RING finger protein 168 (RNF168) is an E3 ubiquitin ligase with the RING finger domain. It is an important protein contributing to the DNA double-strand damage repair pathway. Recent studies have ...found that RNF168 is significantly implicated in the occurrence and development of various cancers. Additionally, RNF168 contributes to the drug resistance of tumor cells by enhancing their DNA repair ability or regulating the degradation of target proteins. This paper summarizes and prospects the research progress of the structure and main functions of RNF168, especially its roles and the underlying mechanisms in tumorigenesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bayesian methodology is a good way to infer unknown parameters in a marine environment. A passive source location method in a shallow water waveguide with a single sensor based on Bayesian theory is ...presented in this paper. The input of a Bayesian inversion algorithm is received different normal mode impulse signals, which are separated and extracted with a warping transformation from received broadband impulse signals. The source range, depth, and other seabed parameters were estimated without prior knowledge of the seabed information. Different normal mode impulse acoustic signals travelling at different group speeds arrived at the sensor at different times because of the dispersion characteristics of the shallow water waveguide. The time delay of different modes can be used for the passive source location. However, normal mode group speeds are greatly affected by the environmental parameters. The performance of the passive location becomes negative when parameters mismatch. In this paper, the source location was transformed to the inversion of the source location and environmental parameters, which can be estimated accurately based on the multi-dimensional posterior probability density (PPD). This method is less limited by environmental factors, and the accuracy of inversion results can be analyzed according to the PPD of inversion parameters, which has higher reliability and a wider application scope. The effectiveness and robustness of the algorithm were quantified in terms of the root mean squared error (RMSE) at a variety of signal-to-noise ratios (SNRs) in 50 simulation sets. The RMSE values decreased with the SNR. The validity and accuracy of the method were proved by the results of simulation and experiment data.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A tunable multiband terahertz metamaterial absorber, based on vanadium dioxide (VO
), is demonstrated. The absorber comprises a three-layer metal-insulator-metal (MIM) configuration with a split ring ...and slots of VO
on the uppermost layer, a middle dielectric substrate based on silicon dioxide (SiO
), and a gold reflector on the back. The simulation results indicate that, when VO
is in the metallic state, the proposed metamaterial exhibits nearly perfect absorption at six distinct frequencies. The design achieves an average absorption of 98.2%. The absorptivity of the metamaterial can be dynamically tuned from 4% to 100% by varying the temperature-controlled conductivity of VO
. The proposed metamaterial absorber exhibits the advantages of polarization insensitivity and maintains its absorption over 80% under different incident angle conditions. The underlying physical mechanism of absorption is explained through impedance matching theory, interference theory, and the distribution of electric fields. The ability to achieve multiband absorption with tunable characteristics makes the proposed absorber a promising candidate for applications in terahertz sensing, imaging, communication, and detection. The polarization insensitivity further enhances its practicality in various scenarios, allowing for versatile and reliable performance in terahertz systems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), has drawn attentions for its function in alleviating radiation damage. However, the detailed mechanisms of Ilomastat's ...protection from animal model remain not fully clear. In this study, the C57BL/6 mice were pre-administrated with Ilomastat or vihicle for 2 h, and then total body of mice were exposed to 6 Gy of γ-rays. The protective effect of Ilomastat on the hematopoietic system in the irradiated mice were investigated. We found that pretreatment with Ilomastat significantly reduced the level of TGF-β1 and TNF-α, and elevated the number of bone marrow (BM) mononuclear cells in the irradiated mice. Ilomastat pretreatment also increased the fraction of BM hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) at day 30 after irradiation, and protected the spleen of mouse from irradiation. These results suggest that Ilomastat promotes the recovery of hematopoietic injury in the irradiated mice, and thus contributes to the survival of mouse after irradiation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, which is caused by a disorder in bone metabolism due to excessive activation of osteoclasts. Bushen ...Huoxue decoction (BHD) is an herbal formula with multiple pharmacological effects, including anti-inflammatory, antioxidant activity and stem cell migration promotion. However, the effect of BHD on osteoclastogenesis has not been reported. In this study, we aimed to elucidate the effect of BHD on RANKL-stimulated osteoclastogenesis and explored its underlying mechanisms of action
. Our results show that BHD had no effect on BMMs and RAW264.7 cells viability, but inhibited RANKL-induced osteoclast formation
. Furthermore, BHD attenuated RANKL-induced NF-κB, ERK, and JNK signaling. The attenuation of NF-κB, ERK, and JNK activation were enough to impede downstream expression of c-fos and NFATc1 and related specific genes. Meanwhile, we investigated the therapeutic effect of BHD on glucocorticoid-induced osteoporosis (GIOP) mice. The result indicated that BHD prevents glucocorticoid-induced osteoporosis and preserves bone volume by repressing osteoclast activity. Collectively, BHD shows significant osteoclast inhibition and holds great promise in the treatment of osteoporosis.
Diabetic nephropathy (DN) is a common disease, and patients often do not have satisfactory treatments. We investigated therapeutic effects of Fuxin Granules(FX) on DN and potential molecular ...mechanisms. We orally administered doses of FX to db/db mice for 10 weeks and measured total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol. H&E, PAS, Masson, and Oil Red O staining were used to observe the structure of kidneys and calculate indices of kidney function. We used pharmacological analysis to investigate potential mechanisms of FX. Relative mRNA and protein levels in the TGF-β1/Smad, TGF-β1/Smad, and VEGF/VEGFR2 pathways were examined. TC, TG, and LDL-C were markedly reduced, lipid accumulation was low, fibrosis reduced, kidney atrophy improved, kidney lipid droplet number significantly reduced, and glomerular filtration function improved by FX treatment. Multi-channel therapeutic effects in DN through the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways occurred, and FX substantially reduced expression of TGF-β1 in the glomeruli. FX significantly inhibited TGF-β1, Smad2/3 total protein levels, Smad2/3 phosphorylation mRNA levels of TGF-β1, Smad2, and Smad3. eNOS, VEGFA, and VEGFR2 expression was regulated, levels of VEGFA and VEGFR2 were decreased, and FX increased eNOS. FX ameliorated symptoms of DN, resulting in marked improvement in hyperglycemia and hyperlipidemia and optimized structure and function of kidneys in db/db mice. FX efficacy was associated with the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways. We verified this potential mechanism and hope that this study will provide benefits for the clinical treatment of DN.
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•Fuxin Granules attenuate symptoms of hyperglycemia and hyperlipidemia in db/db mice.•Fuxin Granules aid kidney lipid droplet deposition and renal function in db/db mice.•Fuxin Granules play a multi-channel regulatory and therapeutic role.•Fuxin Granules inhibit ECM storage in db/db mice by TGF-β1/Smad pathway activation.•Fuxin Granules protect renal function in db/db mice through the VEGF/VEGFR2 pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A new alkaline pectate lyase was firstly successfully cloned according to sequence-derived screening of metagenomic DNA.•The highest yield of pectate lyase activity in recombinant E. coli was ...reported in this study.•Recombinant enzyme exhibited some promising properties for use in bioscouring process.•Recombinant enzyme exhibited high catalytic activity on pectate and natural methylated pectin.
Alkaline pectate lyases (PLs) play an important role in mild and eco-friendly bioscouring pretreatment processes in the textile industry. However, to date, only a few PLs can be applied in industrial-scale production, and many of them exhibit high production cost, low activity, and/or do not meet the treatment requirements. In this study, an alkaline PL gene was cloned from the metagenomic DNA of alkaline environment soils. The gene pelB consisted of 1263 nucleotides and encoded a mature protein (PelB) of 399 amino acids, which was expressed in Escherichia coli. The maximum catalytic activity of the enzyme exhibited a bimodal distribution at pH 8.1 and 9.8 and an optimal temperature of 55°C. The Km and Vmax values of PelB were 1.78g/L and 1084.8μmol/(Lmin) at 45°C, respectively. Substrate specificity analysis demonstrated the high cleavage capability of PelB on a broad range of substrates of natural methylated pectin. Based on the degradation products, PelB was considered to be an endo-acting lyase. Using high-cell-density cultivation in 7-L bioreactor, the highest PL activity (1816.2U/mL) was achieved. Thus, the recombinant PelB, with promising properties for use in bioscouring in the textile pretreatment process, should be a potential enzyme for industrial applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Patients with estrogen receptor α (ERα)-positive breast cancer can be treated with endocrine therapy using anti-estrogens such as tamoxifen; nonetheless, patients often develop resistance limiting ...the success of breast cancer treatment. The potential mechanisms remain elusive. In detail, many miRNAs have been associated with breast cancer tamoxifen resistance, but no studies have addressed the role of miRNA-mediated competitive endogenous RNAs network (ceRNET) in tamoxifen resistance. The ceRNET between CYP4Z1 and pseudogene CYP4Z2P has been revealed to promote breast cancer angiogenesis. However, its function in tamoxifen resistance remains unclear. Here we report CYP4Z1 and CYP4Z2P were downregulated in MCF-7 cells compared with tamoxifen-resistant MCF-7-TamR cells. Enforced upregulation of CYP4Z1- or CYP4Z2P-3′UTR level renders MCF-7 Cells resistant to tamoxifen. We find that overexpression of CYP4Z1- or CYP4Z2P-3′UTR enhances the transcriptional activity of ERα through the activation of ERα phosphorylation. Furthermore, we find that CYP4Z1- and CYP4Z2P-3′UTRs increase ERα activity dependent on cyclin-dependent kinase 3 (CDK3). Reporter gene and western blot assays revealed that CYP4Z1- and CYP4Z2P-3′UTRs act as CDK3 ceRNAs. More importantly, the blocking of CYP4Z1- and CYP4Z2P-3′UTRs reversed tamoxifen resistance in MCF-7-TamR cells. Our data demonstrates that the ceRNET between CYP4Z1 and pseudogene CYP4Z2P acts as a sub-ceRNET to promote CDK3 expression in ER-positive breast cancer and is a potential therapeutic target for treatment of tamoxifen-resistant breast cancer.
•A new critical role of ceRNAs in ER + breast cancer is proposed.•We examine the relationship of CYP4Z2P, CYP4Z1 and CDK3 in breast cancer.•The roles of CYP4Z2P and CYP4Z1 in TAM resistance were further studied.•The novel mechanism provides new insights for TAM resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Proton and heavy ion therapy offer superior relative biological effectiveness (RBE) in the treatment of deep-seated tumors compared with conventional photon radiotherapy due to its Bragg-peak feature ...of energy deposition in organs. Many proton and carbon ion therapy centers are active all over the world. At present, five particle radiotherapy institutes have been built and are receiving patient in China, mainly including Wanjie Proton Therapy Center (WPTC), Shanghai Proton Heavy Ion Center (SPHIC), Heavy Ion Cancer Treatment Center (HIMM), Chang Gung Memorial Hospital (CGMH), and Ruijin Hospital affiliated with Jiao Tong University. Many cancer patients have benefited from ion therapy, showing unique advantages over surgery and chemotherapy. By the end of 2020, nearly 8,000 patients had been treated with proton, carbon ion or carbon ion combined with proton therapy. So far, there is no systemic review for proton and carbon ion therapy facility and clinical outcome in China. We reviewed the development of proton and heavy ion therapy, as well as providing the representative clinical data and future directions for particle therapy in China. It has important guiding significance for the design and construction of new particle therapy center and patients' choice of treatment equipment.
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