+ MCM7+ EF1A+ RPB2 phylogenetic analysis. Maximum-likelihood and Bayesian phylogenetic inference analyses indicated that Solomyces is a distinct genus within this family. The new genus is compared against related Thelebolaceae genera, and its description and illustration are provided. This genus comprises one new species and one unnamed species (including two strains). We also report the addition of four new species - Pseudogymnoascus shaanxiensis, Pseudogymnoascus guizhouensis, Pseudogymnoascus sinensis, and Geomyces obovatus - in the family Thelebolaceae and present their morphological and phylogenetic characterizations.
Medicinal plants are inhabited by diverse microbes in every compartment, and which play an essential role in host growth and development, nutrient absorption, synthesis of secondary metabolites, and ...resistance to biological and abiotic stress. However, the ecological processes that manage microbiota assembly and the phenotypic and metabolic characteristics of the core microbiota of
remain poorly explored. Here, we systematically evaluated the effects of genotypes, compartment niches, and environmental conditions (climate, soil nutrition, and secondary metabolites) on the assembly of rhizosphere soil and bark associated bacterial communities. In addition, phenotypic and metabolic characteristics of
core microbiota, and their relationship with dominant taxa, rare taxa, and pharmacologically active compounds were deciphered. Results suggested that microbiota assembly along the two compartments were predominantly shaped by the environment (especially pH, relative humidity, and geniposide acid) and not by host genotype or compartment niche. There were 690 shared genera in the rhizosphere soil and bark, and the bark microbiota was mainly derived from rhizosphere soil. Core microbiota of
was a highly interactive "hub" microbes connecting dominant and rare taxa, and its phenotypic characteristics had a selective effect on compartment niches. Metabolic functions of the core microbiota included ammonia oxidation, nitrogen fixation, and polyhydroxybutyrate storage, which are closely related to plant growth or metabolism. Moreover, some core taxa were also significantly correlated with three active compounds. These findings provide an important scientific basis for sustainable agricultural management based on the precise regulation of the rhizosphere soil and bark microbiota of
.
Members of the plant mycobiota are all associated to varying degrees with the development of plant diseases. Although many reports on the plant mycobiota are well documented, the relationships ...between mycobiota of
Rosa roxburghii
and plant diseases are poorly understood. Mutual interactions and extent of the roles of microbial communities associated with
R. roxburghii
and the source of pathogens are still unclear, and more research is needed on the health benefits of this ecologically important population. Using high-throughput sequencing, we analyzed the mycobiota composition and ecological guilds of the rhizosphere, root, and phyllosphere of healthy and diseased
R
.
roxburghii
from the Tianfu
R. roxburghii
Industrial Park in Panzhou city, Guizhou province. Analysis of community composition showed that the relative abundance of pathogens of leaf spot, including
Alternaria
,
Pestalotiopsis
and
Neofusicoccum
in the phyllosphere of diseased plant (LD), were 1.15%, 0.15% and 0.06%, and the relative abundance of
Alternaria
and
Pestalotiopsis
were 0.96% and 0.58% in healthy plant (LH). The alpha diversity indices indicated that fungal diversity was higher in healthy plants compared to diseased plants in each compartment. The alpha diversity index of fungi in the phyllosphere (LH) of healthy
R
.
roxburghii
, including Shannon, Chao-1, and Faith-pd indices, was 1.02, 81.50 and 10.42 higher than that of the diseased (LD), respectively. The fungi in the rhizosphere of healthy was 1.03, 59.00 and 5.56 higher than the diseased, respectively. The Shannon index of fungi in the root of healthy was 0.29 higher than that of diseased. Principal Coordinate analysis and ANOSIM results showed that there were significant differences in mycobiota composition between healthy and diseased phyllospheres (
P
< 0.05), as well as rhizosphere fungal community, while there was no significant difference between healthy and diseased roots (
P
> 0.05). Linear discriminant analysis effect size revealed that, at different taxonomic levels, there were significantly different taxa between the healthy and diseased plants in each compartment. The ecological guilds differed between healthy and diseased plants according to the FUNGuild analysis. For example, of healthy compared to diseased plants, the percentages of “lichenized-undefined saprotroph” were increased by 2.34%, 0.44%, and 1.54% in the phyllosphere, root, and rhizosphere, respectively. In addition, the plant pathogens existed in each compartment of
R
.
roxburghii
, but the percentages of “plant pathogen” were increased by 1.16% in the phyllosphere of diseased compared to healthy plants. Together, the ecological guild and co-occurrence network indicated that the potential pathogens of leaf spot were mainly found in the phyllosphere. This study explained one of pathogen origin of leaf spots of
R. roxburghii
by the microbial community ecology, which will provide the new insights for identification of plant pathogens.
Synthetic microbial community has widely concerned in the fields of agriculture, food and environment over the past few years. However, there is little consensus on the method to synthetic microbial ...community from construction to functional verification. Here, we review the concept, characteristics, history and applications of synthetic microbial community, summarizing several methods for synthetic microbial community construction, such as isolation culture, core microbiome mining, automated design, and gene editing. In addition, we also systematically summarized the design concepts, technological thresholds, and applicable scenarios of various construction methods, and highlighted their advantages and limitations. Ultimately, this review provides four efficient, detailed, easy-to-understand and -follow steps for synthetic microbial community construction, with major implications for agricultural practices, food production, and environmental governance.
DNA methylation is an epigenetic mechanism with the potential to regulate gene expression and affect plant phenotypes. Both hybridization and genome doubling may affect the DNA methylation status of ...newly formed allopolyploid plants. Previous studies demonstrated that changes in cytosine methylation levels and patterns were different among individual hybrid plant, therefore, studies investigating the characteristics of variation in cytosine methylation status must be conducted at the population level to avoid sampling error. In the present study, an F1 hybrid diploid population and three allotriploid populations with different heterozygosity originating from first-division restitution (FDR), second-division restitution (SDR), and post-meiotic restitution (PMR) 2n eggs of the same female parent were used to investigate cytosine methylation inheritance and variation relative to their common parents using methylation-sensitive amplification polymorphism (MSAP). The variation in cytosine methylation in individuals in each population exhibited substantial differences, confirming the necessity of population epigenetics. The total methylation levels of the diploid population were significantly higher than in the parents, but those of the three allotriploid populations were significantly lower than in the parents, indicating that both hybridization and polyploidization contributed to cytosine methylation variation. The vast majority of methylated status could be inherited from the parents, and the average percentages of non-additive variation were 6.29, 3.27, 5.49 and 5.07% in the diploid, FDR, SDR and PMR progeny populations, respectively. This study lays a foundation for further research on population epigenetics in allopolyploids.
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