infection consistently leads to chronic and low degree of inflammatory response in gastric mucosa and is closely related with gastrointestinal and extra-gastric diseases. Effects of local microbiome ...in the stomach have been studied in adults and children with
infection. It is, however, not known whether the intestinal microbial community differs in children with varying
infection. The aim of this study is to characterize the altered composition of microbiome induced by
infection and in gastritis.
This study involved 154 individuals, including 50 children affected by
-induced gastritis, 42 children with
-negative gastritis, and 62 healthy controls. Gut microbiome composition was analyzed using 16S rRNA gene-based pyrosequencing. Fecal bacterial diversity and composition were then compared.
On the basis of an analysis of similarities and differences, we found that children with
-induced gastritis exhibited gut bacteria dysbiosis. The ratio of Firmicutes/Bacteroidetes (F:B) at the phylum level had dramatically decreased in
-positive gastritis group (HPG) and
-negative gastritis group (HNG), compared with the healthy control group (HCG). At the family and genus levels, relative abundance of Bacteroidaceae and Enterobacteriaceae was prevalent in HPG and HNG, whereas relative abundance of Lachnospiraceae, Bifidobacteriaceae, and Lactobacillaceae was seen in HCG. Prevalence of different taxa of gut microbiome at the class, order, family, and genus levels was also observed among the three groups.
Gastritis can cause changes in composition of fecal microbiome, which is exacerbated by
infection. These changes in gut microbiome may be related to drug resistance and development of chronic gastrointestinal diseases.
The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long ...noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching mechanism underlying both initiation and progression of aggressive PCa.
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•rs11672691 risk region is bifunctional with both promoter and enhancer activity•This SNP modulates the bifunctionality and reciprocal expression of PCAT19 isoforms•PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes•PCAT19-long regulates cell proliferation, tumor growth, and metastasis
Transcription factor binding site remodeling by a risk allele for aggressive prostate cancer results in conversion of a promoter to an enhancer with downstream consequences on long noncoding RNA isoform expression and oncogenesis.
Biological treatment of wastewater always leaves plenty of refractory dissolved organic matters (DOM) in effluents, specifically for fresh waste leachate. Aiming at comprehending the production and ...removal of these compounds, this study investigated DOM transformation in a simultaneous denitrification and methanogenesis with activated sludge (SDM-AS) system with NO3−/NO2− backflow for raw fresh leachate. Chemical oxygen demand (COD) was reduced to 854 ± 120 mg/L from 63000 ± 470 mg/L, and total nitrogen (TN) decreased from 2500 ± 647 mg/L to 404 ± 75 mg/L, during an operation of 440 days. The SDM reactor was fed at organic loading rate of 6.70 kgCOD/(m3·d) to generate 2.52 L CH4/(L·d). Molecular information of leachate DOM was acquired by using ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry. A DOM classification based on Venn diagram was proposed to divide leachate DOM into seven categories. It revealed that 76–84% of final effluent DOM stemmed from biological derivation. Posteriori non-target screening showed anthropogenic micropollutants, e.g. phosphate flame retardants and industrial agents, probably contributed to the remnant native inert DOM in the effluent at the levels of 5–200 μg/L. DOM Classification also showed a portion of bio-derived DOM can be completely removed by SDM-AS processes, while the rest bio-derived DOM can be partially removed depending on DOM nature and the recirculation ratio. The removal and production rate of a specific bio-derived molecule in respective SDM and AS units theoretically satisfied a hyperbolical and dual relationship in terms of mass balance. The persistence of each DOM category was sorted. These results showed anaerobic degradation could be a promising approach to reduce aerobic bio-derived DOM.
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•A DOM classification was proposed to recognize remnant DOM composition in effluent.•The persistence of classified DOM categories was compared.•Bio-derived DOM accounted for 76–84% of effluent DOM as recalcitrant fraction.•Production and removal of bio-derived DOM meet a hyperbolical relationship.
In order to improve the sensitivity of the pure MoO 3 sensor to ammonia and reduce its operating temperature, MoO 3 /MoS 2 /rGO was prepared in this work, and the gas-sensitive performance of MoO 3 .../MoS 2 /rGO was studied. The results of the static gas sensitivity test show that, compared with pure MoO 3 , MoO 3 /MoS 2 /rGO greatly improves the response of the sensor to ammonia at low temperature. Moreover, this article discusses the multigas detection methods by waveform-matched dynamic temperature modulation based on low-temperature gas sensor composites of rose-like MoO 3 /MoS 2 /rGO, which is used to solve the shortcoming of poor selectivity of metal-oxide-semiconductor gas sensor. Multigas (including acetone, methanol, ethanol, benzene, toluene, and ammonia) detection methods by waveform-matched dynamic temperature modulation are investigated, in which the experimental results show that the dynamic response curves of the sensor have obvious differences to each gas under different temperature waveform modulations. Temperature modulation waveforms with different periods and variations are investigated, including rectangular wave, triangular wave, and sine wave. This provides a feasible way to improve the selectivity of the sensor. In order to establish and verify the accuracy of the multigas detection model, 100 sets of response curves are selected for each waveform. Finally, the gas-sensing mechanism of gas-sensitive materials to ammonia is analyzed. Preparation of highly sensitive materials, dynamic testing, and gas identification methods can provide the technical basis for the application of gas sensors.
Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and ...metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots.
First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content.
The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-β-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.
The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ...ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ∼90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.
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•Ultra-deep rRNA-depleted RNA sequencing of 144 localized prostate tumors•Fusion gene profiles differentiate localized from metastatic disease•Widespread RNA circularization events define clinically distinct tumor subtypes•Functional screening reveals pervasive circular isoform-specific essentiality
RNA circularization is a pervasive feature of prostate cancer, with hundreds of circRNAs promoting cell proliferation through functions distinct from their parental linear RNA.
N6-Methyladenosine (m6A) accounts for approximately 0.2% to 0.6% of all adenosine in mammalian mRNA, representing the most abundant internal mRNA modifications. m6A RNA immunoprecipitation followed ...by high-throughput sequencing (MeRIP-seq) is a powerful technique to map the m6A location transcriptome-wide. However, this method typically requires 300 μg of total RNA, which limits its application to patient tumors. In this study, we present a refined m6A MeRIP-seq protocol and analysis pipeline that can be applied to profile low-input RNA samples from patient tumors. We optimized the key parameters of m6A MeRIP-seq, including the starting amount of RNA, RNA fragmentation, antibody selection, MeRIP washing/elution conditions, methods for RNA library construction, and the bioinformatics analysis pipeline. With the optimized immunoprecipitation (IP) conditions and a postamplification rRNA depletion strategy, we were able to profile the m6A epitranscriptome using 500 ng of total RNA. We identified approximately 12,000 m6A peaks with a high signal-to-noise (S/N) ratio from 2 lung adenocarcinoma (ADC) patient tumors. Through integrative analysis of the transcriptome, m6A epitranscriptome, and proteome data in the same patient tumors, we identified dynamics at the m6A level that account for the discordance between mRNA and protein levels in these tumors. The refined m6A MeRIP-seq method is suitable for m6A epitranscriptome profiling in a limited amount of patient tumors, setting the ground for unraveling the dynamics of the m6A epitranscriptome and the underlying mechanisms in clinical settings.
The perception of susceptible individuals naturally lowers the transmission probability of an infectious disease but has been often ignored. In this paper, we formulate and analyze a diffusive SIS ...epidemic model with memory-based perceptive movement, where the perceptive movement describes a strategy for susceptible individuals to escape from infections. We prove the global existence and boundedness of a classical solution in an
n
-dimensional bounded smooth domain. We show the threshold-type dynamics in terms of the basic reproduction number
R
0
: when
R
0
<
1
, the unique disease-free equilibrium is globally asymptotically stable; when
R
0
>
1
, there is a unique constant endemic equilibrium, and the model is uniformly persistent. Numerical analysis exhibits that when
R
0
>
1
, solutions converge to the endemic equilibrium for slow memory-based movement and they converge to a stable periodic solution when memory-based movement is fast. Our results imply that the memory-based movement cannot determine the extinction or persistence of infectious disease, but it can change the persistence manner.
Objective
Impaired wound healing in diabetes mellitus (DM) is a major health burden on patients, their families, and society. The present study aimed to systematically profile the m6A modification ...landscape in cutaneous wounds in a diabetic mouse model.
Approach
Diabetes was induced in mice through a single intraperitoneal injection of streptozotocin (STZ); a single intraperitoneal injection of PBS was made in control mice for comparisons. Both groups then received an 8-mm diameter, full-thickness dorsal body wound with a biopsy punch. Five days after wound surgery, western blot analysis of harvested wound tissues from both groups was used to assess the expression of m6A-related enzymes. Genome-wide profiling of m6A-tagged transcripts was performed through MeRIP-seq and RNA-seq.
Results
ALKBH5, an m6A eraser, was significantly upregulated, while METTL3, METTL14, and WTAP, m6A writers, were markedly downregulated in the diabetic wounds. Additionally, a total of 1335 m6A peaks were differentially expressed in MeRIP-seq and RNA-seq analyses, with 558 upregulated and 777 downregulated peaks. Finally, there was hypomethylated and hypermethylated differentiation at the gene and transcript levels.
Innovation
The present study was the first to reveal the m6A landscape in diabetic wounds in an animal model.
Conclusion
This study, by deeply analyzing the role of m6A modifications in diabetic wound healing, provides new insights and understanding into the molecular mechanisms of diabetic wound healing. Future research could further explore how m6A modifications regulate the wound healing process, thereby offering new potential targets for the treatment of diabetic wounds.
Abstract
Mutations in mitochondrial DNA (mtDNA) play critical roles in many human diseases. In vivo visualization of cells bearing mtDNA mutations is important for resolving the complexity of these ...diseases, which remains challenging. Here we develop an integrated nano Cas12a sensor (InCasor) and show its utility for efficient imaging of mtDNA mutations in live cells and tumor-bearing mouse models. We co-deliver Cas12a/crRNA, fluorophore-quencher reporters and Mg
2+
into mitochondria. This process enables the activation of Cas12a’s trans-cleavage by targeting mtDNA, which efficiently cleave reporters to generate fluorescent signals for robustly sensing and reporting single-nucleotide variations (SNVs) in cells. Since engineered crRNA significantly increase Cas12a’s sensitivity to mismatches in mtDNA, we can identify tumor tissue and metastases by visualizing cells with mutant mtDNAs in vivo using InCasor. This CRISPR imaging nanoprobe holds potential for applications in mtDNA mutation-related basic research, diagnostics and gene therapies.
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