Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed ...N-(3-(5,7-dimethylbenzo doxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Technological advancements have led to an increase in the popularity of consumer-to-consumer product trading (C2C-PT). How C2C-PT affects the manufacturer (called the "firm") and consumers in the ...market is unclear. We, therefore, build analytical models to explore this problem. We consider a case in which a firm develops and sells a product to consumers in the market. Consumers possess heterogeneous random valuations of the product and are strategic in the sense that they are forward-looking utility maximizers. The firm makes the optimal decision on the product selling price. We study the impacts of C2C-PT on both the firm and consumers. We identify the optimal purchasing decision for the consumers and establish the optimal pricing policy for the firm. We show that the presence of C2C-PT may either benefit or hurt the firm and consumers, while the consumer's strategic behavior will always bring harm to the firm. Most interestingly, we prove that strategic purchasing behavior is not always beneficial to consumers themselves.
Alzheimer’s disease (AD) represents a progressive neurodegenerative disorder characterized by distinctive neuropathological changes. Recently, long noncoding RNAs (lncRNAs) have become a key area of ...interest due to their potential in AD therapy. Hence, the aim of the current study was to investigate the effect of lncRNA SOX21-AS1 on neuronal oxidative stress injury in mice with AD via the Wnt signaling pathway by targeting FZD3/5. Microarray analysis was performed to screen AD-related differentially expressed genes (DEGs). Following verification of the target relationship between SOX21-AS1 and FZD3/5, the contents of OH
−
, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined, with the expressions of SOX21-AS1, FZD3/5, β-catenin, cyclin D1, and 4-HNE in hippocampal neuron cells subsequently detected. Cell cycle distribution and apoptosis were evaluated. Bioinformatics analysis revealed that SOX21-AS1 was upregulated in AD, while highlighting the co-expression of SOX21-AS1 and FZD3/5 genes and their involvement in the Wnt signaling pathway. AD mice exhibited diminished memory and learning ability, increased rates of MDA, OH
−
, SOX21-AS1, 4-HNE, and elevated levels of hippocampal neuron cell apoptosis, accompanied by decreased levels of SOD, CAT, GSH-Px, FZD3/5, β-catenin, and cyclin D1. Silencing of SOX21-AS1 resulted in decreased OH
−
, MDA contents, SOX21-AS1, and 4-HNE, and increased SOD, CAT, GSH-Px, FZD3/5, β-catenin, and cyclin D1, as well as reduced apoptosis of hippocampal neuron cells. Taken together, the key findings of the present study demonstrated that silencing of lncRNA SOX21-AS1 could act to alleviate neuronal oxidative stress and suppress neuronal apoptosis in AD mice through the upregulation of FZD3/5 and subsequent activation of the Wnt signaling pathway.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus‐induced cell migration facilitates viral transmission. ...However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi‐omics analyses and high‐resolution live‐cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial–mesenchymal transition‐like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV‐hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading‐edge protrusion formation, and the rear‐edge recontraction, which coordinates VACV‐induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
We have conducted a systematic line survey, primarily focused on transitions of the methanol and ammonia molecules, and monitoring observations of masers toward the high-mass star-forming ...region NGC 6334I. These observations were undertaken between 2019 and 2022 in the
C, K, Ka
, and
Q
bands with the Tianma Radio Telescope. In total, 63 CH
3
OH (including 11 class I and nine class II maser or maser candidate), 18
13
CH
3
OH, and 34 NH
3
(including seven maser or maser candidate) transitions were detected. The emission is likely associated with the luminosity outburst source MM1. Rotation diagram analysis of multiple ammonia transitions shows that the gas temperature in the molecular core was a factor of 2 higher than that measured in previous observations in the pre-burst stage. This suggests that the molecular core has likely been heated by radiation originating from the luminosity outburst. Maser variability in the methanol and excited-state OH masers shows a general trend that the maser components associated with the luminosity outburst have decreased in their intensity since 2020. The decay in the maser luminosity indicates that the outburst is possibly declining, and as a result, the duration of the MM1 luminosity outburst may be shorter than the predicted 40 yr duration. Compared to the masers detected toward another luminosity outburst source, G358.93-0.03, abundant class I methanol masers and strong water maser flares were also detected toward NGC 633I, but masers from rare class II methanol transitions and new molecules were absent toward NGC 6334I. The large number of detections of maser transitions toward the two burst sources provided a database for further maser modeling to explore the physical environments associated with accretion burst events.
Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State ...Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Being able to balance between high catalytic activity and good stability under elevated reaction temperature is a great challenge for dry reforming of methane over nickel-based catalysts. In this ...work, two strategies including bimetallic formation and metal restriction over defects of hexagon boron nitride are combined. The integration of urea-based exfoliation technique with a consecutive solution combustion method employing urea as fuel is demonstrated over boron nitride supported catalysts. Anchoring of NiCo alloy onto defective hexagonal boron nitride nanosheet could enhance carbon removal significantly. The defective h-BN support with its promising basicity improves CO2 adsorption on catalysts’ surface, hence facilitates elimination of inactive carbon species. As a result, the catalyst exhibits high catalytic activity with 83.9% and 90.3% conversion for CH4 and CO2, respectively, and keep 100% retention during 130 h of reaction time at 750 °C. This work provides an alternative to develop high-performance catalysts for dry reforming of methane.
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•NiCo catalysts over defective boron nitride nanosheets were prepared.•Boron nitride nanosheets facilitated highly dispersed bimetallic site formation.•Cooperation of Co could enhance tolerance towards carbon formation of Ni.•NiCo catalysts over boron nitride for dry reforming of methane were demonstrated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant ...tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Osteoarthritis (OA) is a chronic degenerative disease of the bone and joints. Immune-related genes and immune cell infiltration are important in OA development. We analyzed immune-related genes and ...immune infiltrates to identify OA diagnostic markers. The datasets GSE51588, GSE55235, GSE55457, GSE82107, and GSE114007 were downloaded from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and differentially expressed immune-related genes (DEIRGs), and functional correlation analysis was conducted. Second, CIBERSORT was used to evaluate infiltration of immune cells in OA tissue. Finally, the least absolute shrinkage and selection operator logistic regression algorithm and support vector machine-recurrent feature elimination algorithm were used to screen and verify diagnostic markers of OA. A total of 711 DEGs and 270 DEIRGs were identified in this study. Functional enrichment analysis showed that the DEGs and DEIRGs are closely related to cellular calcium ion homeostasis, ion channel complexes, chemokine signaling pathways, and JAK-STAT signaling pathways. Differential analysis of immune cell infiltration showed that M1 macrophage infiltration was increased but that mast cell and neutrophil infiltration were decreased in OA samples. The machine learning algorithm cross-identified 15 biomarkers (BTC, PSMD8, TLR3, IL7, APOD, CIITA, IFIH1, CDC42, FGF9, TNFAIP3, CX3CR1, ERAP2, SEMA3D, MPO, and plasma cells). According to pass validation, all 15 biomarkers had high diagnostic efficacy (AUC > 0.7), and the diagnostic efficiency was higher when the 15 biomarkers were fitted into one variable (AUC = 0.758). We developed 15 biomarkers for OA diagnosis. The findings provide a new understanding of the molecular mechanism of OA from the perspective of immunology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment ...of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-β1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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