We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and ...healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.
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•Feruloylated oligosaccharides and ferulic acid attenuated diabetic syndrome most likely by modulating the gut microbiota.•Feruloylated oligosaccharides and ferulic acid modulated the ...composition and metabolism of gut microbiome.•Feruloylated oligosaccharides showed regulative effects on gut microbiota which were different from ferulic acid.
Gut microbiome has been proven to be involved in the development of type 2 diabetes (T2D). Additionally, increasing evidence showed that the composition of gut microbiome is highly associated with the outcome of T2D therapy. Previously we demonstrated that feruloylated oligosaccharides (FOs) and ferulic acid (FA) alleviated diabetic syndrome in rats, but the detailed mechanism has not been explored yet. In this study we strived to characterize how FOs and FA altered the gut microbiome and related metabolome in diabetic rats by using high-throughput sequencing of 16S rRNA and gas chromatography (GC). Our results showed that FOs reduced the abundance of Lactobacillus, Ruminococcus, Oscillibacter, and Desulfovibrio, but increased the abundance of Akkermansia, Phascolarctobacterium and Turicibacter. The structure of gut microbiome in FOs treated rats was similar with healthy rats rather than diabetic rats. Likewise, FA decreased the portion of Lactobacillus, Ruminococcus, but promoted the growth of Bacteroides, Blautia, Faecalibacterium, Parabacteroides and Phascolarctobacterium. Additionally, the short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), the main bacterial lipid metabolites in gut mediating host glucose metabolism, was dramatically elevated along with FOs and FA treatment. Our findings indicated that FOs and FA attenuated diabetic syndrome in rats most likely by modulating the composition and metabolism of gut microbiome. The study gives new insight into the mechanism underlying the anti-diabetes effect of functional foods as well as facilitates the development of dietary supplements for diabetic patients.
In this work, we investigated the expression pattern and regulatory function of long noncoding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in breast cancer. We found that ...KCNQ1OT1 was significantly upregulated in breast cancer cell lines. In lentiviral-transduced BT-549 and HCC1599 cells, KCNQ1OT1 knockdown impaired cancer cell functions, including in vitro proliferation and migration, and in vivo transplant growth. The possible sponging target of KCNQ1OT1, human microRNA-107 (hsa-miR-107), was confirmed to be bound by KCNQ1OT1, and was upregulated in breast cancer cells with KCNQ1OT1 downregulation. Further, hsa-miR-107 knockdown in KCNQ1OT1-downregulated cancer cells reversed its impairing effects on cancer cell proliferation and migration in vitro. Thus, loss of KCNQ1OT1 is associated with functional impairment in breast cancer cells, likely through inverse regulation of its sponging target, hsa-miR-107.
Many populations of the two-spotted spider mite, Tetranychus urticae Koch, have developed high levels of resistance to the pesticide abamectin in China and other countries. This study developed a ...near-isogenic line to understand better the inheritance, cross-resistance, and fitness costs associated with abamectin resistance in the field population of T. urticae in China. We introduced the trait that confers extremely high abamectin resistance in a field-collected population of T. urticae into a susceptible laboratory strain (IPP-SS) to generate an abamectin-resistant near-isogenic line (NIL-Aba). This process was carried out through multiple backcrossing to IPP-SS and via parthenogenesis and abamectin screening. Compared with IPP-SS, the NIL-Aba strain had a 25 147-fold resistance to abamectin and a high level of cross-resistance to bifenthrin (288.17-fold), an intermediate level to emamectin benzoate (42.57-fold), and low levels to bifenazate, chlorfenapyr, cyflumetofen, cyenopyrafen, and cyetpyrafen with resistance ranging from 3.18- to 9.31-fold. But it had no cross-resistance to profenofos. The resistance to abamectin in NIL-Aba was autosomal, incompletely dominant, and polygenic. Based on two sex life table parameters, no fitness cost was found in NIL-Aba. Establishing the NIL-Aba strain provides a reliable basis for an in-depth study of abamectin resistance in T. urticae. New information on toxicological characteristics and fitness cost should facilitate the management of abamectin resistance in field populations of T. urticae.
Odorant‐binding proteins (OBPs) and chemosensory proteins (CSPs) of insects are thought to play roles in olfactory recognition affecting host choice, copulation, reproduction and other behaviors. ...Previous descriptions of OBPs and CSPs in the whitefly Bemisia tabaci often provided no or incomplete genetic information. In this study, we present a genome‐wide and transcriptome‐wide investigation of the OBPs and CSPs in B. tabaci MEAM1 (Middle East‐Asia Minor1 species). Eight OBP and 19 CSP genes were identified that covered all previous sequences. Phylogenetic analyses showed that the CSP genes had a lineage‐specific expansion (BtabBCSP1, BtabBCSP3, BtabBCSP13, BtabBCSP17, BtabBCSP18 and BtabBCSP19). Expression profiling of OBPs and CSPs by transcriptome sequencing and quantitative real‐time polymerase chain reaction (qPCR) revealed that expression patterns differed among developmental stages of B. tabaci MEAM1. Five OBP genes and 11 CSP genes significantly differed between males and females; four of the 19 CSP genes were highly expressed in adults, while two were highly expressed in nymphs. The expression profiles of the OBP and CSP genes in different tissues of B. tabaci MEAM1 adults were analyzed by qPCR. Four OBP genes found in B. tabaci MEAM1 were highly expressed in the head. Conversely, only two CSPs were enriched in the head, while the other six CSPs were specifically expressed in other tissues. Our results provide a foundation for future research on OBPs and CSPs in B. tabaci.
Hypertension is an essential regulator of cardiac injury and remodeling. However, the pathogenesis that contributes to cardiac hypertrophy remains to be fully explored. BRD4, as a bromodomain and ...extra-terminal (BET) family member, plays an important role in critical biological processes. In the study, our results showed that BRD4 expression was up-regulated in human and mouse hypertrophied hearts, and importantly these effects were modulated by reactive oxygen species (ROS) generation. In angiotensin II (Ang II)-treated cardiomyocytes, BRD4 decrease markedly blunted the prohypertrophic effect, which was further promoted by the combinational treatment of ROS scavenger (N-acetyl-cysteine, NAC). In addition, NAC pre-treatment markedly elevated the anti-fibrotic role of BRD4 suppression in Ang II-incubated cardiomyocytes by repressing transforming growth factor β1 (TGF-β1)/SMADs signaling pathway. NAC combined with BRD4 reduction further alleviated inflammation and oxidative stress in Ang II-exposed cardiomyocytes, which was partly through inhibiting nuclear factor-κB (NF-κB) signaling and improving nuclear erythroid factor 2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) pathway, respectively. Furthermore, the in vivo results confirmed the protective effects of BRD4 suppression on mice against aortic banding (AB)-induced cardiac hypertrophy, as evidenced by the reduced cross sectional area and fibrotic area using H&E and Masson trichrome staining. What’s more, the degree of cardiac hypertrophy (ANP and BNP), the expression of pro-fibrotic genes (TGF-β1, Collagen I, Collagen III and CTGF), the levels of inflammation and oxidative stress were all significantly attenuated by the blockage of BRD4 in AB-operated mice. Taken together, repressing BRD4 expression was found to confer a protective effect against experimental cardiac hypertrophy in mice, demonstrating its potential as an effective therapeutic target for pathological cardiac hypertrophy.
Scope
A growing body of evidence suggests that the harmful gut microbiota in depression patients can play a role in the progression of depression. There is limited research on troxerutin's impact on ...the central nervous system (CNS), especially in depression. The study finds that troxerutin effectively alleviates depression and anxiety‐like behavior in mice by increasing the abundance of beneficial bacteria like Lactobacillus and Firmicutes while decreasing the abundance of harmful bacteria like Proteobacteria, Bacteroides, and Actinobacteria in the gut. Furthermore, the research reveals that troxerutin regulates various metabolic pathways in mice, including nucleotide metabolism, caffeine metabolism, purine metabolism, arginine biosynthesis, histidine metabolism, 2‐oxocarboxylic acid metabolism, biosynthesis of amino acids, glycine, serine and threonine metabolism, and Arginine and proline metabolism.
Conclusions
In conclusion, the study provides compelling evidence for the antidepressant efficacy of troxerutin. Through the investigation of the role of intestinal microorganisms and metabolites, the study identifies these factors as key players in troxerutin's ability to prevent depression. Troxerutin achieves its neuroprotective effects and effectively prevents depression and anxiety by modulating the abundance of gut microbiota, including Proteobacteria, Bacteroides, and Actinobacteria, as well as regulating metabolites such as creatine.
Troxrutin, a natural flavonoid, has been found to regulate the gut microbiota and its microbial metabolism, with an antidepressant effect.
Several quorum sensing systems occurring in
Bacillus subtilis
, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate ...competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in
Bacillus velezensis
NAU-B3. We found that the
rapA4
and
phrA4
genes were co-transcribed in NAU-B3. When
rapA4
was expressed in the heterologous host
Bacillus subtilis
OKB105, surfactin production and sporulation were severely inhibited. However, when the
phrA4
was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase
srfA
gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the
srfA
operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment.
Key points
•Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42.
•RapA4-PhrA4 regulates surfactin production and sporulation.
•RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.
Since rockburst is a violent expulsion of rock in high geostress condition, this causes considerable damages to underground structures, equipments and most importantly presents serious menaces to ...workers' safety. Rockburst has been associated with thousands of accidents and casualties recently in China. Due to this importance, this research was intended to predict rockburst intensity based on fuzzy inference system (FIS) and adaptive neuro-fuzzy inference systems (ANFIS), and field measurements data. A total of 174 rockburst events were compiled from various published research works. Five different models were investigated. The maximum tangential stress, the uniaxial compressive strength, the uniaxial tensile strength of the surrounding rock and the elastic strain energy index were considered as the inputs while the actual rockburst intensity was the output. In some models, the inputs were extended to the stress coefficient and the rock brittleness coefficient. The results obtained from the study conclude that the knowledge-based FIS model shows lowest performance with 45.8%, 13.2%, 16.5% and 66.52% of the variance account for (VAF), root-mean square error (RMSE), mean absolute percentage error (MAPE) and the percentage of the successful prediction (PSP) indices, while the ANFIS model indicates the best performance with 92%, 1.71%, 0.94% and 95.6% of VAR, RMSE, MAPE and PSP indices, respectively. These results suggest that the developed models in the present study can be used for the rockburst prediction, and this may help to reduce the casualties sourced from the rockbursts.
► Five different fuzzy inference systems were developed for rockburst prediction. ► The models were calibrated using field data selected from published works. ► The results indicated that the models can predict rockburst in a reliable manner. ► The knowledge-based model yielded the lowest performance. ► The ANFIS model showed the best performance.
Abstract
Using quantum Monte Carlo, exact diagonalization, and perturbation theory, we study the spectrum of the
S
= 1/2 antiferromagnetic Heisenberg trimer chain by varying the ratio
g
=
J
2
/
J
...1
of the intertrimer and intratrimer coupling strengths. The doublet ground states of trimers form effective interacting
S
= 1/2 degrees of freedom described by a Heisenberg chain. Therefore, the conventional two-spinon continuum of width ∝
J
1
when
g
= 1 evolves into to a similar continuum of width ∝
J
2
when
g
→ 0. The intermediate-energy and high-energy modes are termed
doublons
and
quartons
which fractionalize with increasing
g
to form the conventional spinon continuum. In particular, at
g
≈ 0.716, the gap between the low-energy spinon branch and the high-energy band with mixed doublons, quartons, and spinons closes. These features should be observable in inelastic neutron scattering experiments if a quasi-one-dimensional quantum magnet with the linear trimer structure and
J
2
<
J
1
can be identified. Our results may open a window for exploring the high-energy fractional excitations.
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