The deubiquitinase otubain 2 (OTUB2) has been reported to play significant roles in the tumorigenesis of several cancers, but the role of OTUB2 in liver cancer is not investigated yet. In the present ...study, OTUB2 was found significantly upregulated in liver cancer tumor tissues and cell lines, and elevated OTUB2 indicated as a negative index for the overall survival of liver cancer patients. At the cellular level, knockdown of OTUB2 markedly inhibited liver cancer cell growth. Our further investigations revealed that knockdown of OTUB2 significantly suppressed NF‐κB‐driving luciferase activity, and markedly inhibited the phosphorylation of NF‐κB p65 in liver cancer cells, which indicated that OTUB2 mediated liver cancer cell growth by regulating NF‐κB signaling. Additionally, we found that liver cancer cell lines harboring higher OTUB2 expression were more sensitive to NF‐κB inhibitors, and overexpression of OTUB2 could significantly reduce the antitumor effects of NF‐κB inhibitors in liver cancer cells. This study indicated that OTUB2 could be a promising target for the treatment of liver cancer in the future.
Oxidase‐mimicking nanozymes are more desirable than peroxidase‐mimicking ones since H2O2 can be omitted. However, only a few nanomaterials are known for oxidase‐like activities. In this work, we ...compared the activity of Mn2O3, Mn3O4 and MnO2 and found that Mn2O3 had the highest oxidase activity. Interestingly, the activity of Mn2O3 was even inhibited by H2O2. The oxidase‐like activity of Mn2O3 was not much affected by the presence of proteins such as bovine serum albumin (BSA), but the physisorption of antibodies to Mn2O3 was not strong enough to withstand the displacement by BSA. We then treated Mn2O3 with 3‐aminopropyltriethoxysilane to graft an amine group, which was used to conjugate antibodies using glutaraldehyde as a crosslinker. A one‐step indirect competitive ELISA (icELISA) was developed for the detection of isocarbophos, and an IC50 of 261.7 ng/mL was obtained, comparable with the results of the standard two‐step assay using horseradish peroxidase (HRP)‐labeled antibodies. This assay has the advantage of significant timesaving for rapid detection of large amounts of samples. This work has discovered a highly efficient oxidase‐mimicking nanozyme useful for various nano‐ and analytical applications.
Mn2O3 nanoparticles have the highest oxidase‐like activity among the tested metal oxides, but the activity is inhibited by H2O2. Mn3O4 behaves similarly, while the activity of MnO2 is enhanced by H2O2.
We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment ...indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets,
N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.
The studies of topological phases of matter have been developed from condensed matter physics to photonic systems, resulting in fascinating designs of robust photonic devices. Recently, higher-order ...topological insulators have been investigated as a novel topological phase of matter beyond the conventional bulk-boundary correspondence. Previous studies of higher-order topological insulators have been mainly focused on the topological multipole systems with negative coupling between lattice sites. Here we experimentally demonstrate that second-order topological insulating phases without negative coupling can be realized in two-dimensional dielectric photonic crystals. We visualize both one-dimensional topological edge states and zero-dimensional topological corner states by using the near-field scanning technique. Our findings open new research frontiers for photonic topological phases and provide a new mechanism for light manipulating in a hierarchical way.
•National ecosystem service values (ESV) are still insufficiently well evaluated in China.•A modified equivalent factor method was utilized to evaluate the spatial-temporal variation of ESV.•Forest ...provided the highest value; regulating services the highest contribution.•ESV varied seasonally and spatially.•Ecological planning should consider the ESV provided by ecosystems.
This study initiated a dynamic assessment method of ecosystem service values (ESV), based on an analogy with the labor theory of value, by modifying and developing the method of equivalence factor per unit area. Using such method, the monthly values from 11 categories of ecosystem services provided by China’s ecosystems in 2010 were dynamically estimated. The results indicated that (1) a total ESV of 5.63 trillion US dollars annually was provided, of which forests provided the highest proportion (46.0%), and the regulating services had the highest contribution among the four categories of services (71.3%); (2) the total ESV from 11 categories showed apparent seasonal variation, with higher values from May to September than from November to February which contributed 76.9% and 7.4% to total ESV, respectively; (3) the highest ESV per unit area mainly distributed in southern and eastern areas, and the value generally decreased from southeast to northwest; and (4) the ratio of ESV per capita to the gloss domestic product (GDP) per capita was about 0.87, and such ratio was lowest in the most economically developed and densely populated areas. Therefore, the dynamic assessment method developed in this study can provide a scientific basis for Chinese policy decision-making.
Many types of mammalian cells can aggregate and differentiate into 3‐D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, ...multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.
Lactate is a prominent energy substrate for oxidative tumor cells. Interfering with the lactate‐fueled respiration of oxidative tumor cells would be a promising therapeutic strategy for cancer ...treatment. In this study, α‐cyano‐4‐hydroxycinnamate (CHC) is incorporated into a porous Zr (IV)‐based porphyrinic metal‐organic framework (PZM) nanoparticle, to reduce the lactate uptake by inhibiting the expression of lactate‐proton symporter, monocarboxylate transporter 1 (MCT1) in tumor cells, thus transform lactate‐fueled aerobic respiration to anaerobic glycolysis. The alteration in energy supply can also decrease the oxygen consumption in tumor cells, which would facilitate the photodynamic therapy (PDT) in cancer treatment. Moreover, hyaluronic acid (HA) is coated on the surface of PZM nanoparticles for CD44‐targeting and hyaluronidase‐induced intracellular drug releasing. Both in vitro and in vivo studies confirmed good biocompatibility and enhanced PDT efficacy of the HA‐coated PZM nanoparticles (CHC‐PZM@HA) in tumor cells. The CHC‐PZM@HA platform will provide a new perspective in cancer therapy.
Enhanced photodynamic therapy (PDT) by inhibiting lactate uptake. Hyaluronic acid modified porphyrinic metal‐organic framework nanoparticles delivered MCT1 inhibitor into cancer cells. With the releasing of loaded drugs by enzymatic degradation, the aerobic respiration of lactate is disturbed and intratumoral oxygen pressure is upregulated. The nanocarrier system significant enhances the anticancer effect of PDT.
Helical nanographenes with high quantum yields and strong chiroptical responses are pivotal for developing circularly polarized luminescence (CPL) materials. Here, we present the successful synthesis ...of novel π‐extended double 7helicenes (ED7Hs) where two helicene units are fused at the meta‐ or para‐position of the middle benzene ring, respectively, as the structural isomers of the reported ortho‐fused ED7H. The structural geometry of these ED7Hs is clearly characterized by single‐crystal X‐ray analysis. Notably, this class of ED7Hs exhibits bright luminescence with high quantum yields exceeding 40 %. Through geometric regulation of two embedded 7helicene units from ortho‐, meta‐ to para‐position, these ED7Hs display exceptional amplification in chiroptical responses. This enhancement is evident in a remarkable approximate fivefold increase in the absorbance and luminescence dissymmetry factors (gabs and glum), respectively, along with a boosted CPL brightness up to 176 M−1 cm−1, surpassing the performance of most helicene‐based chiral NGs. Furthermore, DFT calculations elucidate that the geometric adjustment of two 7helicene units allows the precise alignment of electric and magnetic transition dipole moments, leading to the observed enhancement of their chiroptical responses. This study offers an effective strategy for magnifying the CPL performance in chiral NGs, promoting their expanded application as CPL emitters.
π‐Extended helical nanographenes (ED7Hs) have been synthesized where the two embedded 7helicene units are fused at the ortho‐, meta‐ or para‐position of the middle benzene ring, respectively. The obtained ED7Hs display exceptional fivefold amplification in chiroptical responses with enhanced circularly polarized luminescence (CPL) brightness up to 176 M−1 cm−1.
Food consumption acts as an intermediary that connects ecosystems with human systems in grassland areas. In this study, we used fuzzy cognitive mapping to quantitatively assess the factors that ...affect food consumption in the Xilin Gol Grassland, China, from the perspective of local rural households. We found that household perceptions of the factors that affect food consumption differed among parts of the grassland transects in both the number and the strength of these factors. Livestock numbers, household income, regional economic development, consumption habits, age, and infrastructure were the most important factors mentioned by the farmers and herders, but herders were more sensitive to ecological and economic factors, whereas farmers focused more on personal and social factors. The differences in the main factors between study areas revealed the key economic, social, and ecological dimensions. Our results provide a reference for policymakers to develop improved policies to encourage regional sustainable development.
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Researches are urgently needed on its molecular pathogenesis and biological ...characteristics. Metabolic reprogramming for adaptation to the tumour microenvironment (TME) has been recognized as a hallmark of cancer. Dysregulation of lipid metabolism especially fatty acid (FA) metabolism, which involved in the alternations of the expression and activity of lipid‐metabolizing enzymes, is a hotspot in recent study, and it may be involved in HCC development and progression. Meanwhile, immune cells are also known as key players in the HCC microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells in TME are closely related to abnormal lipid metabolism. In this review, we summarize the recent findings of lipid metabolic reprogramming in TME and relate these findings to HCC progression. Our understanding of dysregulated lipid metabolism and associated signalling pathways may suggest a novel strategy to treat HCC by reprogramming cell lipid metabolism or modulating TME.
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