Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause ...of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown.
High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823.
Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823.
Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
A pre-metastatic niche is a microenvironment prepared for the colonization of circulating tumor cells in specific organs. Exosomes are extracellular vesicles with a variety of biological functions. ...Exosomes play an irreplaceable role in the development of pre-metastatic niches, and mainly function as communication medium. In this review, we analyzed the effects of exosomes on pre-metastatic niches from various perspectives, including inflammation, immune response, angiogenesis, organotropism, matrix remodeling and biomarker expression. In particular, exosomes express programmed death ligand 1 (PD-L1) and cause the immune escape of tumor cells. The immunomodulatory effects of exosomes and their potential in liquid diagnosis have drawn our attention. The potential value of exosomes and pre-metastatic niches will be realized in the field of immunity therapy.
The role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 ...transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.
Suppose that the vertex set of a connected graph
G
is
V
(
G
)
=
{
v
1
,
…
,
v
n
}
. Then we denote by
T
r
G
(
v
i
)
the sum of distances between
v
i
and all other vertices of
G
. Let
Tr
(
G
) be the
...n
×
n
diagonal matrix with its (
i
,
i
)-entry equal to
T
r
G
(
v
i
)
and
D
(
G
) be the distance matrix of
G
. Then
Q
D
(
G
)
=
T
r
(
G
)
+
D
(
G
)
is the distance signless Laplacian matrix of
G
. The largest eigenvalues of
Q
D
(
G
)
is called distance signless Laplacian spectral radius of
G
. In this paper we give some graft transformations on distance signless Laplacian spectral radius of the graphs and use them to characterize the graphs with the minimum and maximal distance signless Laplacian spectral radius among non-starlike and non-caterpillar trees.
Childhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 ...healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain's self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.
The world is currently facing a critical issue of water pollution, with wastewater being a major contributor. It comes from different types of pollutants, including industrial, medical, agricultural, ...and domestic. Effective treatment of wastewater requires efficient degradation of pollutants and carcinogens prior to discharge. Commonly used methods for wastewater treatment include filtration, adsorption, biodegradation, advanced oxidation processes, and Fenton oxidation, among others.The sonochemical effect refers to the decomposition, oxidation, reduction, and other reactions of pollutant molecules in wastewater upon ultrasound activation, achieving pollutants removal. Furthermore, the micro-flow effect generated by ultrasonic waves creates tiny bubbles and eddies. This significantly increases the contact area and exchange speed of pollutants and dissolved oxygen, thereby accelerating pollutant degradation. Currently, ultrasonic-assisted technology has emerged as a promising approach due to its strong oxidation ability, simple and cheap equipments, and minimal secondary pollution. However, the use of ultrasound in wastewater treatment has some limitations, such as high energy consumption, lengthy treatment time, limited water treatment capacity, stringent water quality requirements, and unstable treatment effects. To address these issues, the combination of enhanced ultrasound with nanotechnology is proposed and has shown great potential in wastewater treatment. Such a combination can greatly improve the efficiency of ultrasonic oxidation, resulting in an improved performance of wastewater purification. This article presents recent progress in the development of sonoactivated nanomaterials for enhanced wastewater disposal. Such nanomaterials are systematically classified and discussed. Potential challenges and future prospects of this emerging technology are also highlighted.
Childhood maltreatment (CM) is regarded as an important risk factor for major depressive disorder (MDD). However, the neural links corresponding to the process of early CM experience producing brain ...alterations and then leading to depression later remain unclear. To explore the neural basis of the effects of CM on MDD and the potential role of microRNA-9 (miR-9) in these processes, we recruited 40 unmedicated MDD patients and 34 healthy controls (HCs) to complete resting-state fMRI scans and peripheral blood miR-9 tests. The neural substrates of CM, miR-9, and depression, as well as their interactive effects on intrinsic amygdala functional connectivity (AFC) networks were investigated in MDD patients. Two-step mediation analysis was separately employed to explore whether AFC strength mediates the association among CM severity, miR-9 levels, and depression. A support vector classifier (SVC) model of machine learning was used to distinguish MDD patients from HCs. MDD patients showed higher miR-9 levels that were negatively correlated with CM scores and depressive severity. Overlapping effects of CM, miR-9, and depressive severity on bilateral AFC networks in MDD patients were primarily located in the prefrontal-striatum pathway and limbic system. The connection of amygdala to prefrontal-limbic circuits could mediate the effects of CM severity on the miR-9 levels, as well as the impacts of miR-9 levels on the severity of depression in MDD patients. Furthermore, the SVC model, which integrated miR-9 levels, CM severity, and AFC strength in prefrontal-limbic regions, had good power in differentiating MDD patients from HCs (accuracy 85.1%). MiR-9 may play a crucial role in the process of CM experience-produced brain changes targeting prefrontal-limbic regions and that subsequently leads to depression. The present neuroimaging-epigenetic results provide new insight into our understanding of MDD pathophysiology.
Suicide ideation (SI) is a most high-risk clinical sign for major depressive disorder (MDD). However, whether the rich-club network organization as a core structural network is associated with SI and ...how the related neural circuits are distributed in MDD patients remain unknown. Total 177 participants including 69 MDD patients with SI (MDDSI), 58 MDD without SI (MDDNSI) and 50 cognitively normal (CN) subjects were recruited and completed neuropsychological tests and diffusion-tensor imaging scan. The rich-club organization was identified and the global and regional topological properties of structural networks, together with the brain connectivity of specific neural circuit architectures, were analyzed. Further, the support vector machine (SVM) learning was applied in classifying MDDSI or MDDNSI from CN subjects. MDDSI and MDDNSI patients both exhibited disrupted rich-club organizations. However, MDDSI patients showed that the differential network was concentrated on the non-core low-level network and significantly destroyed betweeness centrality was primarily located in the regional non-hub regions relative to MDDNSI patients. The differential structural network connections involved the superior longitudinal fasciculus and the corpus callosum were incorporated in the cognitive control circuit and default mode network. Finally, the feeder serves as a potentially powerful indicator for distinguishing MDDSI patients from MDDNSI or CN subjects. The altered rich-club organization provides new clues to understand the underlying pathogenesis of MDD patients, and the feeder was useful as a diagnostic neuroimaging biomarker for differentiating MDD patients with or without SI.
Background
Root-associated microbiomes are important for plant nutrient uptake, disease suppression and plant growth. It is important to reveal wheat-root associated microbial community assembly and ...dominant drivers determining their variability.
Methods
Using 16S rRNA gene profiling, we investigated the effects of sample type, location, growth stage and variety on prokaryotic communities in the root endosphere and rhizosphere of wheat and bulk soil based on the field samples including 5 varieties from 4 locations along similar latitude with the distance about 157 to 800 km apart between any two locations.
Results
Prokaryotic communities were more diverse in the bulk soil and rhizosphere than in root endosphere. Wheat-root associated prokaryotic community assembly was shaped predominantly by sample type, while within each sample type, location had stronger effects on the variation in prokaryotic community than growth stage or variety. Wheat variety effects varied substantially among different locations and growth stages in root endosphere and rhizosphere samples, and the variety effects were location-specific and growth stage-specific. Root endosphere specially enriched
Pseudomonas
, relative to other two sample types, while rhizosphere mainly enriched
Bacillus
.
Conclusions
This study characterized prokaryotic communities of wheat-root endosphere and rhizosphere and their relationships, and demonstrated significant interactive effects between wheat variety, location and growth stage on prokaryotic community assembly in field condition.
In this paper, we investigate the following Kirchhoff-type equation
-
M
∫
R
N
|
∇
u
|
p
d
x
Δ
p
u
=
|
u
|
p
∗
-
2
u
+
h
(
x
)
|
u
|
q
-
2
u
,
x
∈
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,
where
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≥
3
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p
<
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,
p
∗
=
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-
p
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0
<
...h
∈
L
p
∗
p
∗
-
q
(
R
N
)
with
q
∈
(
1
,
p
∗
)
;
M
is a nonnegative continuous function with some growth conditions. We show that the above problem has infinitely many solutions by using variational methods.
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