1D hollow tubular/2D nanosheet hybrid dimensional porous carbon prepared by one-step carbonization using natural minerals as templates for supercapacitors.

The reasonable construction of one-dimensional (1D)/two-dimensional (2D) hybrid dimensional porous carbon materials with complementary advantages and disadvantages is an important approach to addressing the structural and performance deficiencies of single carbon materials, while also significantly improving the electrochemical performance of super-capacitors. In this study, 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon was synthesized through one-step carbonization using 1D fibrous brucite and 2D layered magnesium carbonate hydroxide as templates. By adjusting the feed ratio of 1D fibrous and 2D layered templates, the morphology, pore structure and specific surface area (SSA) of the prepared 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon were controlled. The prepared hybrid dimensional porous carbons were characterized using scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption. And their electrochemical performance was also studied by cyclic voltammograms (CV), galvanostatic charge/discharge (GCD) and electrochemical impedance spectroscopy (EIS). The results show that the use of templates with different dimensions significantly influences the morphology, pore structure, SSA and electrochemical performance of the synthesized hybrid dimensional porous carbon. The hybrid dimensional porous carbon (3F) exhibits a high specific capacitance and excellent cycling stability. 3F demonstrates the specific capacitance of 245.3 F g-1 at 1 A g-1. Furthermore, the capacity retention rate remains as high as 93.4% after 8000 cycles at 10 A g-1. This work reveals that hybrid dimensional porous carbon composed of 1D hollow carbon tubes and 2D carbon nanosheets has great potential for use in supercapacitor electrode materials.

Coupling Iron Sludge Addition and Intermittent Aeration for Achieving Simultaneous Methanogenesis, Feammox, and Denitrification in a Single Reactor Treating Fish Sludge.

An integrated anaerobic digestion system for the simultaneous removal of carbon and nitrogen from fish sludge was developed by coupling iron sludge supplementation with intermittent aeration. In terms of nitrogen removal, Fe(III) in iron sludge could trigger Feammox reactions and intermittent aeration could drive the Fe(II)/Fe(III) cycle to sustain continuous ammonia removal. Mass balance analysis suggested that nitrate was the main product of Feammox, which was subsequently removed through heterotrophic denitrification. In terms of carbon removal, the Fe(III)-induced dissimilatory iron reduction (DIR) process significantly promoted fish sludge hydrolysis and provided more simple organics for methanogens and denitrifiers, but aeration showed a negative impact on methanogenesis. To promote nitrogen removal and avoid serious methanogenesis inhibition, different aeration intensities were studied. Results showed that compared with the control without aeration or iron sludge addition, aeration for 5 min every 3 days (150 mL/min) contributed to a 29.0% lower NH4+-N concentration and a 12.1% lower total chemical oxygen demand level on day 28, and the decline in methane yield was acceptable (only 13.5% lower). Simultaneous methanogenesis, Feammox, and denitrification in a single reactor treating fish sludge were achieved, which provides a simple and low-cost strategy for the treatment of organic wastewater.

Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention.

Objective: This paper briefly reviews the structure and function of NLRP3 inflammasomes, signaling pathway, relationship with synovitis in KOA, and intervention of traditional Chinese medicine (TCM) in NLRP3 inflammasomes as a means to improve its therapeutic potential and clinical application. Method: Literatures about NLRP3 inflammasomes and synovitis in KOA were reviewed to analyze and discuss. Result: NLRP3 inflammasome can activate NF-κB mediated signal transduction, which in turn causes the expression of proinflammatory cytokines, initiates the innate immune response, and triggers synovitis in KOA. The TCM monomer/active ingredient, decoction, external ointment, and acupuncture regulating NLRP3 inflammasomes are helpful to alleviate synovitis in KOA. Conclusion: The NLRP3 inflammasome plays a significant role in the pathogenesis of synovitis in KOA, TCM intervention targeting the NLRP3 inflammasome can be a novel approach and therapeutic direction for the treatment of synovitis in KOA.

Chlorogenic acid improves intestinal morphology by enhancing intestinal stem-cell activity.

BACKGROUND: Chlorogenic acid (CGA), as one of the most abundant naturally occurring phenolic acids, has been documented to be beneficial for intestinal health. However, the underlying mechanism is still not fully understood. The adult intestinal stem cell is the critical driver of epithelial homeostasis and regeneration. RESULTS: This study hypothesized that CGA exerted intestinal health effects by modulating intestinal stem-cell functions. Lgr5-EGFP mice were treated for 14 days, and intestinal organoids derived from these mice were treated for 3 days, using CGA solution. In comparison with the control group, CGA treatment increased intestinal villous height and crypt depth in mice and augmented the area expansion and the number of budding intestinal organoids. Quantitative polymerase chain reaction (qPCR) analysis revealed that CGA treatment significantly increased the expression of genes coding intestinal stem-cell markers in intestinal tissue and organoids, and upregulated the expression of genes coding secretory cell lineages and enterocytes, although not statistically significantly. Fluorescence-activated cell-sorting analysis further confirmed that CGA augmented the number of stem cells. 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and Ki67 immunostaining results also demonstrated that CGA treatment enhanced intestinal stem-cell proliferation. CONCLUSION: Altogether, our findings indicate that CGA could activate intestinal stem-cell and epithelial regeneration, which could contribute to the improvement of intestinal morphology or organoid growth of mice. This highlights a promising mechanism for CGA as an excellent candidate for the formulation of dietary supplements and functional foods for intestinal protection. © 2023 Society of Chemical Industry.

Employing ATP as a New Adjuvant Promotes the Induction of Robust Antitumor Cellular Immunity by a PLGA Nanoparticle Vaccine.

Tumor vaccines based on synthetic human papillomavirus (HPV) oncoprotein E7 and/or E6 peptides have shown encouraging results in preclinical model studies and human clinical trials. However, the clinical efficacy may be limited by the disadvantages of vulnerability to enzymatic degradation and low immunogenicity of peptides. To further improve the potency of vaccine, we developed a poly(lactide-co-glycolide)-acid (PLGA) nanoparticle, which encapsulated the antigenic peptide HPV16 E744-62, and used adenosine triphosphate (ATP), one of the most important intracellular metabolites and an endogenous extracellular danger signal for the immune system, as a new adjuvant component. The results showed that PLGA nanoparticles increased the in vivo stability, lymph node accumulation, and dendritic cell (DC) uptake of the E7 peptide; in addition, ATP further increased the migration, nanoparticle uptake, and maturation of DCs. Preventive immunization with ATP-adjuvanted nanoparticles completely abolished the growth of TC-1 tumors in mice and produced long-lasting immunity against tumor rechallenge. When tumors were fully established, therapeutic immunization with ATP-adjuvanted nanoparticles still significantly inhibited tumor progression. Mechanistically, ATP-adjuvanted nanoparticles significantly improved the systemic generation of antitumor effector cells, boosted the local functional status of these cells in tumors, and suppressed the generation and tumor infiltration of immunosuppressive Treg cells and myeloid-derived suppressor cells. These findings indicate that ATP is an effective vaccine adjuvant and that nanoparticles adjuvanted with ATP were able to elicit robust antitumor cellular immunity, which may provide a promising therapeutic vaccine candidate for the treatment of clinical malignancies, such as cervical cancer.

Weak magnetic field significantly enhances methane production from a digester supplemented with zero valent iron.

Weak magnetic field (WMF) provided by a magnet was proposed to enhance CH4 production from a swine manure-fed digester supplemented with micron-sized zero valent iron (ZVI). Compared to the control without ZVI addition and WMF application (RControl), treatments that included ZVI only (RZVI) and coupled WMF with ZVI (RZVI/WMF) increased the CH4 production by 77.0% and 124.5%, respectively. As evidenced by the elevated levels of total soluble iron, WMF apparently promoted the corrosion of ZVI, providing extra H2 for hydrogenotrophic methanogenesis and creating a more reductive environment to reduce propionic-type fermentation. Microbial analysis results revealed that the relative abundance of Methanothrix (capable of accepting electrons) in RZVI/WMF were 75.1% higher than that in RZVI. Essentially, WMF application promoted the direct interspecies electron transfer-based methanogenesis by (1) providing more electrons as the direct substrate, and (2) inducing Lorentz force to facilitate the mass transfer between the released electrons and the methanogens.

Effects of light intensity on oxygen distribution, lipid production and biological community of algal-bacterial granules in photo-sequencing batch reactors.

The effects of light intensity (0-225 µmol m-2 s-1) on oxygen distribution, lipid production and biological community structure of algal-bacterial granules were investigated in six identical photo-sequencing batch reactors (with a dark/light cycle of 12 h/12 h). Typically green algal-bacterial granules could be developed at a light intensity of ≥135 µmol m-2 s-1. The lipid content was significantly increased under higher light intensity, while the percentage of saturated fatty acid methyl esters was remarkably decreased. Results showed that light intensity ≥90 µmol m-2 s-1 yielded enough O2 production from algae, creating aerobic/anoxic zone (0.3-0.6 mg-O2/L) in the core of granules and thus efficient algal-bacterial symbiosis system. Enhanced nitrogen and phosphorus removals were achieved in the reactors with stronger light illumination, probably attributable to the enrichment of ammonia oxidizing bacteria (Comamonadaceae and Nitrosomonadaceae) and algae (Navicula and Stigeoclonium). Illuminance ≥180 µmol m-2 s-1 was found to be unfavorable for Nitrospiraceae.

Enhanced anaerobic digestion of ammonia-rich swine manure by zero-valent iron: With special focus on the enhancement effect on hydrogenotrophic methanogenesis activity.

Zero-valent iron (ZVI) supplementation for improving anaerobic digestion (AD) of ammonia-rich swine manure (initial ammonia-N ∼5000 mg/L) was tested. The addition of 5 g/L ZVI powder apparently accelerated the acidification process to produce more volatile fatty acids (VFAs) and optimized the fermentation type by contributing to a lower system oxidation-reduction potential (ORP) level of -181.7 to -250.0 mV favorable for ethanol-type and butyric-type fermentation during day 14-30, in comparison with that of -164.3 to -216.3 mV in the control group favorable for propionic-type. Overall, ZVI significantly decreased the proportion of propionic acid from 49.8% to 30.9% while increased the proportion of n-butyric acid from 6.8% to 18.7%. Microbial analysis revealed that fast growing and ammonia-tolerant hydrogenotrophic Methanoculleus species were enriched with ZVI, helping achieve a 54.2% higher CH4 yield relative to control. Results from this study demonstrated the potential of ZVI addition to enhance AD of ammonia-rich animal manure.

Fertilizer potential of liquid product from hydrothermal treatment of swine manure.

Compared with composting, hydrothermal treatment (HTT) technology can dramatically shorten the duration for manure waste treatment. This study firstly investigated the effect of HTT on solubilization of N, P and organics from swine manure, and then evaluated the phytotoxicity of liquid product from hydrothermally treated manure by seed germination test. Results show that 98% of N in manure could be converted into soluble form after HTT at 200 °C for 60 min. Soluble P in hydrothermally treated manure (at 150 °C for 60 min) was 2.7 times that in raw manure. The germination indices (GI) were all greater than 100% when the liquid product (from HTT at 150 °C for 60 min) or its diluted samples being used. Results from this study suggest that HTT could be a promising technology for producing safe and value-added liquid fertilizers from swine manure.

Biochar addition for accelerating bioleaching of heavy metals from swine manure and reserving the nutrients.

Biochar was applied during the bioleaching of heavy metals (HMs) from swine manure (SM), in an attempt to accelerate the HMs removal rates and to reduce the losses of nutrient elements (nitrogen and phosphorus). Results showed that the addition of biochar (5gL-1) could not only significantly shorten the leaching time of HMs (Cu, Zn, Mn and Cd) from 10 (control) to 7days with a high solubilization efficiency of 90%, but also decrease the total nitrogen loss efficiency by 42.7% from 180.3 (control) to 103.3mgL-1 in the leachate. In addition, biochar addition facilitated Fe2+ oxidation rate, achieving much better pH and ORP conditions. Electronic conductivity and adsorption properties of biochar with changed microbial community probably contributed a lot to the enhanced HMs solubilization and reduced nitrogen loss during bioleaching. Although the addition of biochar only slightly reduced the total amount of phosphorus loss, the bioavailable phosphorus in SM after bioleaching was markedly increased by 13.7%.

Increased plasma orexin-A levels in patients with insomnia disorder are not associated with prepro-orexin or orexin receptor gene polymorphisms.

Orexins, also known as hypocretins, play a regulatory role in the sleep-wake cycle by activating orexin receptors. Previous animal studies have shown that sleep deprivation can elevate orexinergic peptide levels. However, the relationship between insomnia disorder and orexin-A levels in humans has not been explored. In the current study, we examined plasma orexin-A levels in patients with insomnia disorder and in normal sleepers. We also studied the possible mechanisms underlying changes in orexin-A levels between the study groups; this included investigations of prepro-orexin and orexin receptor gene polymorphisms as well as exploration of other variables. We measured plasma orexin-A levels in 228 patients with insomnia disorder and 282 normal sleepers. The results indicated that the patients with insomnia disorder had significantly higher orexin-A levels than normal sleepers (63.42±37.56 vs. 54.84±23.95pg/ml). A positive relationship was detected between orexin-A level and age in patients with insomnia disorder. Orexin-A levels were elevated in relation to course of insomnia, as well as in relation to increased Insomnia Severity Index score. None of the evaluated prepro-orexin gene single nucleotide polymorphisms were informative between the two study populations. After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups. It is suggested that the increased plasma orexin-A levels in patients with insomnia disorder are associated with the course and severity of insomnia, but not with prepro-orexin and orexin receptor gene polymorphisms.

RETRACTED: Low density lipoprotein receptor targeted doxorubicin/DNA-Gold Nanorods as a chemo- and thermo-dual therapy for prostate cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors and sanctioned by the Editor-in-Chief. The authors found errors in the data presentation - apoptotic statistics and in vivo distribution - which makes the conclusion not representative. The authors express sincere apologies for the error and inconvenience to readers.

Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii.

A. baumannii infections are becoming more and more serious health issues with rapid emerging of multidrug and extremely drug resistant strains, and therefore, there is an urgent need for the development of nonantibiotic-based intervention strategies. This study aimed at identifying whether an outer membrane protein with molecular weight of about 22 kDa (Omp22) holds the potentials to be an efficient vaccine candidate and combat A. baumannii infection. Omp22 which has a molecule length of 217 amino acids kept more than 95% conservation in totally 851 reported A. baumannii strains. Recombinant Omp22 efficiently elicited high titers of specific IgG in mice. Both active and passive immunizations of Omp22 increased the survival rates of mice, suppressed the bacterial burdens in the organs and peripheral blood, and reduced the levels of serum inflammatory cytokines and chemokines. Opsonophagocytosis assays showed in vitro that Omp22 antiserum had highly efficient bactericidal activities on clonally distinct clinical A. baumannii isolates, which were partly complements-dependent and opsonophagocytic killing effects. Additionally, administration with as high as 500 µg of Omp22 didn't cause obvious pathological changes in mice. In conclusion, Omp22 is a novel conserved and probably safe antigen for developing effective vaccines or antisera to control A. baumannii infections.

Volatile fatty acids (VFAs) production from swine manure through short-term dry anaerobic digestion and its separation from nitrogen and phosphorus resources in the digestate.

The sustainability of an agricultural system depends highly upon the recycling of all useful substances from agricultural wastes. This study explored the feasibility of comprehensive utilization of C, N and P resources in swine manure (SM) through short-term dry anaerobic digestion (AD) followed by dry ammonia stripping, aiming at achieving (1) effective total volatile fatty acids (VFAs) production and separation; (2) ammonia recovery from the digestate; and (3) preservation of high P bioavailability in the solid residue for further applications. Specifically, two ammonia stripping strategies were applied and compared in this work: (I) ammonia stripping was directly performed with the digestate from dry AD of SM (i.e. dry ammonia stripping); and (II) wet ammonia stripping was conducted by using the resultant filtrate from solid-liquid separation of the mixture of digestate and added water. Results showed that dry AD of the tested SM at 55 °C, 20% TS and unadjusted initial pH (8.6) for 8 days produced relatively high concentrations of total VFAs (94.4 mg-COD/g-VS) and ammonia-N (20.0 mg/g-VS) with high potentially bioavailable P (10.6 mg/g-TS) remained in the digestate, which was considered optimal in this study. In addition, high ammonia removal efficiencies of 96.2% and 99.7% were achieved through 3 h' dry and wet stripping (at 55 °C and initial pH 11.0), respectively, while the total VFAs concentration in the digestate/filtrate remained favorably unchanged. All experimental data from the two stripping processes well fitted to the pseudo first-order kinetic model (R(2) = 0.9916-0.9997) with comparable theoretical maximum ammonia removal efficiencies (Aeq, >90%) being obtained under the tested dry and wet stripping conditions, implying that the former was more advantageous due to its much higher volumetric total ammonia-N removal rate thus much smaller reactor volume, less energy/chemicals consumption and no foaming problems. After 8 days' dry AD and 3 h' dry ammonia stripping, the separated liquid containing VFAs and the recovered ammonia were both marketable products, and the solid residues with averagely higher C/N ratios of 25.7 than those of raw SM (18.0) meanwhile maintaining a relatively high bioavailable P content of 8.1 mg/g-TS can serve as better feedstock for methane fermentation.

Species and distribution of inorganic and organic phosphorus in enhanced phosphorus removal aerobic granular sludge.

The species and distribution of phosphorus (P) in an enhanced biological phosphorus removal (EBPR)-aerobic granular sludge (AGS) were fractionated and further analyzed. Results showed that microbial cells, extracellular polymeric substances (EPS) and mineral precipitates contributed about 73.7%, 17.6% and 5.3-6.4% to the total P (TP) of EBPR-AGS, respectively. Inorganic P (IP) species were orthophosphate, pyrophosphate and polyphosphate among which polyphosphate was the major P species in the AGS, cells and EPS. Monoester and diester phosphates were identified as the organic P (OP) species in the AGS and cells. Hydroxyapatite (Ca5(PO4)3OH) and calcium phosphate (Ca2(PO4)3) were the dominant P minerals accumulated in the core of the granules. Cells along with polyphosphate were mainly in the outer layer of AGS while EPS were distributed in the whole granules. Based on the above results, the distribution of IP and OP species in AGS has been conceived.

Characterization and bioactivity of polysaccharides obtained from pine cones of Pinus koraiensis by graded ethanol precipitation.

Pinus koraiensis polysaccharides (PKP) were extracted by hot water from P. koraiensis pine cones. Five polysaccharide fractions named PKP-A, PKP-B, PKP-C, PKP-D and PKP-E were successfully separated at final ethanol concentrations of 30%, 50%, 60%, 70% and 80%, respectively. HPLC, FT-IR, GC-MS and automatic amino-acid analysis were applied to investigate their chemical characteristics. Monosaccharide component analysis indicated that the five fractions were all composed of D-ribose, L-rhamnose, L-arabinose, D-xylose, D-mannose, D-glucose and D-galactose, but their molar ratios were quite different. HPLC results revealed that the polysaccharides precipitated by higher concentrations of ethanol solution had lower molecular masses. Moreover, the antioxidant activities of the five fractions were studied on the basis of hydroxyl radical and ABTS radical scavenging tests. The five graded polysaccharide fractions exhibited good inhibitory power, and MTT tests in vitro showed the IC50 of PKP-A and PKP-E were 1,072.5 and 2,070.0 µg · mL-1, respectively. These results demonstrated that the PKP could be a potential source of natural antioxidants or dietary supplements.

Chemical composition and antioxidant activities of three polysaccharide fractions from pine cones.

The traditional method of gas chromatography-mass spectrometry for monosaccharide component analysis with pretreatment of acetylation is described with slight modifications and verified in detail in this paper. It was then successfully applied to the quantitative analysis of component monosaccharides in polysaccharides extracted from the pine cones. The results demonstrated that the three pine cone polysaccharides all consisted of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose in different molar ratios. According to the recovery experiment, the described method was proved accurate and practical for the analysis of pine cone polysaccharides, meeting the need in the field of chemical analysis of Pinus plants. Furthermore; the chemical characteristics, such as neutral sugar, uronic acids, amino acids, molecular weights, and antioxidant activities of the polysaccharides were investigated by chemical and instrumental methods. The results showed that the chemical compositions of the polysaccharides differed from each other, especially in the content of neutral sugar and uronic acid. In the antioxidant assays, the polysaccharide fractions exhibited effective scavenging activities on ABTS radical and hydroxyl radical, with their antioxidant capabilities decreasing in the order of PKP > PAP > PSP. Therefore, although the polysaccharide fractions had little effect on superoxide radical scavenging, they still have potential to be developed as natural antioxidant agents in functional foods or medicine.

Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression.

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa.

Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27.

Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.

Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1.

Yin Yang 1 (YY1) is a multifunctional protein with regulatory potential in tumorigenesis. Ample studies demonstrated the activities of YY1 in regulating gene expression and mediating differential protein modifications. However, the mechanisms underlying YY1 gene expression are relatively understudied. G-quadruplexes (G4s) are four-stranded structures or motifs formed by guanine-rich DNA or RNA domains. The presence of G4 structures in a gene promoter or the 5'-UTR of its mRNA can markedly affect its expression. In this report, we provide strong evidence showing the presence of G4 structures in the promoter and the 5'-UTR of YY1. In reporter assays, mutations in these G4 structure forming sequences increased the expression of Gaussia luciferase (Gluc) downstream of either YY1 promoter or 5'-UTR. We also discovered that G4 Resolvase 1 (G4R1) enhanced the Gluc expression mediated by the YY1 promoter, but not the YY1 5'-UTR. Consistently, G4R1 binds the G4 motif of the YY1 promoter in vitro and ectopically expressed G4R1 increased endogenous YY1 levels. In addition, the analysis of a gene array data consisting of the breast cancer samples of 258 patients also indicates a significant, positive correlation between G4R1 and YY1 expression.