The rapid development of 5G network technology has gained much popularity as well as concerns about its adverse effects. In this study, we investigated the effects of 4.9 GHz (one of working ...frequencies of 5G communication) radiofrequency (RF) field on emotional behaviours and spatial memory in adult male mice. Open field test (OFT), tail suspension test (TST) and Y maze were used to evaluate anxiety, depression-like behaviour and spatial memory ability, respectively. It was found that the anxiety-like behaviour and spatial memory ability of mice did not change, but the depression-like behaviour was induced in mice after 4.9 GHz RF exposure. In addition, the number of neurons significantly reduced and the level of pyroptosis obviously increased in amygdala rather than hippocampus. These results suggested that 4.9 GHz RF exposure could induce depression-like behaviour, which might be associated with the neuronal pyroptosis in amygdala.
Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional ...Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs) into intermediate neural progenitors (INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment.
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•miR-342-5p acts as a downstream effector of canonical Notch signaling•Notch signal inhibits miR-342-5p expression by regulating its host gene Evl•miR-342-5p promotes the transition of NSCs into INPs•Astrocyte commitment was suppressed by miR-342-5p targeting GFAP
In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP.
Biflavones from Ginkgo biloba are naturally occurring inhibitors of human thrombin.
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•The inhibition of major constituents in Ginkgo biloba on human thrombin were assayed.•Four ...biflavones and five flavonoids were found with thrombin inhibition activity.•Four biflavones were mixed inhibitors against human thrombin.•Ginkgetin could bind on human thrombin at exosite I rather than exosite II.
Ginkgo Biloba leaf extract has been widely used for the prevention and treatment of thrombosis and cardiovascular disease in both eastern and western countries, but the bioactive constituents and the underlying mechanism of anti-thrombosis have not been fully characterized. The purpose of this study was to investigate the inhibitory effects of major constituents in Ginkgo biloba on human thrombin, a key serine protease regulating the blood coagulation cascade and the processes of thrombosis. To this end, a fluorescence-based biochemical assay was used to assay the inhibitory effects of sixteen major constituents from Ginkgo biloba on human thrombin. Among all tested natural compounds, four biflavones (ginkgetin, isoginkgetin, bilobetin and amentoflavone), and five flavonoids (luteolin, apigenin, quercetin, kaempferol and isorhamnetin) were found with thrombin inhibition activity, with the IC50 values ranging from 8.05 μM to 82.08 μM. Inhibition kinetic analyses demonstrated that four biflavones were mixed inhibitors against thrombin-mediated Z-GGRAMC acetate hydrolysis, with the Ki values ranging from 4.12 μM to 11.01 μM. Molecular docking method showed that the four biflavones could occupy the active cavity with strong interactions of salt bridges and hydrogen bonds. In addition, mass spectrometry-based lysine labeling reactivity assay suggested that the biflavones could bind on human thrombin at exosite I rather than exosite II. All these findings suggested that the biflavones in Ginkgo biloba were naturally occurring inhibitors of human thrombin, and these compounds could be used as lead compounds for the development of novel thrombin inhibitors with improved efficacy and high safety profiles.
Abstract
Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant–insect ...interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1–NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant–insect interactions and suggests the potential origin of orphan salivary genes.
Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory ...mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non-small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis.
Ceramidases (CDases) are vital sphingolipid enzymes involved in organismal growth and development. They have been reported as key mediators of thermal stress response. However, whether and how CDase ...responds to heat stress in insects remain unclear. Herein, we identified two CDase genes,
alkaline ceramidase (
) and neutral ceramidase (
), by searching the transcriptome and genome databases of the mirid bug,
, an important natural predator of planthoppers. Quantitative PCR (qPCR) analysis showed that both
and
were highly expressed in nymphs than in adults.
was especially highly expressed in the head, thorax, and legs, while
was widely expressed in the tested organs. Only the
transcription was significantly affected by heat stress. Knocking down
increased the
nymph survival rate under heat stress. The transcriptome and lipidomics data showed that the RNA interference-mediated suppression of
significantly upregulated the transcription level of
(
) and the content of long-chain base ceramides, including C16-, C18-, C24-, and C31- ceramides. In
nymphs,
played an important role in heat stress response, and the upregulation of nymph survival rate might be caused by variation in the ceramide levels and transcriptional changes in
downstream genes. This study improves our understanding of the physiological functions of insect CDase under heat stress and provides valuable insights into the nature enemy application.
The study aimed to elucidate abscopal effects of thoracic X-ray irradiation on spermatogenesis in mice. Male
C57BL
/
6
mice were randomly divided into sham group and radiation group, and subjected to ...thorax fractionated X-ray irradiation or sham irradiation with the total dose of 5 Gy/day for each animal for four consecutive days. After irradiation, sperm morphology was observed, and sperm number was counted under microscope, and sperm apoptosis was detected by flow cytometry. Meanwhile, testis index was calculated, testicular morphology was observed using haematoxylin-eosin (HE) staining, and testicular ultrastructure was observed under transmission electron microscopy. The permeability of blood-testis barrier (BTB) was detected by Evans Blue fluorescence colorimetry. The protein levels of Bcl-2 associated X protein (Bax), B-cell leukemia-lymphoma-2 (Bcl-2) and Cleaved caspase 3, promyelocytic leukaemia zinc finger (PLZF) and c-kit proto-oncogene (c-kit) in testes were determined by western blotting (WB). The location of apoptotic cells was confirmed by terminal deoxynucleotidyl transferase (TdT) enzymaticated dUTP nick end labelling (TUNEL) assay. The levels of tumor necrosis factor alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by the biochemical assay kit. Compared with sham group, the sperm quality of mice in radiation group showed decreased number and survival rate, along with increased abnormality and total apoptosis rate. The testis index of irradiated mice was lower, the testicular apoptosis was increased, and their testicular histology and ultrastructure was severely damaged. The permeability of BTB was increased, the level of PLZF in testis was decreased, and the level of c-kit was increased by irradiation. After irradiation, the levels of TNF-α, TGF-β1, IL-10, T-SOD and MDA in testes were significantly changed. Taken together, abscopal effects of thoracic X-ray irradiation on spermatogenesis were obvious, which could decrease sperm quality and damage testicular morphology and increase the permeability of BTB, and a series of inflammation and oxidative stress factors were involved in the process. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation.
Despite extensive investigations in mammals and yeasts, the importance and specificity of COMPASS-like complex, which catalyzes histone 3 lysine 4 methylation (H3K4me), are not fully understood in ...plants. Here, we report that JMJ28, a Jumonji C domain-containing protein in Arabidopsis, recognizes specific DNA motifs through a plant-specific WRC domain and acts as an interacting factor to guide the chromatin targeting of ATX1/2-containing COMPASS-like complex. JMJ28 associates with COMPASS-like complex in vivo via direct interaction with RBL. The DNA-binding activity of JMJ28 is essential for both the targeting specificity of ATX1/2-COMPASS and the deposition of H3K4me at specific loci but exhibit functional redundancy with alternative COMPASS-like complexes at other loci. Finally, we demonstrate that JMJ28 is a negative regulator of plant immunity. In summary, our findings reveal a plant-specific recruitment mechanism of COMPASS-like complex. These findings help to gain deeper insights into the regulatory mechanism of COMPASS-like complex in plants.
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•JMJ28 recruits ATX1/2-COMPASS complex through interaction with the core component RBL•JMJ28-WRC domain recognizes specific DNA motif to confer target specificity of COMPASS•JMJ28 promotes H3K4me deposition and acts as a negative regulator of plant immunity
How COMPASS complex recognizes specific targets to implement H3K4 methylation is an important issue. Xie et al. report a chromatin-targeting mechanism of ATX1/2-COMPASS complex mediated by a JmjC protein JMJ28 through sequence-specific DNA binding in Arabidopsis. They show that the JMJ28-COMPASS module promotes H3K4 methylation and negatively regulates plant immunity.
Herein, the negative photoconductivity (NPC) effect has been observed in nanodiamonds (NDs) for the first time, and with illumination under a 660 nm laser lamp, the conductivity of the NDs decreases ...significantly. The NPC effect has been attributed to the trapping of carriers by the absorbed water molecules on the ND surfaces. A humidity sensor has been constructed based on the NPC effect of the NDs, and the sensitivity of the sensor can reach 106%, which is the highest value ever reported for carbon-based humidity sensors.
What makes free-hand sketches appealing for humans lies with its capability as a universal tool to depict the visual world. Such flexibility at human ease, however, introduces abstract renderings ...that pose unique challenges to computer vision models. In this paper, we propose a purpose-made sketch representation for human sketches. The key intuition is that such representation should be abstract at design, so to accommodate the abstract nature of sketches. This is achieved by interpreting sketch abstraction on two levels: appearance and structure. We abstract sketch structure as a pre-defined coarse-to-fine visual block hierarchy, and average visual features within each block to model appearance abstraction. We then discuss three general strategies on how to exploit feature synergy across different levels of this abstraction hierarchy. The superiority of explicitly abstracting sketch representation is empirically validated on a number of sketch analysis tasks, including sketch recognition, fine-grained sketch-based image retrieval, and generative sketch healing. Our simple design not only yields strong results on all said tasks, but also offers intuitive feature granularity control to tailor for various downstream tasks. Code will be made publicly available.
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