It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 ...matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8
T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.
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Density functional theory (DFT) calculations combined with “stochastic kicking” (SK) global search technique were performed to investigate the structural properties of EuSin-(1≤n≤13). ...It was found that the Eu atom in EuSin- preferred to occupy the surface position up to a size of 11Si atoms. However, starting fromn = 12, the endohedral structures were found, as depicted by the Eu atom inserting into the center of Si frame. The global minimum structures for each size was determined by comparing with the experimental photoelectron spectroscopy (PES). Natural population analysis (NPA) coupled with spin density isosurfaces were utilized to further investigate the electronic and magnetic properties of EuSin-. The observed magnetic moments significantly concentrates among the Eu atom, ascribed to the Eu 4f-electrons remaining largely as before encapsulating the Sin clusters. Meanwhile, the representative caged cluster EuSi12- was subjected to density of states (DOS) and HOMO-LUMO analysis, and the results showed a significant spin polarization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Polyhydroxyalkanoates (PHAs) are promising alternatives to petroleum-based plastics, owing to their biodegradability and superior material properties. Here, the controllable biosynthesis of ...scl-co-mcl PHA containing 3-hydroxybutyrate (3HB) and mcl 3-hydroxyalkanoates was achieved in Pseudomonas chlororaphis HT66. First, key genes involved in fatty acid β-oxidation, the de novo fatty acid biosynthesis pathway, and the phaC1-phaZ-phaC2 operon were deleted to develop a chassis strain. Subsequently, an acetoacetyl-CoA reductase gene phaB and a PHA synthase gene phaC with broad substrate specificity were heterologously expressed for producing and polymerizing the 3HB monomer with mcl 3-hydroxyalkanoates under the assistance of native β-ketothiolase gene phaA. Furthermore, the monomer composition of scl-co-mcl PHA was regulated by adjusting the amount of glucose and dodecanoic acid supplemented. Notably, the cell dry weight and scl-co-mcl PHA content reached 14.2 g/L and 60.1 wt %, respectively, when the engineered strain HT11Δ::phaCB was cultured in King’s B medium containing 5 g/L glucose and 5 g/L dodecanoic acid. These results demonstrated that P. chlororaphis can be a platform for producing scl-co-mcl PHA and has the potential for industrial application.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and Signal transducer and activator of ...transcription 3 (STAT3) have been implicated in the control of cellular metabolism, survival and growth. Our previous study has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA-mediated cellular EMT to affect breast cancer cell migration. Here we show that cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells. Importantly, MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box. Interestingly, miR-93-5p inhibits the EMT of breast cancer cells through suppressing the expression of MKL-1 and STAT3 via targeted their 3’UTR. These results demonstrated a novel pathway through which miR-93-5p regulates MKL-1 and STAT3 to affect EMT controlling breast cancer cell migration.
•Cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells.•Cooperativity of MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box.•MiR-93-5p inhibits the EMT of MCF-7 cells through suppressing MKL-1 and STAT3 via targeted their 3’UTR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Anthracnose caused by
is one of the most devastating fungal diseases of pepper (
L.). The utilization of chitin-binding proteins or chitinase genes is the best option to control this disease. A ...chitin-binding domain (CBD) has been shown to be crucial for the innate immunity of plants and activates the hypersensitive response (HR). The
chitinase gene has been identified and isolated from pepper plants.
has repeated CBDs that encode a chitinase enzyme that is transcriptionally stimulated by
infection. The knockdown of
in pepper plants confers increased hypersensitivity to
, resulting in its proliferation in infected leaves and an attenuation of the defense response genes
,
, and
in the
-silenced pepper plants. Additionally, H
O
accumulation, conductivity, proline biosynthesis, and root activity were distinctly reduced in
-silenced plants. Subcellular localization analyses indicated that the
protein is located in the plasma membrane and cytoplasm of plant cells. The transient expression of
increases the basal resistance to
by significantly expressing several defense response genes and the HR in pepper leaves, accompanied by an induction of H
O
biosynthesis. These findings demonstrate that
plays a prominent role in plant defense in response to pathogen infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of β-asarone, an active component from Chinese Herbs Acorus tatarinowii ...Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and β-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21. Also, the adult rats were exposed to Pb from embryo stage to 11 weeks old and β-asarone (2.5, 10, 40mg kg-1, respectively) was given from 9 to 11 weeks old. The level of β-asarone in brain tissue was measured by High Performance Liquid Chromatography. The Morris water maze test and Golgi-Cox staining method were used to assess spatial memory ability and synaptogenesis. The protein expression of NR2B subunit of NMDA receptor, Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and Wnt family member 7A (Wnt7a) in hippocampus, as well as mRNA expression of Arc/Arg3.1 and Wnt7a, was also explored. We found that β-asarone could pass through the blood brain barrier quickly. And β-asarone effectively attenuated Pb-induced reduction of spine density in hippocampal CA1 and dentate gyrus areas in a dose-dependent manner both in developmental and adult rats, meanwhile the Pb-induced impairments of learning and memory were partially rescued. In addition, β-asarone effectively up-regulated the protein expression of NR2B, Arc and Wnt7a, as well as the mRNA levels of Arc/Arg3.1 and Wnt7a, which had been suppressed by Pb exposure. The results suggest the neuroprotective properties of β-asarone against Pb-induced memory impairments, and the effect is possibly through the regulation of synaptogenesis, which is mediated via Arc/Arg3.1 and Wnt pathway.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs‐derived exosomes in ...microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)‐exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT‐qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis‐related proteins, oxidative stress, and angiogenic activity using CCK‐8, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in vivo. Our study found that HBMVECs‐Exos reduced M2 markers (IL‐10, CD163, and CD206), increased M1 markers (TNF‐α, IL‐1β, and IL‐12), CD86‐positive cells, and inflammatory cytokines (TNF‐α and IL‐1β), indicating the promotion of microglial M1‐polarization. Microglial M1‐polarization induced by HBMVECs‐Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs‐Exos‐induced alterations. Mechanistically, circ_0000495 adsorbed miR‐579‐3p to upregulate toll‐like receptor 4 (TLR4) in microglia; miR‐579‐3p suppressed HBMVECs‐Exos‐induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in vivo via activating TLR4/nuclear factor‐κB (NF‐κB) pathway. Collectively, OGD‐treated HBMVECs‐Exos transmitted circ_0000495 to regulate miR‐579‐3p/TLR4/NF‐κB axis in microglia, thereby facilitating microglial M1‐polarization and endothelial cell damage.
In OGD‐subjected BMVECs, the upregulated YY1 transcriptionally activated circ_0000495, then circ_0000495 was transported by exosomes to microglial cells. In microglial cells, circ_0000495 targeted miR‐579‐3p to upregulate TLR4, leading to M1 microglial polarization, which in turn promoted apoptosis and inhibited angiogenesis of BMVECs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) remains one of the most refractory malignancies worldwide. Schlafen family member 11 (SLFN11) has been reported to play an important role in inhibiting the production ...of human immunodeficiency virus 1 (HIV-1). However, whether SLFN11 also inhibits hepatitis B virus (HBV), and affects HBV-induced HCC remain to be systematically investigated.
qRT-PCR, western blot and immunohistochemical (IHC) staining were conducted to investigate the potential role and prognostic value of SLFN11 in HCC. Then SLFN11 was stably overexpressed or knocked down in HCC cell lines. To further explore the potential biological function of SLFN11 in HCC, cell counting kit-8 (CCK-8) assays, colony formation assays, wound healing assays and transwell cell migration and invasion assays were performed
. Meanwhile, HCC subcutaneous xenograft tumor models were established for
assays. Subsequently, immunoprecipitation (IP) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analyses were applied to understand the molecular mechanisms of SLFN11 in HCC. Co-IP, immunofluorescence and IHC staining were used to analyze the relationship between ribosomal protein S4 X-linked (RPS4X) and SLFN11. Finally, the therapeutic potential of SLFN11 with mTOR pathway inhibitor INK128 on inhibiting HCC growth and metastasis was evaluated
and
orthotopic xenograft mouse models.
We demonstrate that SLFN11 expression is decreased in HCC, which is associated with shorter overall survival and higher recurrence rates in patients. In addition, we show that low SLFN11 expression is associated with aggressive clinicopathologic characteristics. Moreover, overexpression of SLFN11 inhibits HCC cell proliferation, migration, and invasion, facilitates apoptosis
and impedes HCC growth and metastasis
all of which are attenuated by SLFN11 knockdown. Mechanistically, SLFN11 physically associates with RPS4X and blocks the mTOR signaling pathway. In orthotopic mouse models, overexpression of SLFN11 or inhibition of mTOR pathway inhibitor by INK128 reverses HCC progression and metastasis.
SLFN11 may serve as a powerful prognostic biomarker and putative tumor suppressor by suppressing the mTOR signaling pathway via RPS4X in HCC. Our study may therefore offer a novel therapeutic strategy for treating HCC patients with the mTOR pathway inhibitor INK128.
This randomized controlled study investigated the feasibility of early ambulation after liver resection and the effect of the amount of activity on postoperative recovery.
A total of 120 patients who ...underwent liver resection were randomly divided into two groups for the comparative analysis of the following factors: amount of activity, pain control, sleeping state, perioperative gastrointestinal function recovery, incidence of complications and postoperative hospital stay.
Compared with the control group, patients undergoing liver resection performing early postoperative ambulation had faster gastrointestinal function recovery (First exhaust time 2.2 ± 1.4 vs. 3.3 ± 2.3 p < 0.01; First flatus time 2.3 ± 1.7 vs. 3.1 ± 2.5 p = 0.04) and shorter postoperative hospital stays (6.6 ± 2.3 vs. 7.7 ± 2.1 p = 0.01), with statistically significant differences. There was no significant difference in the incidence of postoperative complications between the two groups (p > 0.05).
Early ambulation after liver resection is safe and feasible. It can reduce the patient's pain and economic burden, increase the patient's comfort, reduce the nursing workload, achieve rapid recovery, and improve patient satisfaction.
•Quantitative study on early enforced mobilization for ERAS of liver resection.•Early enforced mobilization after liver resection is safe and feasible.•Wireless smart wristband available for clinical observation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro ...acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV.
A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 μg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated.
Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells.
Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.
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