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An Intuitionistic Fuzzy - Combined Weight - Mahalanobis distance - Multiple Attribute Decision Making (IFCM-MADM) method is proposed to solve comprehensive evaluation problem of the pollution control technologies for non-point sources in planting industry. The method is able to achieve cooperative improvement of the traditional TOPSIS on quantitative transformation of qualitative data in the evaluation indices by integrated intuitionistic fuzzy theory, subjective–objective combination weight calculation for the evaluation indicators by coupling the AHP and entropy weighting method, and accurately calculation on the distance between the evaluation object and the positive/negative solution by introducing the Mahalanobis distance to avoid the impact of correlation between indicators. Then, 34 typical technologies for agricultural non-point source pollution control selected from Major Science and Technology Program for Water Pollution Control and Treatment (MSTPWPCT) in China are employed for case application and validation, and the evaluation result obtained by IFCM- MADM has been deeply analyzed by comparing with the recommendation technologies provided by MSTPWPCT and the other two evaluation methods. The result shows that, the IFCM- MADM method can provide a scientific evaluation and selection of the technologies with high comprehensive benefits (including economic benefits, environmental benefits, and technical performance), which is highly consistent with the recommendation result from MSTPWPCT, and is capable to weaken the disadvantage of the objective weighting method and subjective weighting method, to a certain extent. The proposal of IFCM-MADM is the first attempt to enhance the traditional TOPSIS by extending its abilities on quantitative data processing, index weight calculation and accurate calculation of relative closeness, concurrently, and the method is also appropriate to other practical environmental evaluation problems with high complexity and multiple attributes. [ABSTRACT FROM AUTHOR]

It has relatively been difficult to accurately correlateand predictvapor–liquid equilibrium (VLE) data for the strongly associatingsystem containing the carboxyl acid due to its monomer undergoingpartial dimerization and even higher polymerization in the vapor andliquid phases. Herein, this paper reports that the formation statefor the associating component mainly has been the existence of dimerin the vapor and liquid phases through the geometric structures ofethanoic acid investigated theoretically with density functional theory(DFT), and the VLE data for the associating ternary system ethanal+ ethanol + ethanoic acid and the three constituent binary systemswere measured using a recirculating still at 101.325 kPa. Marek’schemical theory was considered due to the associating species as thedimer existence in the both phases. The three experimental binarydata sets were independently correlated using nonrandom two-liquid(NRTL), Wilson, and universal quasichemical activity coefficient (UNIQUAC)model, respectively, and the binary parameters were applied to predictthe VLE data for ternary system without any additional adjustment.By comparison with the measured values, the ternary equilibrium valuespredicted agreed well with the measured values in this way. The thermodynamicconsistency of the experimental VLE data was checked out by meansof the Wisniak’s L–Wtest for the binary systems and the Wisniak–Tamir’smodification of McDermott–Ellis test for the ternary system,respectively. [ABSTRACT FROM AUTHOR]

Summary Aberrant Skp2 signaling has been implicated as a driving event in tumorigenesis. Although the underlying molecular mechanisms remain elusive, cytoplasmic Skp2 correlates with more aggressive forms of breast and prostate cancers. Here, we report that Skp2 is acetylated by p300 at K68 and K71, which is a process that can be antagonized by the SIRT3 deacetylase. Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to increased Skp2 stability through impairment of the Cdh1-mediated proteolysis pathway. As a result, Skp2 oncogenic function is increased, whereby cells expressing an acetylation-mimetic mutant display enhanced cellular proliferation and tumorigenesis in vivo. Moreover, acetylation of Skp2 in the nuclear localization signal (NLS) promotes its cytoplasmic retention, and cytoplasmic Skp2 enhances cellular migration through ubiquitination and destruction of E-cadherin. Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer is the most frequently diagnosed tumor in men and the second most common cause of cancer-related death for males in the United States. It has been shown that multiple signaling pathways are involved in the pathogenesis of prostate cancer, such as androgen receptor (AR), Akt, Wnt, Hedgehog (Hh) and Notch. Recently, burgeoning amounts of evidence have implicated that the F-box protein Skp2 (S-phase kinase associated protein 2), a well-characterized oncoprotein, also plays a critical role in the development and progression of prostate cancer. Therefore, this review discusses the recent literature regarding the function and regulation of Skp2 in the pathogenesis of prostate cancer. Furthermore, we highlight that Skp2 may represent an attractive therapeutic target, thus warrants further development of agents to target Skp2, which could have significant therapeutic impact on prostate cancer. [Copyright &y& Elsevier]

Summary: The activities of both mTORC1 and mTORC2 are negatively regulated by their endogenous inhibitor, DEPTOR. As such, the abundance of DEPTOR is a critical determinant in the activity status of the mTOR network. DEPTOR stability is governed by the 26S-proteasome through a largely unknown mechanism. Here we describe an mTOR-dependent phosphorylation-driven pathway for DEPTOR destruction via SCFβTrCP. DEPTOR phosphorylation by mTOR in response to growth signals, and in collaboration with casein kinase I (CKI), generates a phosphodegron that binds βTrCP. Failure to degrade DEPTOR through either degron mutation or βTrCP depletion leads to reduced mTOR activity, reduced S6 kinase activity, and activation of autophagy to reduce cell growth. This work expands the current understanding of mTOR regulation by revealing a positive feedback loop involving mTOR and CKI-dependent turnover of its inhibitor, DEPTOR, suggesting that misregulation of the DEPTOR destruction pathway might contribute to aberrant activation of mTOR in disease. [Copyright &y& Elsevier]

Summary: The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s) remain largely unknown. Here, we report that Rictor associates with Cullin-1 to form a functional E3 ubiquitin ligase. Rictor, but not Raptor or mTOR alone, promotes SGK1 ubiquitination. Loss of Rictor/Cullin-1-mediated ubiquitination leads to increased SGK1 protein levels as detected in Rictor null cells. Moreover, as part of a feedback mechanism, phosphorylation of Rictor at T1135 by multiple AGC kinases disrupts the interaction between Rictor and Cullin-1 to impair SGK1 ubiquitination. These findings indicate that the Rictor/Cullin-1 E3 ligase activity is regulated by a specific signal relay cascade and that misregulation of this mechanism may contribute to the frequent overexpression of SGK1 in various human cancers. [Copyright &y& Elsevier]

Deregulated Skp2 function promotes cell transformation, and this is consistent with observations of Skp2 overexpression in many human cancers. However, the mechanisms underlying elevated Skp2 expression are still unknown. Here we show that the serine/threonine protein kinase Akt1, but not Akt2, directly controls Skp2 stability by a mechanism that involves degradation by the APC–Cdh1 ubiquitin ligase complex. We show further that Akt1 phosphorylates Skp2 at Ser 72, which is required to disrupt the interaction between Cdh1 and Skp2. In addition, we show that Ser 72 is localized within a putative nuclear localization sequence and that phosphorylation of Ser 72 by Akt leads to cytoplasmic translocation of Skp2. This finding expands our knowledge of how specific signalling kinase cascades influence proteolysis governed by APC–Cdh1 complexes, and provides evidence that elevated Akt activity and cytoplasmic Skp2 expression may be causative for cancer progression. [ABSTRACT FROM AUTHOR]

Abstract: Interferon (IFN) regulatory factors (IRFs) are a family of transcription mediators involved in the regulation of type I IFN (IFN-α/β) transcription. Among the nine already identified IRFs, IRF-3 is a constitutively and ubiquitously expressed and plays a critical role in the transcriptional activation of type I IFN and IFN-stimulated genes including IFN-α1, IFN-β and RANTES. In the present study, we report the identification of a novel alternatively spliced transcript of murine Irf-3 gene (mIrf-3) designated mIRF-3a. mIRF-3a is ubiquitously present in mouse tissues along with mIRF-3 and could be translocated into the nucleus in uninfected L929 cells. EMSA and reporter assay demonstrated that mIRF-3a binds to ISRE sequences in murine Ifn-β promoter and represses Ifn-β promoter activation induced by Newcastle disease virus infection. These results suggest that mIRF-3a may act as a modulator of mIRF-3 functions in vivo. [Copyright &y& Elsevier]

Abstract: The construction of experimental advanced superconducting Tokamak (EAST) was completed at the Institute of Plasma Physics of Chinese Academy of Sciences (CASIPP) in January of 2006 after challenging techniques over the period of 8 years. The followed cooling-down test was also successfully performed and all superconducting magnets including two current leads and seven bus lines entered the cryogenic superconducting state smoothly. Total 260 shots have been fired. The longest TF current duration was 5000s and the highest TF current was 8200A (2T). All the testing results showed that the EAST machine and its sub-systems have been successfully built. EAST machine is a fully superconducting Tokamak. It consists of more 20,000 parts and possesses the configuration of 7600mm in diameter, 6600mm in height and the weight of 400tonnes. The complicated general assembly of EAST began in July of 2003 and nearly took two and half years. During the process, not only a series of common difficulties for a large Tokamak but also many technique problems for a superconducting Tokamak itself needed to be solved properly. This paper emphasizes on some key technology issues that were faced and solved in EAST assembly process including optimization of assembly procedure, survey and alignment, ensuring of thermal insulation gap, installation of unique parts, treatment of electric insulation, improvement on heat conduction, control on deformation of vacuum vessel, etc. Besides, the quality control (QC), which made important contributions to the general assembly is also described. [Copyright &y& Elsevier]

In this paper, we report a simple polypeptide-directed strategy for fabricating large spherical assembly of CaCO3 nanoparticles. Stepwise growth and assembly of a large number of nanoparticles have been observed, from the formation of an amorphous liquidlike CaCO3-polypeptide precursor, to the crystallization and stabilization of polypeptide-capped nanoparticles, and eventually, the spherical assembly of nanoparticles. The "soft" poly(aspartate)-capping layer binding on a nanoparticle surface resulted in the unusual soft nature of nanoparticle assembly, providing a reservoir of primary nanoparticles with a moderate mobility, which is the basis of a new strategy for reconstructing nanoparticle assembly into complex nanoparticle architectures. Moreover, the findings of the secondary assembly of nanoparticle microspheres and the morphology transformation of nanoparticle assembly demonstrate a flexible and controllable pathway for manipulating the shapes and structures of nanoparticle assembly. In addition, the combination of the polypeptide with a double hydrophilic block copolymer (DHBC) allows it to possibly further control the shape and complexity of the nanoparticle assembly. A clear perspective is shown here that more complex nanoparticle materials could be created by using "soft" biological proteins or peptides as a mediating template at the organic−inorganic interface. [ABSTRACT FROM AUTHOR]

• Epoxy coating modified by hydrophobic nano-silica was fabricated via physical blending. • The modified epoxy coating presented good thermal stability at the temperature of 250 °C. • The addition of hydrophobic nano-silica improved the water repellency of modified epoxy coating. • The modified epoxy coating with the most hydrophobic nano-silica exhibited the best corrosion protection performance. • Both traditional epoxy coating and modified epoxy coating showed good adhesion to phosphatized Q235 carbon steel substrates. Corrosion existing in many fields brings lots of troubles to our life. In this work, epoxy coatings modified by hydrophobic nano-silica and hydrophilic nano-silica were fabricated to provide corrosion protection for phosphatized Q235 carbon steel. The traditional epoxy coating was prepared by the polymerization of trimethylolpropane triglycidyl ether and diethylenetriamine. The modified epoxy coating was fabricated by the polymerization and mixing of trimethylolpropane triglycidyl ether, diethylenetriamine and nano-silica. The microscopic morphologies of various epoxy coatings were investigated by SEM. Wettability of epoxy coatings was measured by static contact angle measurement instrument. Thermal stability was tested by thermo gravimetric analyzer. Corrosion behaviors was investigated by electrochemical workstation. Adhesion was reflected by cross-cut test and pull-off test. Equivalent circuits were used to fit the electrochemical impedance spectrum (EIS). According to experimental results, modified epoxy coatings present good hydrophobicity, good thermal stability at 250 °C with only about 3 % weight loss and the ca. 10 μm modified epoxy coating added with the most hydrophobic nano-silica shows the best anticorrosive performance with impedance of 5.25 × 105 Ω•cm2 (0.01 Hz) at 0 h immersion. The anticorrosive performance of epoxy coating is significantly improved when hydrophobic nano-silica is added into epoxy matrix. Adding hydrophobic nano-silica can effectively prolong the diffusion path of water-soluble corrosive medium and the hydrophobicity is able to retard the diffusion of water. [ABSTRACT FROM AUTHOR]

Highlights • Eight (five free and seven bound) HAs at levels up to hundreds of ng/g were detected in sausage. • Smoking could increase HAs to more than twice levels found in baked sausages. • At higher baking temperatures, lower levels of HAs were found in baked sausages. • At higher smoking temperatures, higher levels of HAs were found in smoked sausages. • The highest total HAs was 422 ± 17.5 ng/g in sausages smoked at 60 °C. Abstract We used an UPLC-MS/MS method to investigate the effects of smoking or baking on the formation of heterocyclic amines (HAs) in sausage processing. We used principal component analysis (PCA) to differentiate the chemical composition, pH and colour of the processed sausages. We detected and quantified eight types of HAs (PhIP, DMIP, Phe-P-1, IQ[4,5- b ], 7,8-DiMeIQx, AαC, harman and norharman) in sausages, finding total HA concentrations as high as 422 ± 17.5 ng/g. Higher smoking temperatures led to higher concentrations of total HA in smoked sausages (330 ± 8.19 to 422 ± 17.5 ng/g). On the contrary, higher baking temperatures created lower total HA concentrations in baked sausages (ranging from 139 ± 9.83 to 306 ± 0.92 ng/g). Our results demonstrated that HAs are produced even at low temperatures, which means that HAs should be controlled during sausage processing to minimise their formation. [ABSTRACT FROM AUTHOR]

Background: UTX (encoded by KDM6A), a histone demethylase for H3K27me2/3, is frequently mutated in human cancers. However, its functional and regulatory mechanisms in colorectal cancer (CRC) remain unclear. Methods: Immunohistochemistry staining was used to investigate the clinical relevance of UTX in CRC. Additionally, we generated a spontaneous mouse CRC model with conditional Utx knockout to explore the role of UTX in the colorectal tumorigenesis. Post-translational regulation of UTX was determined by co-immunoprecipitation and immunoblot analyses. Results: Herein, we identify that downregulation of UTX, mediated by the Cullin 4B-DNA Damage Binding Protein-1-Constitutive Photomorphogenesis Protein 1 (CUL4B-DDB1-COP1) complex, promotes CRC progression. Utx deletion in intestinal epithelial cells enhanced the susceptibility to tumorigenesis in AOM/DSS-induced spontaneous mouse CRC model. However, this effect is primarily alleviated by GSK126, an inhibitor of histone methyltransferase EZH2. Mechanistically, EMP1 and AUTS2 are identified as putative UTX target genes mediating UTX functions in limiting intestinal tumorigenesis. Notably, the CUL4B-DDB1-COP1 complex is identified as the functional E3 ligase responsible for targeting UTX for degradation in CRC cells. Thus, Cop1 deficiency in mouse intestinal tissue results in UTX accumulation and restricts tumorigenesis. Furthermore, patient cohort analysis reveals that UTX expression is negatively correlated with clinical stage, favorable disease outcomes, and COP1 expression. Conclusions: In the current study, the tumor suppressor function and regulation of UTX in CRC provide a molecular basis and the rationale to target EZH2 in UTX-deficient CRC. [ABSTRACT FROM AUTHOR]

Normal adjacent tissues (NATs) of hepatocellular carcinoma (HCC) differ from healthy liver tissues and their heterogeneity may contain biological information associated with disease occurrence and clinical outcome that has yet to be fully evaluated at the proteomic level. This study provides a detailed description of the heterogeneity of NATs and the differences between NATs and healthy livers and revealed that molecular features of tumor subgroups in HCC were partially reflected in their respective NATs. Proteomic data classified HCC NATs into two subtypes (Subtypes 1 and 2), and Subtype 2 was associated with poor prognosis and high-risk recurrence. The pathway and immune features of these two subtypes were characterized. Proteomic differences between the two NAT subtypes and healthy liver tissues were further investigated using data-independent acquisition mass spectrometry, revealing the early molecular alterations associated with the progression from healthy livers to NATs. This study provides a high-quality resource for HCC researchers and clinicians and may significantly expand the knowledge of tumor NATs to eventually benefit clinical practice. [ABSTRACT FROM AUTHOR]

The simultaneous achievement of large surface areas and high IL contents in porous materials are highly beneficial for efficient carbon dioxide (CO2) capture and atmospheric fixation. Herein, a series of porous hypercrosslinked poly(ionic liquid)s (HPILs) are successfully developed through a two-step synthetic strategy, including free radical self-polymerization of a specific benzyl bromide-tethered imidazole ionic liquid (IL) to fabricate a linear PIL as a precursor, and a subsequent Friedel–Crafts alkylation between the precursor and the crosslinker for hypercrosslinking. The HPILs featured large surface areas of up to 855 m2 g−1 along with a hierarchically nanoporous structure, high IL contents (2.19–2.91 mmol g−1) and satisfactory CO2-philic properties. By virtue of the combined advantages, HPILs served as metal-free heterogeneous catalysts for solvent-additive-free CO2 cycloaddition with epichlorohydrin at 80 °C and 0.1 MPa CO2 for 24 h, presenting high catalytic activity and stable reusability. A high yield of 99.0% coupled with a turnover frequency (TOF) of 6.0 h−1 was achieved, much higher than most of the reported metal-free heterogeneous catalysts, even superior to homogeneous analogues. Furthermore, various epoxides, including large-sized epoxides, were effectively converted into carbonates with high yields, affording good substrate applicability. This work reports a facile and universal approach for the construction of porous HPILs with both great porosities and high IL contents towards efficient chemical fixation of CO2 under mild conditions. [ABSTRACT FROM AUTHOR]

Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org , form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development. [Display omitted] • Integrating tumor proteogenomics with cell line data reveals pan-cancer druggable targets • Proteogenomic discovery of synthetic lethality facilitates targeting tumor suppressor loss • Computational workflows enable effective tumor antigen identification • Web portal provides access to identified targets and their supporting data Integrating pan-cancer proteogenomic data from 1,043 patients across 10 cancer types, genetic screen data from cell lines, and tumor antigen predictions unveils a comprehensive landscape of protein and peptide targets for drug repurposing and therapy development. [ABSTRACT FROM AUTHOR]

Summary: The APC/Cdh1 E3 ubiquitin ligase plays an essential role in both mitotic exit and G1/S transition by targeting key cell-cycle regulators for destruction. There is mounting evidence indicating that Cdh1 has other functions in addition to cell-cycle regulation. However, it remains unclear whether these additional functions depend on its E3 ligase activity. Here, we report that Cdh1, but not Cdc20, promotes the E3 ligase activity of Smurf1. This is mediated by disruption of an autoinhibitory Smurf1 homodimer and is independent of APC/Cdh1 E3 ligase activity. As a result, depletion of Cdh1 leads to reduced Smurf1 activity and subsequent activation of multiple downstream targets, including the MEKK2 signaling pathway, inducing osteoblast differentiation. Our studies uncover a cell-cycle-independent function of Cdh1, establishing Cdh1 as an upstream component that governs Smurf1 activity. They further suggest that modulation of Cdh1 is a potential therapeutic option for treatment of osteoporosis. [Copyright &y& Elsevier]

The article highlights the new functional aspects of F-box and WD repeat domain-containing 7 (FBW7) tumor suppressor in drug resistance. It summarizes the function of FBW7 in the observed drug resistance and how targeting FBW7 can help design new therapeutic strategies that will improve drug sensitivity and achieve better treatment outcomes. It suggests that designing specific inhibitors to FBW7 downstream targets may be a viable therapeutic approach.

Summary: Mdm2 is the major negative regulator of the p53 pathway. Here, we report that Mdm2 is rapidly degraded after DNA damage and that phosphorylation of Mdm2 by casein kinase I (CKI) at multiple sites triggers its interaction with, and subsequent ubiquitination and destruction, by SCFβ-TRCP. Inactivation of either β-TRCP or CKI results in accumulation of Mdm2 and decreased p53 activity, and resistance to apoptosis induced by DNA damaging agents. Moreover, SCFβ-TRCP-dependent Mdm2 turnover also contributes to the control of repeated p53 pulses in response to persistent DNA damage. Our results provide insight into the signaling pathways controlling Mdm2 destruction and further suggest that compromised regulation of Mdm2 results in attenuated p53 activity, thereby facilitating tumor progression. [ABSTRACT FROM AUTHOR]

Vacuum leak is a critical issue for all devices having vacuum system, especially for the large complex experimental facilities. They often have vacuum components integrated which are inaccessible once the assembly was finished. Therefore, if any unacceptable vacuum leaks occur on the cooling/baking channels of the vacuum components, the machine, at least partially, needs to be disassembled before the maintenance, which would cause extensive experimental program downtime and financial costs. An innovative remote sealing method has been studied to permanently repair such vacuum leaks by injecting a sealant called KH-1714 into the channels with pressurized inert gas. Three experiments, that at 10–20 m away sealing different types of leaked components (bellows, circular pipe or rectangle pipe) with leak rates at the level of 10 −6 –10 −5 Pa m 3 /s, were done to study the feasibility and reliability of the method. The details of the experiments and results were presented and discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Review of lignin dissociation to provide guidance for the use of lignocellulose. • The advantages and disadvantages of each depolymerization method are summarized. • The contribution made by lignin depolymerization to sugar biorefinery is discussed. The biorefining of sugar-based biomass has attracted increasing attention in response to the continuous depletion of fossil fuel reserves. The key to biorefinery is to choose a suitable way to pretreat lignocellulose to depolymerise lignin, thus releasing cellulose and hemicellulose, and the monosaccharides produced by subsequent enzymatic saccharification can be converted into high value-added compounds by biological or chemical methods, and lignin and its derivatives can also be used in the production of other biopolymers. Currently, numerous scholars have studied and developed processes for lignin depolymerisation. Still, the catalytic depolymerisation of lignin is complex, and the catalytic depolymerisation mechanism and the evolution of the chemical bonding still need to be determined. In this paper, we expect to classify the existing lignin depolymerisation methods and mechanisms reported in the literature and evaluate the advantages and disadvantages of each technique, as well as review the potential applications and challenges of lignin and its derivatives in the production of biopolymers, with the expectation of providing theoretical and technological support for the research and development of new efficient and stable lignin depolymerisation methods, and contributing to the development of biorefinery technology for lignocellulosic resources. [ABSTRACT FROM AUTHOR]

Wnt/β-catenin signaling is a conserved pathway crucially governing development, homeostasis, and oncogenesis. Discoveries of its regulators hold great values in both basic and translational research. Through screening, we identified a deubiquitinase, USP10, as a critical modulator of β-catenin. Mechanistically, USP10 binds to key scaffold Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination. Surprisingly, USP10 physically tethers Axin1 and β-catenin and promotes the phase separation for β-catenin suppression regardless of the enzymatic activity. Function-wise, USP10 enzymatic activity preferably regulates embryonic development and both the enzymatic activity and physical function jointly control intestinal homeostasis by antagonizing β-catenin. In colorectal cancer, USP10 substantially represses cancer growth mainly through physical promotion of phase separation and correlates with Wnt/β-catenin magnitude clinically. Collectively, we discovered USP10 functioning in multiple biological processes against β-catenin and unearthed the enzyme-dependent and -independent "dual-regulating" mechanism. These two functions of USP10 work in parallel and are context dependent. [Display omitted] • USP10 acts as a suppressor of Wnt/β-catenin signaling • USP10 stabilizes Axin1 via K48-linked deubiquitination • USP10 promotes phase separation to inhibit β-catenin regardless of DUB activity • The DUB-dependent and -independent paths work in parallel and are context dependent Wang et al. discovered USP10 as a suppressor of Wnt/β-catenin signaling. USP10 stabilizes the key scaffold protein Axin1 through DUB activity and facilitates the liquid-liquid phase separation to constrain β-catenin physically. The enzymatic-dependent and -independent functions work in parallel and are context dependent, thus presenting a prototype of protein functioning. [ABSTRACT FROM AUTHOR]

The effect of soy protein isolate and its hydrolysates on ice cream mix stability and melt-down properties of ice cream were investigated. Ice creams were made with 10% milk fat, 3.5% protein and 34.3% total solids, and all contained 0.15% added monoglycerides. The proteins used were native soy protein isolate (NSPI), commercial soy proteins isolate (CSPI), soy protein hydrolyzed by pepsin (SPHPe), soy protein hydrolyzed by papain (SPHPa) and skim milk powder (SMP). Ice cream with SPHPe containing the highest relative composition of β-subunit showed good mix emulsion stability and rapid melting rate because β-subunit cannot be displaced by the monoglycerides, leading to lack of fat partial coalescence in the ice cream. SPHPa ice cream exhibited comparable functionality to SMP in rheological and meltdown properties. SDS-PAGE results indicated that α subunit, α′ subunit, acidic subunit, basic subunit and small molecule polypeptide were displaced by monoglycerides during ice cream aging. Selective hydrolysis of soy protein can be used for ice cream with sufficient fat partial coalescence and good melt-down rates. Image 1 • Selective hydrolysis led to hydrolysates with the different polypeptide profile. • The interaction between SPI subunits and monoglycerides decided meltdown properties. • SPHPe ice cream shows insufficient fat partial-coalescence and rapid melting rate. • Ice cream with SPHPa exhibited the similar melting properties as milk protein. [ABSTRACT FROM AUTHOR]

Summary: A natural colourant derived from purple‐fleshed sweet potato (PFSP) by ultrasound‐assisted solvent extraction was examined in terms of its anthocyanins and 6‐month storage stability under different conditions: avoid from light at 25 (AL25) and 37 °C (AL37) and under fluorescent light at 25 °C (FL25). This PFSP colourant mainly contained the following peonidin anthocyanins: peonidin 3‐p‐hydroxybenzoyl sophoroside‐5‐glucoside, peonidin 3‐feruloyl sophoroside‐5‐glucoside, peonidin 3‐caffeoyl sophoroside‐5‐glucoside, peonidin dicaffeoyl sophoroside‐5‐glucoside, peonidin 3‐caffeoyl‐p‐hydroxybenzoyl sophoroside‐5‐glucoside and peonidin caffeoyl‐feruloyl sophoroside‐5‐glucoside. The degradation ratios of PFSP anthocyanins (PFSPAs) under AL25, AL37 and FL25 were around 50.7%, 89.0% and 87.0% respectively. The FL25 and AL37 conditions had similar effects on the colourant's total colour change (ΔEab). The degradation kinetics followed the zero‐order reaction models. The PFSPAs were more stable during storage than other anthocyanins because they mainly consist of di‐acylated and double glycosylated forms of peonidin derivatives. These results may promote the application of PFSPAs as a novel natural colourant in food industry. [ABSTRACT FROM AUTHOR]

This study selected common processing methods for orthodox black tea and investigated changes in the levels of N ε -(carboxymethyl)lysine (CML), N ε -(carboxyethyl)lysine (CEL), lysine, and polyphenols during each processing stage and using different parameters of each processing step. The effects of epicatechin gallate, epigallocatechin, epigallocatechin gallate, and gallic acid on the levels of CML, CEL, fructoselysine, glyoxal, and methylglyoxal were investigated by chemical model systems study under black tea processing conditions. In tea samples, CML and CEL levels significantly increased during drying (could reach 51.8 and 8.7 μg/g tea, respectively), while natural withering and extensive rolling and fermentation times facilitated the formation of CML and CEL by altering the substrate concentrations and the cellular structure of tea leaves to be dried. The results of model systems (containing lysine, glucose, and fructose) indicated that polyphenols were able to enhance the production of CML and CEL, and the levels of CML and CEL increased 1.2–3.2- and 1.6–3.5-fold, respectively. Furthermore, the main pathways responsible for CML and CEL formation during black tea processing likely involve fructoselysine and others but not glyoxal or methylglyoxal. Unlabelled Image • CML and CEL were mainly formed during the drying of black tea processing. • Natural withering led to more CML/CEL formed in the final tea product than mechanical withering. • Long rolling and fermentation time facilitated the formation of CML and CEL. • Catechins and gallic acid facilitated CML and CEL formation in lysine + sugar model. • The main pathway of CML/CEL formation was not through α-dicarbonyls in a tea model. [ABSTRACT FROM AUTHOR]

• β-subunits, acidic and basic subunits contribute to solid-like properties of layer. • The mixed monolayers with protein and monoglycerides are formed in all samples. • The presence of monoglycerides reduces the amount of adsorbed protein. • Monoglycerides displace most subunits from the fat droplets except β-subunit. The effect of the adsorption behavior of soy proteins hydrolysates and monoglycerides on the properties of the film at oil-water interfaces in emulsions and emulsion stability was investigated. Surface tension, adsorbed protein composition and interfacial rheological properties were measured to gain insights into the relationships between molecular composition and properties. The interfacial film formed by 7S (β-conglycinin), 11S (Glycinin) and native soy protein isolate (NSPI) exhibited high elasticity due to a high concentration of adsorbed β-subunits, acidic and basic subunits. Soy protein isolate hydrolyzed by pepsin (SPHPe) and soy protein isolate hydrolyzed by papain (SPHPa) had a high percentage of small peptides, less β-subunits and acidic subunits, forming a fluid-like interfacial film at the beginning of the time sweep. Commercial soy protein isolate (CSPI) film without main soy protein subunits induced fluid-like properties. Monoglycerides displaced the small peptides, acidic and basic subunits from the interface and led to fat globule destabilization after 24 h aging. Emulsions were stable with 7S and SPHPe with high proportion of β-subunits, which were not replaced by monoglycerides. This study provided the foundation for the preparation and application of soy protein isolate with different emulsion stability requirements paired with selected enzyme treatments. [ABSTRACT FROM AUTHOR]

Herein, a nitrogen-doped graphene (NPGR) with amphiphilic surface was efficiently synthesized by radio-frequency cold plasma under low vacuum, using ammonia as plasma source. NPGR supported platinum nanocatalyst (Pt/NPGR) was then prepared for aqueous-phase hydrogenation of cinnamaldehyde (CAL) and effects of nitrogen doping on the reaction were investigated. Results indicated the formation of a Pickering emulsion catalytic system, exhibiting the high catalytic performance. Apparent initial reaction rate constant (k) over it arrived at 1.07 h−1, higher than that over Pt catalysts supported on pristine graphene (Pt/ GR, 0.62 h−1) and graphene oxide (Pt/GO, 0.15 h−1), respectively. On the other hand, the selectivity to cinnamyl alcohol kept high (84%) at 95% CAL conversion. In addition, the catalyst showed good recyclability for the reaction. The high catalytic performance of Pt/NPGR in aqueous-phase CAL hydrogenation was thanks to the enhanced surface properties of graphene after doping a small amount of nitrogen in it. [Display omitted] • Nitrogen-doped graphene (NPGR) was efficiently synthesized by ammonia cold plasma. • NPGR possessed amphiphilic surface. • Pt/NPGR stabilized Pickering emulsion catalytic system formed in aqueous-phase hydrogenation of cinnamaldehyde. • It exhibited the high catalytic performance thanks to the enhanced surface properties. [ABSTRACT FROM AUTHOR]

PTEN is one of the most frequently mutated tumour suppressors and reduction in PTEN protein stability also plays a role in tumorigenesis. Although several ubiquitin ligases for PTEN have been identified, the deubiquitylase for de-polyubiquitylation and stabilization of PTEN is less defined. Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN. Depletion of OTUD3 leads to the activation of Akt signalling, induction of cellular transformation and cancer metastasis. OTUD3 transgenic mice exhibit higher levels of the PTEN protein and are less prone to tumorigenesis. Reduction of OTUD3 expression, concomitant with decreased PTEN abundance, correlates with human breast cancer progression. Furthermore, we identified loss-of-function OTUD3 mutations in human cancers, which either abolish OTUD3 catalytic activity or attenuate the interaction with PTEN. These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression. [ABSTRACT FROM AUTHOR]

NiFe2O4nanoparticles have been synthesized by water-in-oil microemulsion method. Effects of calcination temperature varying from 600 to 1200°C on the structural and magnetic properties of NiFe2O4nanoparticles have been investigated. Studies carried out using XRD, SEM and VSM techniques. Results indicated that magnetic properties of NiFe2O4nanoparticles showed great dependence on the variation of the crystallinity and particle sizes caused by the calcination temperature. The crystallization, saturation magnetization Ms and remenant magnetization Mr increased as the calcination temperature increased. But the variation of coercivity Hc was not in accordance with that of Ms and Mr, indicating that Hc was not determined only by the crystallinity and size of NiFe2O4nanoparticles. [ABSTRACT FROM PUBLISHER]

Summary Deficiency in repair of damaged DNA leads to genomic instability and is closely associated with tumorigenesis. Most DNA double-strand-breaks (DSBs) are repaired by two major mechanisms, homologous-recombination (HR) and non-homologous-end-joining (NHEJ). Although Akt has been reported to suppress HR, its role in NHEJ remains elusive. Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF β-TRCP in a CKI-dependent manner. Physiologically, upon DNA damage, XLF-T181E expressing cells display impaired NHEJ and elevated cell death. Whereas a cancer-patient-derived XLF-R178Q mutant, deficient in XLF-T181 phosphorylation, exhibits an elevated tolerance of DNA damage. Together, our results reveal a pivotal role for Akt in suppressing NHEJ and highlight the tight connection between aberrant Akt hyper-activation and deficiency in timely DSB repair, leading to genomic instability and tumorigenesis. [ABSTRACT FROM AUTHOR]

Ferrite is an important ceramic material with magnetic properties that are useful in many types of electronic devices. In this paper we synthesized nanostructured Ni0.7Zn0.3Fe2O4and Mn0.7Zn0.3Fe2O4with spinel structure in the system of water-in-oil microemulsion of water/Triton X–100/n-hexanol/cyclohexane. The result showed that nanoparticles with size in the range of 50–80 nm could be obtained by microemulsion method. FT-IR spectrum, XRD patterns and DTA curves revealed that the nanoparticles could be obtained via calcining its precursor at 500°C. The VSM plots showed that the ferrimagnetic behavior was expected for this type of magnetic material. [ABSTRACT FROM AUTHOR]

Akt, also known as protein kinase B, plays key roles in cell proliferation, survival and metabolism. Akt hyperactivation contributes to many pathophysiological conditions, including human cancers, and is closely associated with poor prognosis and chemo- or radiotherapeutic resistance. Phosphorylation of Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear whether further mechanisms account for full Akt activation, and whether Akt hyperactivation is linked to misregulated cell cycle progression, another cancer hallmark. Here we report that Akt activity fluctuates across the cell cycle, mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479 at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promotes Akt activation through facilitating, or functionally compensating for, S473 phosphorylation. Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably, cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2 in governing Akt activation. Together, the results of our study show Akt S477/T479 phosphorylation to be an essential layer of the Akt activation mechanism to regulate its physiological functions, thereby providing a new mechanistic link between aberrant cell cycle progression and Akt hyperactivation in cancer. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin (mTOR) functions as a critical regulator of cellular growth and metabolism by forming multi-component, yet functionally distinct complexes mTORC1 and mTORC2. Although mTORC2 has been implicated in mTORC1 activation, little is known about how mTORC2 is regulated. Here we report that phosphorylation of Sin1 at Thr 86 and Thr 398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2. Importantly, Sin1 phosphorylation, triggered by S6K or Akt, in a cellular context-dependent manner, inhibits not only insulin- or IGF-1-mediated, but also PDGF- or EGF-induced Akt phosphorylation by mTORC2, demonstrating a negative regulation of mTORC2 independent of IRS-1 and Grb10. Finally, a cancer-patient-derived Sin1-R81T mutation impairs Sin1 phosphorylation, leading to hyper-activation of mTORC2 by bypassing this negative regulation. Together, our results reveal a Sin1-phosphorylation-dependent mTORC2 regulation, providing a potential molecular mechanism by which mutations in the mTORC1-S6K-Sin1 signalling axis might cause aberrant hyper-activation of the mTORC2-Akt pathway, which facilitates tumorigenesis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Several rounds insulation trials for ITER Feeder joint were carried out in ASIPP. [•] Wet-winding, VPI were practiced and attempt for the best impregnation strategy. [•] Improvement of wet-winding technology with vacuum assistance was realized. [•] To supplement the electrical test, DR technology was explored for insulation quality inspection. [Copyright &y& Elsevier]

Abstract: The human hepatitis B virus enhancer II B1 binding factor (hB1F), which regulates the expression of hepatitis B virus genes, is identified as a nuclear receptor. It regulates several liver-specific genes and plays an important role in the bile acid biosynthesis pathway. A significantly optimized protocol has been worked out to prepare 15N and/or 13C-labeled hB1F ligand-binding domain in minimal medium with high yields for NMR studies. Under the various conditions optimized for the purification of His6-hB1F ligand-binding domain, the yield of the purified protein is estimated to be 25–30mg from 0.5L of M9 minimal media. Electrospray ionization mass spectrometry data confirm the correctness of the primary sequence. Dynamic light scattering experiment proves that the protein exists as a monomeric form. In addition, the circular dichroism results show that the protein has a well-regulated secondary structure and a high α-helical content in ammonium bicarbonate buffer at 20°C and pH 7.4. Finally, uniformly 15N-labeled protein is characterized by a TROSY–HSQC spectrum, and the dispersion of 15N–1H cross-peaks in the spectrum indicates the presence of well-ordered and properly folded protein as a monomer. [Copyright &y& Elsevier]

• N‑heterocyclic carbene-CO 2 (NHC-CO 2) adducts embedded nanoporous polymers are prepared. • NHC-CO 2 adducts is formed via a facile and green strategy without using any base. • The polymers serve as halogen-free heterogeneous catalyst for atmospheric CO 2 fixation. • Highly catalytic activity, good recyclability and substrate compatibility are achieved. • Appropriate proportion of NHC-CO 2 adducts in porous skeleton accounts for good performance. A serial of porous polymers incorporating N‑heterocyclic carbene-CO 2 adducts (designated as NHC-CO 2 adducts) were facilely synthesized via radical polymerization of N-vinylimidazolate and ethyleneglycol dimethacrylate plus post-treatment with dimethyl carbonate (DMC). The polymers possessed tunable chemical structure, large surface area along with abundant meso -macropores and enhanced CO 2 uptake which functioned as metal-halogen-free heterogeneous organocatalysts for solvent-free cycloaddition of CO 2 to styrene oxide under 10 bar CO 2 pressure, exhibiting highly catalytic activity and stable recyclability. Further, turnover frequency (TOF) of 7.1 h−1 (94.3% yield, 12 h) was obtainable under ambient condition, much higher than those of reported metal-halogen-free heterogeneous catalysts, even comparable with existing halogen-containing ones. Furthermore, the catalyst could efficiently convert various epoxides including internal epoxides into corresponding cyclic carbonates under mild condition (1 bar, 70–120 °C). The excellent catalytic performance was ascribed to the appropriate proportion of NHC-CO 2 adducts in porous skeleton structure triggered by DMC. A plausible reaction mechanism was proposed to understand NHC-catalyzed fixation of CO 2. This study highlights porous organic polymer is a versatile platform of NHC-CO 2 adducts to construct eco-friendly solid catalyst towards efficient CO 2 conversion. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional experiments revealed that XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. In addition, we found that the nuclear export of pre-miR-3184 was suppressed by SUMOylated XPO5. Moreover, PLCB1 was identified as the common target of miR-3184-5p and miR-3184-3p. The suppressed phenotype induced by miR-3184-5p and miR-3184-3p could be rescued by overexpression of PLCB1. Bioinformatics analysis showed that PLCB1 expression had a negative relationship with HCC patient survival. The inhibitory effects of MHCC97H cells resulted from abnormal XPO5 SUMO modification could be blocked by miR-3184 inhibitor or PLCB1 overexpression. In conclusion, our findings demonstrate a novel mechanism of XPO5 in HCC, that is, the SUMOylated XPO5 acts as an "oncogenic" role in MHCC97H cells proliferation, migration and invasion by controlling the nuclear-cytoplasm transportation of miR-3184, thus up-regulating PLCB1 expression. • XPO5 was highly expressed in HCC, which was associated with SUMO modification. • XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. • SUMOylated XPO5 regulates PLCB1 expression by controlling miR-3184 nucleo-cytoplasmic transport in HCC. [ABSTRACT FROM AUTHOR]