Interleukin-6 is an inflammatory cytokine with wide-ranging biological effects. It has been widely demonstrated that neuroinflammation plays a critical role in the development of pathological pain. ...Recently, various pathological pain models have shown elevated expression levels of interleukin-6 and its receptor in the spinal cord and dorsal root ganglia. Additionally, the administration of interleukin-6 could cause mechanical allodynia and thermal hyperalgesia, and an intrathecal injection of anti-interleukin-6 neutralizing antibody alleviated these pain-related behaviors. These studies indicated a pivotal role of interleukin-6 in pathological pain. In this review, we summarize the recent progress in understanding the roles and mechanisms of interleukin-6 in mediating pathological pain associated with bone cancer, peripheral nerve injury, spinal cord injury, chemotherapy-induced peripheral neuropathy, complete Freund's adjuvant injection, and carrageenan injection. Understanding and regulating interleukin-6 could be an interesting lead to novel therapeutic strategies for pathological pain.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recently, the advancement of cognitive computing and three-way decisions has enabled in-depth sequential pattern understanding through temporal association analysis. The main challenge is to obtain ...concise patterns that express richer semantics for multivariate time series (MTS) analysis. In this paper, we propose a tri-partition state alphabet-based sequential pattern (Tri-SASP) for MTSs. First, a tri-wildcard gap inserted between each pair of adjacent states enhances the flexibility of the method. Second, a given set of states is partitioned into positive (POS), negative (NEG) and boundary (BND) regions. The states in POS can only be used to construct a Tri-SASP, the states in NEG can only be matched by a tri-wildcard gap, and the states in BND can be used in both ways. Finally, horizontal and vertical algorithms are proposed to obtain frequent Tri-SASPs in a breadth-first manner. The experimental results on four real-world datasets show that (1) the discovered Tri-SASPs and temporal rules can enrich human cognition; (2) the two tri-partition strategies can bring us very meaningful and varied Tri-SASPs; and (3) the two algorithms are effective and scalable.
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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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•A novel Fe3O4@Zn2Al-LDH@MIL-53(Al) was synthesized by a facile two-step process.•The material was used for the removal of azole fungicides from environmental water.•The equilibrium ...was reaching within 5 min with high adsorption capacity.•The mechanisms were including hydrogen-bonding interaction and π–π interaction.
In this work, a novel Fe3O4@ZnAl-LDH@MIL-53(Al) composite was synthesized by a facile three-step process and utilized as an adsorbent for the removal of azole fungicides from environmental water. The characterization results revealed that double hydroxide (ZnAl-LDH) and metal organic framework (MIL-53) have been successfully tethered to the shell of Fe3O4. The main factors affecting the removal efficiencies were investigated, and results revealed that Fe3O4@ZnAl-LDH@MIL-53(Al) composite possessed high removal efficiencies for azole fungicides. Furthermore, the adsorption mechanism was investigated and including hydrogen-bonding interaction, chemisorption and π–π interaction. The adsorption kinetic was more consistent with the pseudo-second-order kinetic model, and the whole adsorption process could reach the equilibrium within 5 min. Langmuir adsorption isotherm model could describe the adsorption process most accurately, and the maximum adsorption values of azole fungicides were in the range of 43.54–71.79 mg g−1. Meanwhile, the adsorption thermodynamics indicated that the adsorption process was exothermic and spontaneous. Hence, Fe3O4@ZnAl-LDH@MIL-53(Al) composite had a great application potential in the removal of azole fungicides from the environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Highly efficient gene delivery systems are essential for genetic engineering in plants. Traditional delivery methods have been widely used, such as Agrobacterium-mediated transformation, polyethylene ...glycol (PEG)-mediated delivery, biolistic particle bombardment, and viral transfection. However, genotype dependence and other drawbacks of these techniques limit the application of genetic engineering, particularly genome editing in many crop plants. There is a great need to develop newer gene delivery vectors or methods. Recently, nanomaterials such as mesoporous silica particles (MSNs), AuNPs, carbon nanotubes (CNTs), and layer double hydroxides (LDHs), have emerged as promising vectors for the delivery of genome engineering tools (DNA, RNA, proteins, and RNPs) to plants in a species-independent manner with high efficiency. Some exciting results have been reported, such as the successful delivery of cargo genes into plants and the generation of genome stable transgenic cotton and maize plants, which have provided some new routines for genome engineering in plants. Thus, in this review, we summarized recent progress in the utilization of nanomaterials for plant genetic transformation and discussed the advantages and limitations of different methods. Furthermore, we emphasized the advantages and potential broad applications of nanomaterials in plant genome editing, which provides guidance for future applications of nanomaterials in plant genetic engineering and crop breeding.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cadmium (Cd) and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not entirely understood yet. Aberrant methylation was investigated in order to ...obtain insight into the DNA repair-related epigenetic mechanisms underlying CdCl2-induced malignant transformation of human bronchial epithelial cells (16HBE). Gene expression and DNA methylation were assessed in untreated control cells; 5th, 15th, and 35th passage of CdCl2-treated cells and tumorigenic cells (TCs) from nude mice by using high-performance liquid chromatography, real-time PCR, Western blot analysis, and methylation-specific PCR assay. During Cd-induced malignant transformation, global DNA methylation progressively increased and was associated with the overexpression of the DNA methyltransferase genes DNMT1 and DNMT3a but not DNMT3b. Expression of both the messenger RNA and proteins of the DNA repair genes (hMSH2, ERCC1, XRCC1, and hOGG1) progressively reduced and DNA damage increased with Cd-induced transformation. The promoter regions of hMSH2, ERCC1, XRCC1, and hOGG1 were heavily methylated in the 35th passage transformed cells and the TCs. The DNA demethylating agent 5-aza-2′-deoxycytidine could reverse the Cd-induced global DNA hypermethylation, DNMT hyperactivity, and the silencing of hMSH2, ERCC1, XRCC1, and hOGG1 in a time-dependent manner. The results indicate that DNMT1 and DNMT3a overexpression can result in global DNA hypermethylation and silencing of the hMSH2, ERCC1, XRCC1, and hOGG1 genes. They may partly explain the epigenetic mechanisms underlying the carcinogenesis due to Cd.
Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely ...high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Cancer-induced bone pain (CIBP) treatment remains a clinical challenge because the pathophysiological mechanisms are not fully understood. Recently, it was verified that shifting microglial ...polarization toward the M2 phenotype reveals a potential strategy for CIBP treatment. Naringenin, a natural flavone flavonoid, has been reported to have antioxidant, anti-inflammatory and neuroprotective properties. However, the role of naringenin on regulating microglial polarization in CIBP rats and the molecular mechanisms participating in this process have not been fully clarified. Herein, we investigated the potential effect of naringenin on M1/M2 microglial polarization and further explored the potential mechanisms of this action. Our study demonstrated that intraperitoneal administration of naringenin could upregulate the antioxidative molecule glutathione peroxidase 4 (GPx4) level in the spinal cord, as well as bone cancer-induced mechanical allodynia in rats. Moreover, naringenin treatment also suppressed microglia-mediated neuroinflammation by downregulating the phosphorylation of nuclear factor κB (NF-κB) p65 expression and promoting microglial polarization toward the M2 phenotype in CIBP rats. The promoting effects mediated by naringenin on M1/M2 microglial polarization are dependent on the serine/threonine protein kinase adenosine monophosphate-activated protein kinase (AMPK)/proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling pathway. Inhibition of AMPK activation with the classical AMPK inhibitor Compound C attenuated this effect of naringenin. These results improved the understanding of the anti-inflammatory property of naringenin on microglial polarization, which might provide new alternative avenues for CIBP treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The attributes of good solubility and the redox-neutral nature of molten salt fluxes enable them to be useful for the synthesis of novel crystalline actinide compounds. In this work, a flux growth ...method under an inert atmosphere is proposed to explore the valence diversity of uranium, and a series of five uranium silicate structures, K3Cl(UVIO2)(Si4O10) (1), Cs3(UVO2)(Si4O10) (2), K2UIV(Si2O7) (3), K8(UVIO2)(UVO2)2(Si8O22) (4), and Cs6UIV(UVO)2(Si12O32) (5), were synthesized using different metal halide salt and feeding U/Si ratios. Crystal structure analysis reveals that the utilization of argon atmosphere that helps to avoid possible oxidation of low-valence uranium generates a variety of oxidation states of uranium including U(VI), U(V), U(IV), mixed-valence U(V) and U(VI), and mixed-valence U(IV) and U(V). Characterization of physicochemical properties of representative compounds shows that all these uranium silicate compounds have bandgaps among the range of 2.0–3.4 eV, and mixed-valence uranium silicate compounds have relatively narrower bandgaps. Density functional theory calculations on formation enthalpies, lattice energies, and bandgaps of all five compounds were also performed to provide more structural information about these uranium silicates. This work enriches the library of variable-valence uranium silicate compounds and provides a feasible way to produce novel actinide compounds with intriguing properties through the flux growth method that might show potential application in relevant fields such as storage media for nuclear waste.
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IJS, KILJ, NUK, PNG, UL, UM
Its high coordination number and tendency to cluster make Th4+ suitable for constructing metal–organic frameworks (MOFs) with novel topologies. In this work, two novel thorium-based heterometallic ...MOF isomers (IHEP-17 and IHEP-18) were assembled from a Th6 cluster, a multifunctional organic ligand 4-(1H-pyrazol-4-yl)benzoic acid (HPyba), and Cu2+/Ni2+ cations via the one-pot solvothermal synthesis strategy. The framework features a 6,12-connected new topology net and contains two kinds of supramolecular cage structures, Th36M4 and Th24M2, suitable for guest exchange. Both MOF materials can efficiently adsorb I2. X-ray photoelectron spectroscopy, Raman spectroscopy, and single-crystal X-ray diffraction indicate that the adsorbed iodine is uniformly distributed within the Th36M4 cage but not the Th24M2 cage in the form of I3 –.
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IJS, KILJ, NUK, PNG, UL, UM
Rationalizing the use of depleted uranium resources has always been of great interest. Herein, we have obtained two actinide compounds by regulating the ratio of each component in the crystal growth ...process. By modulating the coordination microenvironment of uranyl, the actinide compounds exhibited significant differences in photocatalytic CO2 reduction performance. The photocatalytic CO2 reduction by UCu2 exhibited excellent reactivity, and the CO generation rate reached 481.6 μmol g−1 h−1. This study provides a reference and support for the rational application of depleted uranium resources and the application of coordinated polymers in the field of photocatalytic CO2 reduction.
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