Search

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane‐associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β‐catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β‐catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression., By reducing the level of MAGI3 protein, HPV18 E6 promotes cervical cancer cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 is preferentially associated with downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in cervical cancer. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in cervical cancer progression.

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.

Problem definition: Many small businesses (suppliers) use web platforms (retailers) to sell their products on a consignment basis. Suppliers are often financially constrained, which affects their profits. Academic/practical relevance: We derive the equilibrium terms of the loan that a retailer will offer to a supplier in a consignment selling environment and their implications for supply chain efficiency. Our model is inspired by the lending program initiated by a major web platform owner. Methodology: We formulate and solve a Stackelberg game. The retailer sets loan terms that may include a debt seniority requirement. The supplier may either accept the retailer’s offer or borrow only from the bank or rely solely on its own capital. A competitively priced bank loan is the supplier’s default option. Results: There exist parameter values for which the on-equilibrium loan terms include retailer debt seniority as well as parameter values that do not. In the latter case, the supplier makes the bank the senior lender. The retailer’s debt seniority choice depends on the supplier’s working capital. When the retailer chooses to be the senior lender, its loan terms may induce the supplier to produce more than the first-best quantity. Managerial implications: Direct financing under equilibrium loan terms weakly improves the expected profits of both the retailer and the supplier. However, it may induce the supplier to produce less than or equal to or greater than the first-best production quantity. Loan limits serve to reduce overproduction.

Nucleosomal histones are barriers to the DNA repair process particularly at DNA double-strand breaks (DSBs). However, the molecular mechanism by which these histone barriers are removed from the sites of DNA damage remains elusive. Here, we have generated a single specific inducible DSB in the cells and systematically examined the histone removal process at the DNA lesion. We found that histone removal occurred immediately following DNA damage and could extend up to a range of few kilobases from the lesion. To examine the molecular mechanism underlying DNA damage-induced histone removal, we screened histone modifications and found that histone ADP-ribosylation was associated with histone removal at DNA lesions. PARP inhibitor treatment suppressed the immediate histone eviction at DNA lesions. Moreover, we examined histone chaperones and found that the FACT complex recognized ADP-ribosylated histones and mediated the removal of histones in response to DNA damage. Taken together, our results reveal a pathway that regulates early histone barrier removal at DNA lesions. It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.

Large micron-sized Y3Al5O12:Ce3+ phosphors were successfully synthesized by a cost-effective method using eutectic mixtures of YF3–AlF3 as the molten-salt flux for high-power laser diodes applications. The crystallinity, morphology, particle size, thermal quenching properties of the phosphors were measured, respectively. The phosphor particle size increased with increasing amount of flux, and the medium size (D50) could reach 40 μm when adding 25 wt% YF3–AlF3. The phosphors with larger particle size did not only exhibit superior optical performances but also excellent thermal-quenching characteristics, leading to a lower surface temperature and a higher radiant efficiency when excited by a high-power laser.

The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control due to the fact that their teeth share highly conserved and well-characterized developmental processes and their developmental tempo vary notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrate that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1- to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo and the dental mesenchymal FGF8 could be a pivotal factor in controlling developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.

Semiconducting minerals are ubiquitous in soil and their association with microbes often affects the environment. In this study, the impacts of zinc sulfide (ZnS, used as a model compound for semiconducting sphalerite) on As/Fe mobility of flooded tailing soils under dark and intermittent illumination conditions were elucidated for the first time. Microbial reductive dissolution of As(V) and Fe(III) was more pronounced under intermittent illumination than under dark conditions. In ZnS-amended soils, release of As(III) and Fe(II) was 1.3 and 1.7 times higher, respectively, under intermittent illumination than the highest concentrations released from soils amended with acetate alone under dark conditions (12741.1 ± 714.3 μg/L and 37.9 ± 2.3 mg/L, respectively). However, under dark conditions in ZnS-amended soil, the release of As(III) and Fe(II) was 0.8 and 0.7 times that of the highest concentrations released from soils amended with acetate under dark conditions, respectively. Treatment with ZnS potentially decreased the abundance of several metal-reducing bacteria (e.g., Bacillus, Geobacter, Clostridium, and Desulfitobacterium), which resulted in lower As/Fe reduction than for the acetate alone treatment under dark conditions. However, under intermittent illumination, the excited mineral photoholes were scavenged by humic/fulvic acids, and photoelectrons were synchronously separated and participated in the microbial electron chain. The fortification provided by the photoelectrons subsequently boosted As/Fe reduction, even though there was a lower abundance of metal-reducing bacteria. Hence, this study provides an in-depth understanding of the impacts of semiconducting minerals on the fates of metal pollutants, microbial diversity, and the bioavailability of dissolved organic matter in flooded soils.

By the ordered tree inclusion we will check whether a pattern tree P can be included in a target tree T, where the order of siblings in both P and T matters. This problem has many applications in practice, such as retrieval of documents, data mining, and RNA structure matching. In this paper, we propose an efficient algorithm for this problem. Its time complexity is bounded by ${\text{O}(\vert }T\vert \cdot \;min\{h_{P}{,\;\vert \text{leaves(}}P)\vert \})$O(|T|·min{hP,|leaves(P)|}), with ${\text{O}(\vert }T\vert + \vert P\vert)$O(|T|+|P|) space being used, where hP (hT) represents the height of P (resp., T) and leaves (P) stands for the set of the leaves of P. Up to now the best algorithm for this problem needs $\Theta (\vert T\vert \cdot \vert leaves(P)\vert)$Θ(|T|·|leaves(P)|) time and ${\text{O}(\vert }P\vert + \vert T\vert)$O(|P|+|T|) space. Extensive experiments have been done, which show that the new algorithm can perform much better than the existing ones in practice.

Engineering of functional vascularized liver tissues holds great promise in addressing donor organ shortage for transplantation. Whole organ decellularization is a cell removal method that retains the native vascular structures of the organ such that it can be anastomosed with the recipient circulation after recellularization with healthy cells. However, a main hurdle to successful implantation of bioengineered organ is the inability to efficiently re-endothelialize the vasculature with a functional endothelium, resulting in blood clotting which is the primary cause of failure in early transplant studies. Here, we present an efficient approach for enhancing re-endothelialization of decellularized rat liver scaffolds by conjugating the REDV cell-binding domain to improve attachment of endothelial cells (EC) on vascular wall surfaces. In order to facilitate expression and purification of the peptide, REDV was fused with elastin-like peptide (ELP) that confers thermally triggered aggregation behavior to the fusion protein. After validating the adhesive properties of the REDV-ELP peptide, we covalently coupled REDV-ELP to the blood vasculature of decellularized rat livers and seeded EC using perfusion of the portal vein. We showed that REDV-ELP increased cell attachment, spreading and proliferation of EC within the construct resulting in uniform endothelial lining of the scaffold vasculature. We further observed that REDV-ELP conjugation dramatically reduced platelet adhesion and activation. Altogether, our results demonstrate that this method allowed functional re-endothelialization of liver scaffold and show great potential toward the generation of functional bioengineered liver for long-term transplantation. Statement of Significance There is a critical need for novel organ replacement therapies as the grafts for transplantation fall short of demand. Recent advances in tissue engineering, through the use of decellularized scaffolds, have opened the possibility that engineered grafts could be used as substitutes for donor livers. However, successful implantation has been challenged by the inability to create a functional vasculature. Our research study reports a new strategy to increase efficiency of endothelialization by increasing the affinity of the vascular matrix for endothelial cells. We functionalized decellularized liver scaffold using elastin-like peptides grafted with REDV cell binding domain. We showed that REDV-ELP conjugation improve endothelial cell attachment and proliferation within the scaffold, demonstrating the feasibility of re-endothelializing a whole liver vasculature using our technique.

Mesothelin (MSLN) is a tumor-associated antigen over-expressed on the cell surface of various malignant tumor cells, including majority of mesothelioma and ovarian cancer. MSLN-directed therapy has been intensively studied in preclinical and clinical settings. However, the clinical efficacy and safety of mesothelin-targeted therapy remains to be demonstrated. To identify a safe and effective target for CAR-T cell therapy in solid tumors, we used artificial intelligent platform developed with public and private RNA transcription database to identify cancer-associated antigens caused by alternative spicing. One of interesting targets is an alternative spicing isoform from MSLN. Human MSLN transcript has at least three isoforms. The isoform 1 is the predominant transcript detected in normal and tumor tissues and has been a promising target for cancer immunotherapy. The isoform 2 is the minor transcript using alternatively spliced exons producing 8 additional amino acids insertion compared to isoform 1. The isoform 3 produces a truncated and soluble MSLN. Our data demonstrated that MSLN isoform 2 is specifically expressed in ovarian cancers but not normal tissues, confirmed by Q-PCR studies. Furthermore, we generated mouse hybridoma antibodies specifically targeting MSLN isoform 2. The antibody specificity was screened and confirmed by ELISA-based reaction to MSLN isoform 2-specific peptide and flow cytometry-based binding to 293T cells overexpressing MSLN isoform 2 but not isoform 1 proteins. We further detected the endogenous MSLN isoform 2 expression in human mesothelioma cell line NCI H226 and further confirmed MSLN isoform 2 expression on human primary mesothelioma and ovarian cancer tissue but not normal tissues by immunohistochemistry staining. To study if targeting MSLN isoform 2 with chimeric antigen receptor (CAR) can control the tumor growth, we made CAR retrovirus construct and showed that genetically modified allogenic gamma-delta T cells expressing CAR for MSLN isoform 2 can kill human mesothelioma cells in vitro and in vivo. In summary, we have demonstrated that MSLN isoform 2 is a tumor-specific antigen, which can be targeted for CAR-T cell therapy. Citation Format: Xiaohong Wang, Yibin Chen, Anupama Gopisetty, Leonardo Mirandola, Lucia Piccotti, Quynh Nguyen, Maurizio Chiriva-Internati. Mesothelin isoform 2 is a novel target for allogenic CARγδT cell therapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1534.

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch‐like enoyl-coenzyme A hydratase (ECH)‐associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Engineered liver grafts for transplantation with sufficient hepatic function have been developed both in small and large animal models using the whole liver engineering approach. However, repopulation of the bile ducts in the whole liver scaffolds has not been addressed yet. In this study, we show the feasibility of repopulating the bile ducts in decellularized rat livers. Biliary epithelial cells were introduced into the bile ducts of the decellularized liver scaffolds with or without hepatocytes in the parenchymal space. The recellularized grafts were cultured under perfusion for up to 2 days and histological analysis revealed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement highly comparable to the native tissue. The grafts were viable and functional as confirmed by both albumin and urea assay results and the gene expression analysis of biliary epithelial cells in recellularized liver grafts. This study provides the proof-of-concept results for rat liver grafts co-populated with parenchymal and biliary epithelial cells.

Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear. Here, we describe a new method to utilize discarded livers to make transplantable new liver grafts. We show that marginal donor livers damaged due to warm ischemia could be treated with machine perfusion to yield 39 million viable hepatocytes per gram of liver, similar to fresh livers, and these cells could be used to repopulate decellularized liver matrix (DLM) scaffolds to make transplantable liver grafts. The hepatocytes from recovered livers sustained their characteristic epithelial morphology while they exhibited slightly lower protein synthesis functions both in plate cultures and in recellularized liver grafts. The dampened protein synthesis was attributed to residual endoplasmic reticulum stress found in recovered cells. The results here represent a unique approach to reengineer transplantable liver grafts solely from discarded organs.

In this research, Ca-α-SiAlON phosphors with compositions of Ca 1− x Eu x Si 9 Al 3 ON 15 ( x =2.5%, 5.0%, 7.5%, 10.0% and 15.0%) were synthesized by heterogeneous precipitation processing. The solid state reaction and nitridation reaction were completed at 1400–1500 °C for 12 h in a flow of N 2 –H 2 (H 2 , 5 vol%). The phase of α-SiAlON was prepared at 1450 °C for 12 h. The phosphors showed strong and broad absorption in the range of 230–530 nm and a broad orange–yellow emission band ranging from 500 to 700 nm for peaking at 582–600 nm which were corresponding to the phosphor prepared by the conventional solid state reaction. The results indicate a concentration quenching effect at x ≥7.5% and a systematic red-shift in emission wavelength as the heat-treatment temperature or the Eu 2+ concentration increases. The quantum efficiency of the sample heat-treated at 1600 °C for 12 h, reached 70.56% (internal) and 45.7% (external) with the 450 nm excitation. The corresponding CCT (Correlated color temperature) range of white LED lamps consisting of a blue LED chip and the Ca-α-SiAlON phosphor can be ranging from 2000 to 2700 K.

A new method of uniform sampling is evaluated in this paper. The items and indexes were adopted to evaluate the rationality of the uniform sampling. The evaluation items included convenience of operation, uniformity of sampling site distribution, and accuracy and precision of measured results. The evaluation indexes included operational complexity, occupation rate of sampling site in a row and column, relative accuracy of pill weight, and relative deviation of pill weight. They were obtained from three kinds of drugs with different shape and size by four kinds of sampling methods. Gray correlation analysis was adopted to make the comprehensive evaluation by comparing it with the standard method. The experimental results showed that the convenience of uniform sampling method was 1 (100%), odds ratio of occupation rate in a row and column was infinity, relative accuracy was 99.50–99.89%, reproducibility RSD was 0.45–0.89%, and weighted incidence degree exceeded the standard method. Hence, the uniform sampling method was easy to operate, and the selected samples were distributed uniformly. The experimental results demonstrated that the uniform sampling method has good accuracy and reproducibility, which can be put into use in drugs analysis.

Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359]

Severe liver disease is the 12th leading cause of death in the USA, with organ transplantation often being the only viable option for treatment. However, due to the shortage of viable donor livers, it is estimated that over 1200 patients died in 2015 while waiting for liver transplantation. This highlights the need for alternative sources of viable organs. In this study, we describe a method that provides the groundwork for the development of functional liver grafts. The approach described here is for removal of cells from intact livers and subsequently repopulating them with functional liver cells. Briefly, rat livers are harvested and subjected to a series of perfusion decellularization steps using an anionic detergent such that an intact decellularized liver matrix (DLM) scaffold with preserved vascular architecture is obtained. Further, we describe methods to recellularize DLM scaffolds with adult primary hepatocytes, creating a liver graft that exhibits hepatic functions in vitro.

The lead-free, low-softening point ZnO-Bi2O3-B2O3 glass with low permittivity, low loss and small coefficient of thermal expansion was prepared by melt-quenching method. ZnO-Bi2O3-B2O3 glass + Al2O3 system were prepared below 850°C by the conventional ceramic route. Sintering behavior and microstructure of this system were investigated using X-ray diffraction, differential scanning calorimetry, and scanning electron microscopic techniques. Results revealed that ZnO-Bi2O3-B2O3 glass and Al2O3 reacted during the firing process, which led to the formation of ZnAl2O4. Glass concentration needed to be 65 wt% for better densification. The dense system sintered at 825°C for 30 min exhibited good dielectric properties: small permittivity of 5.73 and low loss tangent of 8.94 × 10−4 at 1 MHz. Its coefficient of thermal expansion (5.57 × 10−6/K) well matched to that of GaAs chip (5.6 × 10−6/K). The bending strength was also characterized (129.9 MPa). The prepared system was suitable for LTCC application.

The focus of this study is on the A+B transportation procurement mechanism, which uses the proposed cost (A component) and the proposed time (B component) to score contractors’ bids. Empirical studies have shown that this mechanism shortens project durations. We use normative models to study the effect of certain discretionary parameters set by state transportation agencies on contractors’ equilibrium bidding strategies, winner selection, and actual completion times. We model the bidding environment in detail including multi-dimensional bids, contractors’ uncertainty about completion times, and reputation cost. The latter refers to a private penalty that accrues to tardy contractors from increased cost of posting bonds and reduced prospects of winning future projects. Our model explains why contractors may skew line-item bids and why winners frequently finish earlier than bid. It has several policy implications as well. For example, we recommend that agencies set the daily incentive, disincentive, and road user cost to be equal and not cap incentives. This is a departure from current practice, where incentives are often capped and weaker than penalties. Furthermore, we show that agencies may be justified in setting daily road user cost strictly smaller than the true cost of traffic disruption during construction.

H2A.B is a unique histone H2A variant that only exists in mammals. Here we found that H2A.B is ubiquitously expressed in major organs. Genome-wide analysis of H2A.B in mouse ES cells shows that H2A.B is associated with methylated DNA in gene body regions. Moreover, H2A.B-enriched gene loci are actively transcribed. One typical example is that H2A.B is enriched in a set of differentially methylated regions at imprinted loci and facilitates transcription elongation. These results suggest that H2A.B positively regulates transcription elongation by overcoming DNA methylation in the transcribed region. It provides a novel mechanism by which transcription is regulated at DNA hypermethylated regions.

The existing literature has revealed the questionable economic benefits of hosting such events, while scholars would still hold an optimistic view of the benefits of place branding and promotion. This paper raises a critical question to this view by examining the effectiveness of hosting pro-tourism events for destination branding. This paper collects massive tourist online reviews and conducts sentiment analysis to examine this issue based on the case of Sanya city in China. The study finds that: (1) there is no solid evidence to show that Sanya’s tourism-related events have a significant positive impact on its destination branding; (2) in the short term, that is fewer than six months, culture-related events were more effective in improving the destination’s image; (3) in the long term, that is, from six months to two years, sports-related events had more positive sentiment impacts, while negative sentiment impacts were largely the result of tourist rip-off incidents. In doing so, this paper argues that hosting tourism events would not be a sustainable way of destination branding, unless the event is meant for other interests. This effort provides an innovative approach for understanding the impacts of tourism events to destination branding in a more critical manner.

A new binary metal hydrate photocatalyst CdSnO 3 ·3H 2 O was synthesized from Cd(CH 3 COO) 2 and SnCl 4 ·5H 2 O via a facile homogenous precipitation method. The photocatalytic activities of samples were evaluated by the photocatalytic degradation of volatile organic compounds (VOCs) in O 2 gas stream under ultraviolet light irradiation. The results demonstrated that the typical CdSnO 3 ·3H 2 O sample had an average particle size of about 16 nm, a band gap of 4.4 eV, and a specific surface area of 91.8 m 2 g −1 . The comparison of CdSnO 3 ·3H 2 O synthesized at different pH values showed that the photocatalytic activities of CdSnO 3 ·3H 2 O synthesized at pH 7 and 8 were higher than that of the samples synthesized at pH 6 and 9. Contrast to commercial P25-TiO 2 , the activity of this new photocatalyst was better. The conversion ratio of benzene was about 45% and 5%, corresponding to the mineralization ratio was about 60% and 25%, respectively. CdSnO 3 ·3H 2 O also exhibited high photocatalytic activities towards cyclohexane and acetone. Then, the mechanism of the reaction on the new photocatalyst was discussed. Hence, the facile synthesis of this photocatalyst and its outstanding photocatalytic performance for VOCs are favorable to its potential application in the environmental remedy field.

TET2 is shown to associate with OGT, which catalyses O-GlcNAcylation, and the two enzymes are found together at transcription start sites; TET2 facilitates the activity of OGT in O-GlcNAcylation of histone 2B, and epigenetic modifications to both DNA and histones by TET2 and OGT may be important in gene transcription regulation. Enzymes of the TET family catalyse the oxidation of 5-methylcytosine, the 'fifth base' in DNA, into derivatives such as 5-hydroxymethylcytosine, and can influence gene expression. Here, Xiaochun Yu and colleagues show that TET2 associates with O-linked β-N-acetylglucosamine transferase (OGT), an enzyme that catalyses O-GlcNAcylation, and that the two proteins are found concurrently at transcriptional start sites. TET2 facilitates the activity of OGT in O-GlcNAcylation of histone H2B, a histone mark associated with active genes. Thus as well as influencing histone modifications, TET2 can affect DNA modifications of potential importance in transcription regulation Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine1 and regulate gene transcription2,3,4,5. However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive5,6. Using protein affinity purification, here we search for functional partners of TET proteins, and find that TET2 and TET3 associate with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation) in vivo7,8. TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription start sites. Downregulation of TET2 reduces the amount of histone 2B Ser 112 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription.

To controllably construct ZnO-base heterostructures, unique ZnO hexagonal quasi-hourglasses have been synthesized by a microwave-assisted hydrothermal approach. The phase purity and the morphologies of as-prepared samples have been determined by using X-ray powder diffractometer, field-emission scanning electron microscopy and transmission electron microscopy. We have rationally discussed the growth and reaction mechanism and revealed the morphological evolution of ZnO hexagonal quasi-hourglasses. Dodecylamine, as well as the initial concentration of zinc source, the reaction temperature and time, play an important part in the synthesis of ZnO hexagonal quasi-hourglasses. Between ZnO and Zn5(OH)8(NO3)2, a reversible reaction seldom reported occurs in a circular manner as the reaction proceeds continuously. The presence of ZnO multipods in the products and the controllable synthesis of half of ZnO hexagonal quasi-hourglass betoken a possibility to synthesize ZnO hierarchical architectures, even ZnO-base heterostructures by using this kind of ZnO building blocks.

Two facile and green methods without any templates, catalysts, surfactants or organic solvents were applied to synthesize ZnSn(OH)6 nanoparticles, i.e. homogeneous precipitation (HP) and hydrothermal (HT). The photocatalytic activities were evaluated on the degradation of organic pollutants under ultraviolet light illumination. Compared to commercial P25, the photoactivity of ZnSn(OH)6 was remarkably improved. The conversion and mineralization ratio of the photocatalytic degradation of benzene by the ZnSn(OH)6-HP were up to 75% and 68%, which is about 20 and 2 times higher than that of P25. The ZnSn(OH)6 has also exhibited high performance toward other persistent organic compounds as well as methyl orange in suspended solution. The order of photodegradation efficiencies of different catalysts was ZnSn(OH)6-HP > P25 > ZnSn(OH)6-HT. Based on the characterization results and the detection of active species, the possible mechanism of the high photocatalytic activity of ZnSn(OH)6-HP was discussed. The simplified synthesis of zinc hydroxystannate with outstanding activity could be promisingly used in the future photocatalytic application.

Protein ubiquitination is a crucial component of the DNA damage response. To study the mechanism of the DNA damage-induced ubiquitination pathway, we analyzed the impact of the loss of two E3 ubiquitin ligases, RNF8 and Chfr. Notably, DNA damage-induced activation of ATM kinase is suppressed in cells deficient in both RNF8 and Chfr (double-knockout, or DKO), and DKO mice develop thymic lymphomas that are nearly diploid but harbor clonal chromosome translocations. Moreover, DKO mice and cells are hypersensitive to ionizing radiation. We present evidence that RNF8 and Chfr synergistically regulate histone ubiquitination to control histone H4 Lys16 acetylation through MRG15-dependent acetyltransferase complexes. Through these complexes, RNF8 and Chfr affect chromatin relaxation and modulate ATM activation and DNA damage response pathways. Collectively, our findings demonstrate that two chromatin-remodeling factors, RNF8 and Chfr, function together to activate ATM and maintain genomic stability in vivo.

As contemporary very large scale integration designs grow in complexity, design debugging has rapidly established itself as one of the largest bottlenecks in the design cycle today. Automated debug solutions such as those based on Boolean satisfiability (SAT) enable engineers to reduce the debug effort by localizing possible error sources in the design. Unfortunately, adaptation of these techniques to industrial designs is still limited by the performance and capacity of the underlying engines. This paper presents a novel formulation of the debugging problem using MaxSAT to improve the performance and applicability of automated debuggers. Our technique not only identifies errors in the design but also indicates when the bug is excited in the error trace. MaxSAT allows for a simpler formulation of the debugging problem, reducing the problem size by 80% compared to a conventional SAT-based technique. Empirical results demonstrate the effectiveness of the proposed formulation as run-time improvements of 4.5 × are observed on average. This paper introduces two performance improvements to further reduce the time required to find all error sources within the design by an order of magnitude.