Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an ...attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP‐qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR‐433, while dual luciferase assay was carried out to confirm the targeting relationship between miR‐433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo‐tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A‐miR‐433‐FXYD3‐PI3K‐AKT axis in the progression of HCC after loss‐ and gain‐function assays. KDM5A p‐p85 and p‐AKT were highly expressed but miR‐433 was down‐regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR‐433 by demethylating H3K4me3 on its promoterregion. miR‐433 negatively targeted FXYD3. Depleting miR‐433 or re‐expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down‐regulated miR‐433 and up‐regulated FXYD3‐PI3K‐AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3‐PI3K‐AKT axis to enhance angiogenesis in HCC by suppressing miR‐433.
Black phosphorus nanoparticles (BP NPs) possess great advantages in photocatalysis owing to the rich surface active sites, extremely high carrier mobility, and strong visible–near-infrared light ...response. However, the complex preparation process, poor stability, and rapid carrier recombination restrict their successful application in photocatalysis. Herein, the above problems are resolved by preparing BP NPs through a facile sonication-assisted hydrothermal method. To further improve the stability and photocatalytic activity, BP NPs are tightly anchored onto ZnS to prepare ZnS–BP porous nanosheets. With the Zn–P coordination bond built between them, higher stability, enhanced carrier transport ability, and excellent hydrogen adsorption and desorption equilibrium of photocatalysts are achieved. An efficient and recyclable photocatalytic hydrogen evolution rate of 1561 μmol h–1 g–1 is obtained under visible-light irradiation, which is superior to that of previously reported BP-based photocatalysts. Besides, the photocatalytic mechanism is investigated based on the theoretical calculations and experimental characterizations. The charge transfer dynamics are studied by surface photovoltage (SPV), ultrafast transient absorption (TA), X-ray absorption spectra (XAS), electrochemical impedance spectroscopy (EIS), and steady-state photoluminescence (PL) spectra. This work set a reference for the design of high-performance BP-related nanomaterials in solar energy storage and conversion.
Objective
The treatment strategy and timing of ureteropelvic junction obstruction (UPJO) in infants remain controversial. This study aimed to compare the effect of early surgical treatment (EST) and ...conservative treatment (CT) on neonates and infants with UPJO and their recovery of renal function and morphology.
Methods
Eighty neonates and infants with severe hydronephrosis were enrolled in this study. They received early pyeloureteroplasty or CT. Diethylenetriamine pentaacetate was used to assess renal function.
Results
There were no significant differences in renal function or renal indices at baseline between the two groups. At 3 and 6 months of follow-up, the anteroposterior diameter of the renal pelvis and the Society of Fetal Urology grade in the EST surgery group were significantly lower compared with those at baseline. The thickness of the renal cortex was greater in the EST group than in the CT group at 3 and 6 months of follow-up. After follow-up for 6 months, renal function in the EST group was significantly better than that in the CT group.
Conclusion
EST accelerates the recovery of renal morphological and functional indices in neonates and infants with severe hydronephrosis.
Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, ...regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound
exhibited most excellent anti-proliferation activities against SW620 cells with IC
of 0.86 ± 0.02 µM than Celecoxib (IC
= 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound
as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.
Combining unmanned aerial vehicles (UAVs) with 6G, Internet of Things (IoT) and other emerging communication technologies could better satisfy various IoT applications and create more innovative ...services. This paper develops a novel hierarchical 6G IoT network with UAVs in the sky and intelligent reflective surface (IRS) equipped. The system employs backscattering communication (BackCom) to transmit data in a free-ride manner. Through beamforming, IRS enhances the energy of the reflectable signal, thereby improving the distance and performance of the BackCom. Simulation results reveal that our approach makes a significant improvement to the performance of the whole system and takes obvious advantage over traditional solutions.
The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: ...PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P < 0.05). Pathway enrichment analysis was performed on MetaCore™ to search the molecular pathways associated with the gene expression profile of PV, compared with vehicle and BA. Compared with vehicle, we found that 60% of the top 10 pathways in PV group were related to immune response. The top 10 biological processes of the targeted pathways were mainly related to the multiple immunomodulatory process of neuro-vascular inflammation, including immune_Th17-deried cytokins, regulation of angiogenesis, cell adhesion_Leucocyte chemotaxis, antigen presentation, cell adhesion_synaptic contact, and inflammation related to Amphoterin signaling. Moreover, compared with BA, 17 pathways of PV were identified, and 58.82% (10/17) were also related to immune response, especially, half of the top 10 pathways with the lower p-value. In these top 10 pathways, 4 were the cytokine-mediated signaling pathways, which play key role in inflammation, like IL-17 signaling pathways with the activation of G-CSF,IL-23,RANKL, p38MAPK and NF-κB.These findings indicate that PV may be an efficacious pluripotent anti-inflammatory agent against cerebral ischemic-reperfusion injury by targeting on multiple immunomodulatory process of neuro-vascular inflammation.
Phytohormones are key regulators of plant growth, development, and signalling networks involved in responses to diverse biotic and abiotic stresses. Transcriptional reference maps of hormone ...responses have been reported for several model plant species such as Arabidopsis thaliana, Oryza sativa, and Brachypodium distachyon. However, because of species differences and the complexity of the wheat genome, these transcriptome data are not appropriate reference material for wheat studies.
We comprehensively analysed the transcriptomic responses in wheat spikes to seven phytohormones, including indole acetic acid (IAA), gibberellic acid (GA), abscisic acid (ABA), ethylene (ET), cytokinin (CK), salicylic acid (SA), and methyl jasmonic acid (MeJA). A total of 3386 genes were differentially expressed at 24 h after the hormone treatments. Furthermore, 22.7% of these genes exhibited overlapping transcriptional responses for at least two hormones, implying there is crosstalk among phytohormones. We subsequently identified genes with expression levels that were significantly and differentially induced by a specific phytohormone (i.e., hormone-specific responses). The data for these hormone-responsive genes were then compared with the transcriptome data for wheat spikes exposed to biotic (Fusarium head blight) and abiotic (water deficit) stresses.
Our data were used to develop a transcriptional reference map of hormone responses in wheat spikes.
Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently ...in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/α, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/α and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation.
The spikelet number per spike (SNS) contributes greatly to grain yield in wheat. Identifying various genes that control wheat SNS is vital for yield improvement. This study used a recombinant inbred ...line population genotyped by the Wheat55K single-nucleotide polymorphism array to identify two major and stably expressed quantitative trait loci (QTLs) for SNS. One of them (QSns.sau-2SY-2D.1) was reported previously, while the other (QSns.sau-2SY-7A) was newly detected and further analyzed in this study. QSns.sau-2SY-7A had a high LOD value ranging from 4.46 to 16.00 and explained 10.21–40.78％ of the phenotypic variances. QSns.sau-2SY-7A was flanked by the markers AX-110518554 and AX-110094527 in a 4.75-cM interval on chromosome arm 7AL. The contributions and interactions of both major QTLs were further analyzed and discussed. The effect of QSns.sau-2SY-7A was successfully validated by developing a tightly linked kompetitive allele specific PCR marker in an F2:3 population and a panel of 101 high-generation breeding wheat lines. Furthermore, several genes including the previously reported WHEAT ORTHOLOG OF APO1 (WAPO1), an ortholog of the rice gene ABERRANT PANICLE ORGANIZATION 1 (APO1) related to SNS, were predicted in the interval of QSns.sau-2SY-7A. In summary, these results revealed the genetic basis of the multi-spikelet genotype of wheat line 20828 and will facilitate subsequent fine mapping and breeding utilization of the major QTLs.
ATP-binding cassette (ABC) transporters hydrolyze ATP to transport a wide range of substrates.
is a major causal agent of Fusarium head blight, which is a severe disease in wheat worldwide.
(
) ...encodes an ABC-C (ABC transporter family C) transporter in
, which was highly expressed during the infection in wheat and was up-regulated by the plant defense hormone salicylic acid (SA) and the fungicide tebuconazole. The predicted tertiary structure of the FgABCC9 protein was consistent with the schematic of the ABC exporter. Deletion of
resulted in decreased mycelial growth, increased sensitivity to SA and tebuconazole, reduced accumulation of deoxynivalenol (DON), and less pathogenicity towards wheat. Re-introduction of a functional
gene into Δ
recovered the phenotypes of the wild type strain. Transgenic expression of
in
increased the accumulation of SA in its leaves without activating SA signaling, which suggests that
functions as an SA exporter. Taken together,
encodes an ABC exporter, which is critical for fungal exportation of SA, response to tebuconazole, mycelial growth, and pathogenicity towards wheat.
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