•Plant flavonoids are important natural bioactive compounds.•Flavonoid classification and plants rich in flavonoids are summarized.•Flavonoid functions in biological processes in plants are ...reviewed.•Transcription factors regulate the biosynthesis of plant flavonoids.•Epidemic evidence, in vitro and in vivo studies reveal flavonoid bioactivity.
Flavonoids are a group of natural polyphenol substances abundant in vegetables, fruits, grains, and tea. As plant secondary metabolites, flavonoids play essential roles in many biological processes and responses to environmental factors in plants. Flavonoids are common in human diets and have antioxidant effects as well as other bioactivities (e.g., antimicrobial and anti-inflammatory properties), which reduce the risk of disease. Flavonoid bioactivity depends on structural substitution patterns in their C6-C3-C6 rings. However, reviews of plant flavonoid distribution and biosynthesis, as well as the health benefits of its bioactivity, remain scarce. Therefore, in the present review, we systematically summarize recent progress in the research of plant flavonoids, focusing on their biosynthesis (pathway and transcription factors) and bioactive mechanisms based on epidemic evidence, in vitro and in vivo research, and bioavailability in the human body. We also discuss future opportunities in flavonoid research, including biotechnology, therapeutic phytoproducts, and dietary flavonoids.
Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, ...diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations.
Circular RNAs (circRNAs) produced from back-splicing of exons of pre-mRNAs are widely expressed, but current understanding of their functions is limited. These RNAs are stable in general and are ...thought to have unique structural conformations distinct from their linear RNA cognates. Here, we show that endogenous circRNAs tend to form 16–26 bp imperfect RNA duplexes and act as inhibitors of double-stranded RNA (dsRNA)-activated protein kinase (PKR) related to innate immunity. Upon poly(I:C) stimulation or viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients with autoimmune disease systemic lupus erythematosus (SLE). Importantly, overexpression of the dsRNA-containing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE.
Display omitted
•circRNAs are globally degraded by activated RNase L upon viral infection•Many circRNAs tend to form 16–26 bp duplexes and act as endogenous PKR inhibitors•The RNase L-mediated circRNA degradation is required for PKR activation•circRNA reduction and aberrant PKR activation are found in autoimmune disease SLE
The unique structure of circRNAs allows them to bind and regulate the innate immune dsRNA receptor PKR, and misregulation of this process is found in patients with autoimmune disease.
Evidence has shown that phosphorus (P) deposited in sediments over multiple decades can be released by microbial activities, leading to recurring harmful algal blooms in several lakes. Sediment ...microbial fuel cells (SMFC) have been identified as an alternative in-situ approach for limiting P release from sediments to overlying water. However, the effects of SMFC on the micro-environment (pH) in vicinity of the electrodes, which could impact the P distribution, have often been ignored. This study successfully established SMFC systems to investigate their influence on P species and spatial distributions in lake sediments. The results showed that pH was relatively stable in the control group (6.8), while in the SMFC group the pH ranged from 4.63 to 8.26 along the sediment-water profile, suggesting that pH was highly affected by the SMFC system. The overlying water P concentration was much lower in the SMFC group (0.05 mg/L) than the control group (0.14 mg/L). However, P concentration in the sediment pore water of the SMFC group increased from 0.018 to 1.090 mg/L with depth. P fractions in the upper 4 cm of the sediments were highly affected by SMFC operation, but P fractions (i.e., NH4Cl–P, BD-P, and OP) in the SMFC group were not significantly correlated with SRP (p > 0.05). There was a strong correlation between the soluble reactive P (SRP) in pore water and pH (r = −0.930, p < 0.01), suggesting that SRP in pore water was significantly affected by the pH decrease induced by SMFC.
Display omitted
•SMFC was an effective approach to minimize P release to overlying water.•The influence of SMFC on P vertical distribution in the sediment was studied.•pH in SMFC group had wide range from 4.63 to 8.26 in the sediment-water profiles.•P fractions in the upper 4 cm of the sediment were highly affected by SMFC operation.•The vertical distributions of SRP and Fe2+ were highly correlated with pH in SMFC.
Background Gut microbiota may play a role in the natural history of cow's milk allergy. Objective We sought to examine the association between early-life gut microbiota and the resolution of cow's ...milk allergy. Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43; ANOVA P = .034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy.
Two new crystalline thioarsenate compounds, formulated as pipH2Mn2As2S6 (1) and TMDPH2As4S6 (2) (pip = piperazine, TMDP = 1,3-bis(4-piperidyl)propane), have been surfactant–thermally synthesized ...with the utilization of octylamine and PEG-400 as the solvents. The crystal structure of 1 features Mn2As2S6 n 2n– anionic layers which are separated by doubly protonated pipH22+ cations, while that of compound 2 is made of discrete As4S62– clusters and doubly protonated TMDPH22+ cations. Both compounds were characterized by powder X-ray diffraction analyses, solid-state optical diffuse reflectance spectroscopy, and thermogravimetric analyses. As estimated from the adsorption spectra, the band gaps of 1 and 2 are 2.32 and 2.49 eV, respectively. The electronic structure calculations based on density functional theory method confirm the indirect band gap of 2. In addition, the magnetic investigation of 1 suggests antiferromagnetic behavior. Since compound 2 crystallizes in the space group Imm2, the nonlinear optical property of 2 was studied, and its second harmonic generation intensity was nearly twice as much as that of KDP. Furthermore, compounds 1 and 2 exhibited a photocurrent response with the photocurrent intensities of 17.5 μA/cm2 and 2 μA/cm2, respectively.
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find ...early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355;
P
< 0.001) and miR-34a-5p (logOR 6.955;
P
< 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586;
P
< 0.001) and miR-140-5p (logOR 6.373;
P
< 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.
Background:
The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This ...study aims at estimating the prevalence of DOAC off-label doses in AF patients.
Methods:
Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses.
Results:
A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19–28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16–24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban;
P
interaction
=
0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3–7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4–6%).
Conclusion:
This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.
•Dc can be predicted using linear equations of hydraulic parameters except τ.•Dc can be well predicted with V, ω, and E.•V is a preferred hydraulic parameter for estimating Dc by rill flow.
The ...relationship between soil detachment capacity (Dc) by rill flow and hydraulic parameters (e.g., flow velocity, shear stress, unit stream power, stream power, and unit energy) at low flow rates is investigated to establish an accurate experimental model. Experiments are conducted using a 4×0.1m rill hydraulic flume with a constant artificial roughness on the flume bed. The flow rates range from 0.22×10−3m2s−1 to 0.67×10−3m2s−1, and the slope gradients vary from 15.8% to 38.4%. Regression analysis indicates that the Dc by rill flow can be predicted using the linear equations of flow velocity, stream power, unit stream power, and unit energy. Dc by rill flow that is fitted to shear stress can be predicted with a power function equation. Predictions based on flow velocity, unit energy, and stream power are powerful, but those based on shear stress, especially on unit stream power, are relatively poor. The prediction based on flow velocity provides the best estimates of Dc by rill flow because of the simplicity and availability of its measurements. Owing to error in measuring flow velocity at low flow rates, the predictive abilities of Dc by rill flow using all hydraulic parameters are relatively lower in this study compared with the results of previous research. The measuring accuracy of experiments for flow velocity should be improved in future research.
Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease
, evidence of lupus-causing TLR7 gene variants is ...lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA
,
and binds to guanosine
-
. We identified a de novo, previously undescribed missense TLR7
variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7
variant selectively increased sensing of guanosine and 2',3'-cGMP
, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c
age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7
mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.
PDF
