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Because of their ability to induce lymphocyte apoptosis, glucocorticoids (GC) are widely used to treat hematological malignancies such as lymphomas and multiple myeloma. Their effectiveness is often limited, however, due to the development of glucocorticoid resistance by a variety of molecular mechanisms. Here we performed an unbiased genome-wide CRISPR screen with the human T-cell leukemia cell line Jurkat to find previously unidentified genes required for GC-induced apoptosis. One such gene was KMT2D (also known as MLL2 or MLL4), which encodes a histone lysine methyltransferase whose mutations are associated with a variety of cancers, blood malignancies in particular, and are considered markers of poor prognosis. Knockout of KMT2D by CRISPR/Cas9 gene editing in Jurkat and several multiple myeloma cell lines downregulated GR protein expression. Surprisingly, this was not due to a reduction in GR transcripts, but rather to a decrease in the protein’s half-life, primarily due to proteasomal degradation. Reconstitution of KMT2D expression restored GR levels. In contrast to the known ability of KMT2D to control gene transcription through covalent histone methylation, KMT2D-mediated upregulation of GR levels did not require its methyltransferase activity. Co-immunoprecipitation and proximity ligation assays found constitutive binding of KMT2D to the GR, which was enhanced in the presence of GC. These observations reveal KMT2D to be essential for the stabilization of cellular GR levels, and suggest a possible mechanism by which KMT2D mutations may lead to GC resistance in some malignancies. [ABSTRACT FROM AUTHOR]

The efficient pyrolysis and conversion of organic matter in organic-rich shale, as well as the effective recovery of pyrolysis shale oil and gas, play a vital role in alleviating energy pressure. The state of carbon dioxide (CO2) in the pyrolysis environment of shale reservoirs is the supercritical state. Its unique supercritical fluid properties not only effectively heat organic matter, displace pyrolysis products and change shale pore structure, but also achieve carbon storage to a certain extent. Shale samples were made into powder and three sizes of cores, and nitrogen (N2) and supercritical carbon dioxide (ScCO2) pyrolysis experiments were performed at different final pyrolysis temperatures. The properties and mineral characteristics of the pyrolysis products were studied based on gas chromatography analysis, Xray diffraction tests, and mass spectrometry analysis. Besides, the pore structure characteristics at different regions of cores before and after pyrolysis were analyzed using N2 adsorption tests to clarify the impact of fracturing degree on the pyrolysis effect. The results indicate that the optimal pyrolysis temperature of Longkou shale is about 430 °C. Compared with N2, the oil yield of ScCO2 pyrolysis is higher. The pyrolysis oil obtained by ScCO2 extraction has more intermediate fractions and higher relative molecular weight. The ScCO2 can effectively improve the pore diameter of shale and its effect is better than that of N2. The micropores are produced in shale after pyrolysis, and the macropores only are generated in ScCO2 pyrolysis environments with temperatures greater than 430 °C. The pore structure has different development characteristics at different pyrolysis temperatures, which are mainly affected by the pressure holding of volatile matter and products blocking. Compared to the surface of the core, the pore development effect inside the core is better. With the decrease in core size, the pore diameter, specific surface area, and pore volume of cores all increase after pyrolysis. [ABSTRACT FROM AUTHOR]

Vertebral artery dissection is a rare pathology that can cause ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year. [ABSTRACT FROM AUTHOR]

The chiral P,N,N‐ligands represented a new type of tridentate ligand developed in recent years and displayed wide utilities in asymmetric catalysis. In the past decades, numerous chiral P,N,N‐ligands with ferrocene, phenethylamine and spiro backbones were synthesized by addition of an aminopyridine, imidazole or diamines coordinating group. These chiral tridentate P,N,N‐ligands showed excellent performance in the ruthenium, iridium, manganese, or cobalt‐catalyzed asymmetric hydrogenations. A wide range of substrates, including simple ketones, α‐halogenated ketones, α‐hydroxy ketones, α‐ or β‐amino keto‐ ones, α‐, γ‐, or δ‐keto acids, α‐ or β‐keto amides, β‐ or δ‐keto esters, α‐ or β‐enones, olefins, imines, quinolines and indoles, could be hydrogenated to afford the corresponding chiral products with high yields and enantioselectivities. In this review, progress on the asymmetric hydrogenation of C=O, C=N, C=C bonds with chiral tridentate P,N,N‐ligands was summarized. [ABSTRACT FROM AUTHOR]

The study was to establish a method for the simultaneous determination of matrine and oxymatrine in Sanwei Quanshen Koufuye by HPLC. The test compares the detection effects of three amino-chromatographic columns (Agilent ZORBAX NH2, SHISEIDO CAPCELL PAK NH2, Waters SPHERSORB NH2). For separation effect, Agilent ZORBAX NH2 is preferred, but its running time is long. In order to save time and flow equivalent reagents, it was recommended to use SHISEIDO CAPCELL PAK NH2 column first and subselect Waters SPHERSORB NH2 column. After the absolute ethanol extraction, the amino chromatography column (4.6 mm x 250 mm, 5 μm) was used as the separation column, column temperature was 35 °C, and detection wavelength was 220 nm. Diode array detector was used for analysis, and external standard method was used for quantitative determination. The results showed that matrine and oxymatrine showed a good linear relationship ranging between 30 and 300 mg/L (R>0.999 0), and the average sample recovery rate was 97.64% with RSD 1.63%. The system adaptation test and the chromatography column tolerance was good, which fully meet the detection requirements. The study indicates that the method is easy to operate, with good repeatability, stability and accuracy, and can be used for the detection of matrine and oxymatrine contents in Sanwei Quanshen Koufuye. [ABSTRACT FROM AUTHOR]

Tight oil resources are abundant in the world. It is very important to strengthen the research on the development theory and technology of tight oil reservoirs for ensuring national energy security. Natural gas huff-n-puff can effectively improve the oil recovery of tight oil reservoirs. However, the pore-scale oil production characteristics and the mechanisms of natural gas huff-n-puff in matrix-fracture cores are poorly understood. The influence degree of important factors on oil recovery is not clear and the interactions between factors are rarely considered. In this paper, the oil production characteristics and mechanisms of natural gas huff-n-puff in tight cores with different fracture lengths were quantitatively analyzed by combining nuclear magnetic resonance (NMR) with numerical simulation technology. The influencing factors and their interactions were evaluated by the response surface method (RSM). The results show that tight cores mainly consist of medium pores (0.1–1 μm) and small pores (0.01–0.1 μm). The fracture mainly increases the proportion of macro-pores (1–10 μm) and medium pores. In the natural gas huff-n-puff process, crude oil from macro-pores (1–10 μm) and medium pores is mainly developed, and the contribution percentage of crude oil in medium pores to oil recovery is the largest, up to 98.28%. The position of gas–oil contact (GOC) moves deeper as the number of huff-n-puff cycles increases. The contents of CH4 and CO2 in the oil phase remain at a high level within the GOC, while between the GOC and the component sweep front, the contents of CH4 and CO2 in the oil phase decrease with the increase in dimensionless distance. The gas component sweep volume is increasing with the increase in fracture length. Moreover, the injected natural gas mainly extracts C3–C10 components from crude oil. The reduction law of crude oil viscosity is consistent with the migration laws of CH4 components along the path. Compared with soaking time and gas diffusion coefficient, the injection pressure is the most significant factor underlying the recovery of natural gas huff-n-puff in tight cores. Besides the influence of single-factor, the interaction effects of gas injection pressure and diffusion also should be considered to determine the huff-n-puff parameters in the field implementation of natural gas huff-n-puff in tight reservoirs after fracturing. [ABSTRACT FROM AUTHOR]

The purpose of the study was to establish the characteristic atlas of Jingen injection and provide the basis for its quality evaluation. Chlorogenic acid was used as reference, and gradient elution was performed on Waters X Bridge C18 column (diameter 3.5 μm, 4.6 mm x 250 mm) with acetonitrile-0.1% phosphoric acid solution. The detection wavelength was 240 nm, the flow rate was 1.0 mL/min, and the column temperature was 30 °C. The results showed that there were 7 characteristic peaks in the chromatogram, and the retention time was consistent with that of the corresponding reference. The study indicates that the method has high precision, strong specificity and good repeatability, and can control the intrinsic quality of Jinjen injection more effectively. [ABSTRACT FROM AUTHOR]

The optimization of heat conduction is a critical task with widespread applications, and the approaches are typically categorized into two main categories: thermal conductivity distribution optimization (TCDO) and heat source layout optimization (HSLO). While extensive research efforts have been devoted to each of these two categories, standalone TCDO and HSLO limit the design possibilities and may lead to suboptimal solutions. In this work, a collaborative methodology combining TCDO and HSLO is proposed by transforming the collaborative optimization problem into a two-level nested problem. In this approach, TCDO forms the inner subproblem, tackled using the gradient-based method, while HSLO constitutes the outer subproblem addressed through Bayesian optimization (BO). The proposed method is employed to solve two problem cases involving volume-to-point and volume-to-edge boundaries, respectively. The results demonstrate that the present method is capable of achieving collaborative optimization of TCDO and HSLO for both scenarios of continuous and discrete thermal conductivity distributions. Comparing with standalone TCDO and HSLO that reduce the average temperature by ▪ and ▪, respectively, the proposed method achieves a significantly greater reduction of ▪, underscoring its efficacy. We anticipate that the proposed method will serve as a valuable tool for optimizing heat conduction across diverse applications, and its adaptable framework holds promise for addressing broader optimization challenges. • Thermal conductivity and heat source layout are collaboratively optimized. • A nested optimization framework is proposed for the collaborative optimization. • Collaborative optimization outperforms standalone ones by 38.26 K and 82.55 K. • The proposed method is adaptive and efficient for wider range of problems. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized the oncology field. However, a significant number of patients do not respond, at least partly due to the lack of preexisting anti-tumor T-cell immunity. Therefore, it is emergent to add an immune-priming step to improve efficacy. Here, we report a combined approach consisting of intratumoral administration of pro-inflammatory allogeneic dendritic cells (AlloDCs) and systemic treatment with αCTLA-4 that can drastically improve the anti-tumor efficacy compared to αCTLA-4 monotherapy. When evaluated in mice with large established CT-26 tumors, monotherapy with αCTLA-4 neither delayed tumor progression nor improved mice survival. However, combination treatment of AlloDCs and αCTLA-4 drastically improved the effectiveness, with 70% of mice being cured. This effect was T cell-dependent, and all survived mice rejected a subsequent tumor rechallenge. Further investigation revealed an immune-inflamed tumor microenvironment (TME) in the combination treatment group characterized by enhanced infiltration of activated antigen-presenting endogenous DCs and CD8+ T cells with a tissue-resident memory (TRM) phenotype (CD49a+CD103+). This correlated with elevated levels of tumor-specific CD39+CD103+CD8+ T cells in the tumor and "tumormatching" NKG2D+CD39+CX3CR1+CD8+ T cells in peripheral blood. Moreover, splenocytes from mice in the combination treatment group secreted significantly higher IFN-γ upon stimulation with the peptide from the endogenous CT-26 retroviral gp70 (model neoantigen), confirming the induction of a tumorspecific CD8+ T-cell response. Taken together, these data indicate a strong anti-tumor synergy between AlloDCs and αCTLA-4 that warrant further clinical investigation with the corresponding human AlloDC product (ilixadencel) for patients receiving αCTLA-4 therapy. [ABSTRACT FROM AUTHOR]

The asymmetric hydrogenation of β‐ketophosphonates with chiral Ir/P,N,N‐ligands catalyst has been developed. A series of β‐ketophosphonates were hydrogenated, and the corresponding β‐hydroxyphosphonates were obtained in high yields with good or excellent enantioselectivities under mild condition. [ABSTRACT FROM AUTHOR]

Dissociation dynamics of the temporary negative ions of ethanol and acetaldehyde formed by the low-energy electron attachments is investigated by using the anion velocity map imaging technique and ab initio molecular dynamics simulations. The momentum images of the dominant fragments O-/OH- and CH3- are recorded, indicating the low kinetic energies of O-/OH- for ethanol while the low and high kinetic energy distributions of O- ions for acetaldehyde. The CH3- image for acetaldehyde also shows the low kinetic energy. With help of the dynamics simulations, the fragmentation processes are qualitatively clarified. A new cascade dissociation pathway to produce the slow O- ion via the dehydrogenated intermediate, CH3CHO- (acetaldehyde anion), is proposed for the dissociative electron attachment to ethanol. After the electron attachment to acetaldehyde molecule, the slow CH3- is produced quickly in the two-body dissociation with the internal energy redistributions in different aspects before bond cleavages. [ABSTRACT FROM AUTHOR]

The TMC genes encode a set of homologous transmembrane proteins whose functions are not well understood. Biallelic mutations in either TMC6 or TMC8 are detected in more than half of cases of the pre-malignant skin disease epidermodysplasia verruciformis (EV). It is controversial whether EV induced by mutations in TMC6 or TMC8 originates from keratinocyte or lymphocyte defects. Quantification of TMC6 and TMC8 RNA levels in various organs revealed that lymphoid tissues have the highest levels of expression of both genes, and custom antibodies confirmed protein expression in mouse lymphocytes. To study the function of these proteins we generated mice with targeted deletion mutant alleles of Tmc6 or Tmc8. Either TMC6 or TMC8 deficiency induced a reduction in apparent molecular weight and/or amount of the other TMC molecule. Co-immunoprecipitation experiments indicated that TMC6 and TMC8 formed a protein complex in mouse and human T cells. MS and biochemical analysis demonstrated that TMC6 and TMC8 additionally interacted with the CIB1 protein to form TMC6-TMC8-CIB1 trimers. We demonstrated that TMC6 and TMC8 regulated CIB1 levels by protecting CIB1 from ubiquitination and proteasomal degradation. Reciprocally, CIB1 was needed for stabilizing TMC6 and TMC8 levels. These results suggest why inactivating mutations in any of the three human genes leads to similar clinical presentations. We also demonstrated that TMC6 and TMC8 levels are drastically lower and the proteins are less active in regulating CIB1 in keratinocytes than in T cells. Our study suggests that defects in lymphocytes may contribute to the etiology and pathogenesis of EV. [ABSTRACT FROM AUTHOR]

Conventional preparation of porous ceramics often hard to accurately control the porosity of the samples. In this paper, by improving the foaming method, the foaming process is placed in the limited space of the ball mill tank, and YSZ porous ceramics with different porosity are obtained by changing the amount of slurry. Initial results showed that the porosity of the sample varies linearly with the increasing of addition of slurry. From the microscopic morphology, it can be seen that the increase in slurry content will reduce the number of pore with little changed size, which lead to the decrease in porosity. Therefore, with simple calculation YSZ porous ceramics with 85%, 80%, 75%, 70%, and 65% porosity can be obtained using the method of foaming in limited space by ball milling. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro , but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment. • The first report about protein kinase posttranslational function on occurrence PCOS. • CK2α-AR axis promotes AR and ovulation related genes excessive expression. • CK2α promotes KGN cell line proliferation and inhibits apoptosis. • CK2α-AR pathway may serve as a therapeutic target against PCOS. [ABSTRACT FROM AUTHOR]

To facilitate targeting drug delivery and combined therapy, we constructed a novel drug carrier, in which oridonin-liposome containing microbubbles (LUMO) are covalently adhered to folic acid-conjugated multiwalled carbon nanotubes loaded with protohemin (FMTP) to form a novel conjugate (FMTP-LUMO). Oridonin (ORI) is used as a chemotherapeutic drug for chemotherapy (CHT), whereas protohemin (Ph) is applied in the field of sonodynamic therapy (SDT) as a sonosensitizer. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumour effects in HepG-2 cell tumour-bearing mice submitted to chemo-sonodynamic therapy, SDT alone and CHT alone were evaluated upon ultrasound exposure. The results showed that the growth inhibition rates on FMTP-LUMO, FMTP, and LUMO were 95.4 ± 5.9%, 63.9 ± 7.4%, and 42.3 ± 2.9% in vitro, respectively. FMTP-LUMO exhibited strong binding to HepG-2 cells than MTP-LUMO. The chemo-sonodynamic therapy demonstrated a cooperative effect, resulting in significantly higher therapeutic efficacy for liver cancer. After treatment for 10 d, the tumour inhibition ratio for FMTP-LUMO exceeded to 90%, clearly higher than that of FMTP (42.8%) and LUMO (32.5%). Thus, FMTP-LUMO could serve as a highly effective drug carrier for chemo-sonodynamic therapy. [ABSTRACT FROM AUTHOR]

Heat conduction optimization with arbitrary boundary conditions is a challenging problem that lacks a universal optimization criterion. In the present work, the concept of generalized entransy dissipation (GED) is proposed through transforming heat conduction optimization problems with arbitrary boundaries into their homogeneous counterparts. It is demonstrated that minimizing GED leads to optimal thermal performance of heat conduction problems with arbitrary boundary conditions. In addition, GED-based continuous optimization problems are convex, guaranteeing the uniqueness and global optimality of the solution and benefitting numerical calculations. Two typical problems with complex boundary conditions are studied by applying the minimum principle of GED, and the results are compared with other optimization objectives. The numerical results show that GED achieves better thermal performance than entropy generation- (EG) and entransy dissipation- (ED) based optimizations. For the optimization of boundary average temperature under the given input heat flux of ▪, GED achieves the best result, where the optimized average temperature is ▪ and ▪ lower compared with EG and ED optimizations, respectively. In general, GED offers a reasonable and easy to implement optimization principle for heat conduction processes with arbitrary boundaries and may provide new insights for heat conduction optimization. • GED-criterion is proposed for optimizing heat conduction with arbitrary boundaries. • Minimizing GED leads to optimal thermal performance of complex boundary conditions. • Convexity of GED-based continuous optimization guarantees global optimality. • GED outperforms EGMP and EDEP, lowering average temperature by 48.8 and 27.5 K. • GED offers a universal and easy-to-use principle for heat conduction processes. [ABSTRACT FROM AUTHOR]

Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated. [ABSTRACT FROM AUTHOR]

Correlated effects play a significant role in the study of quantum information processing. We investigate the two consecutive uses of the Pauli channels for quantum teleportation without resetting. We find that the existence of correlated action of noise channels is beneficial to improve the fidelity of noisy teleportation in Pauli channels, such as phase-damping, bit-flip and depolarizing channels. Namely, the fidelity increases with the increase of correlated parameter. Our study might provide a new perspective of enhancing the fidelity of quantum teleportation in noisy channels. [ABSTRACT FROM AUTHOR]

Equation of state (EOS) of dense matter has a wide application in geophysics, astrophysics, and physical detonation. However, it is difficult to obtain simple and accurate EOS under ultrahigh-density conditions due to the complex matter structures. Recently, an ideal dense matter EOS based on thermodynamic symmetry has been proposed for ultrahigh-density matter, which is symmetric to ideal gas EOS. Here, owing to experimental limitations, molecular dynamics (MD) is performed to verify the EOS. First, we discuss the feasibility of a thermodynamic integration algorithm for implementing an isentropic process at ultrahigh density. Second, by analogy with heat capacity, we clarify that work capacity reflects the ability of matter to do work. Theoretical analysis shows that internal energy and work capacity of ideal dense matter are independent of temperature. Furthermore, MD simulations demonstrate that the effect of temperature on internal energy and work capacity weakens with increasing density, which conforms to the inference of ideal dense matter EOS. Finally, by simulating isentropic, isothermal, isobaric, and isochoric processes, it is found that the accuracy of ideal dense matter EOS in describing thermodynamic properties is positively related to the density. It is another perspective for the understanding of dense matter and ultrahigh-density EOS. [ABSTRACT FROM AUTHOR]

Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5Mmatured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients. [ABSTRACT FROM AUTHOR]

Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens (TAAs) are frequently used as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidence indicate that ex vivo engineered DCs are poor in migration and in fact do not directly present TAA epitopes to na€ıve T cells in vivo. Instead, it is proposed that bystander host DCs take up material from vaccine-DCs, migrate and subsequently initiate antitumor T-cell responses. We used mouse models to examine the possibility of using pro-inflammatory allogeneic DCs (alloDCs) to activate host DCs and enable them to promote antigen-specific T-cell immunity. We found that alloDCs were able to initiate host DC activation and migration to draining lymph node leading to T-cell activation. The proinflammatory milieu created by alloDCs also led to recruitment of NK cells and neutrophils at the site of injection. Vaccination with alloDCs combined with Ad5M(gp100), an infection-enhanced adenovirus encoding the human melanoma-associated antigen gp100 resulted in generation of CD8C T cells with a T-cell receptor (TCR) specific for the gp10025-33 epitope (gp100-TCRC). Ad5M(gp100)-alloDC vaccination in combination with transfer of gp100-specific pmel-1 T cells resulted in prolonged survival of B16-F10 melanoma-bearing mice and altered the composition of the tumor microenvironment (TME). We hereby propose that alloDCs together with TAA- or neoepitope-encoding Ad5M can become an "off-the-shelf" cancer vaccine, which can reverse the TME-induced immunosuppression and induce host cellular anti-tumor immune responses in patients without the need of a time-consuming preparation step of autologous DCs. [ABSTRACT FROM AUTHOR]

The Ir-catalyzed asymmetric hydrogenation of simple aromatic ketones with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of ketones were hydrogenated to afford the corresponding chiral alcohols in good to excellent enantioselectivities (up to 98% ee). [ABSTRACT FROM AUTHOR]

A novel space vector modulation strategy in the non-orthogonal three-dimensional coordinate system for multi-level three-phase four-wire inverters is proposed in this paper. This new non-orthogonal three-dimensional space vector modulation converts original trigonometric functions in the orthogonal three-dimensional space coordinate into simple algebraic operations, which greatly reduces the algorithm complexity of three-dimensional space vector modulation and preserves the independent control of the zero-sequence component. Experimental results have verified the correctness and effectiveness of the proposed three-dimensional space vector modulation in the new non-orthogonal three-dimensional coordinate system. [ABSTRACT FROM AUTHOR]

We report on a p-i-n photodetector based on type II InGaAs/GaAsSb SLs with a cutoff wavelength of 2.5 μm at room temperature. High quality materials were grown on an n-type (100) InP substrate by molecular beam epitaxy. Photoluminescence spectroscopy peak of the SLs around 2.5 μm and atomic steps in the atomic force microscope image were clearly observed. A device with the 100% cutoff wavelength of 2.5 μm at 293 K was fabricated. Temperature-dependent current-voltage measurements show that the diffusion current and generation- recombination current dominate at temperatures higher than 200 K while the generation-recombination current and trap-assisted tunneling current dominate at temperatures below 200 K. The optical response measurement quantum efficiency increases with reverse bias, and a diffusion length of 0.3 μm was extracted. The cause of the small diffusion length and possible approaches to improve it were briefly discussed. [ABSTRACT FROM AUTHOR]

A copper-catalyzed domino cyclization of propargylic alcohols with tosyl isocyanate for the synthesis of oxazolidinones has been developed. Various propargylic alcohols with an aryl or alkyl substituents worked smoothly to afford the corresponding oxazolidinones in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

Chiral phosphine-phosphoramidite ligands, featuring ready availability, easy modification, and stability towards air and moisture, have recently emerged as a new kind of robust ligands for asymmetric catalysis. They have been found to display wide utilities in various catalytic asymmetric reactions, giving excellent enantioselectivities in the Rh-, Ru-, and Ir-catalyzed asymmetric hydrogenation of C˭C, C˭O, and C˭N double bonds; Rh-catalyzed asymmetric hydroformylation; Pd-catalyzed asymmetric hydrophosphorylation; Pd-catalyzed asymmetric allylic alkylation; Ag-catalyzed asymmetric [3 + 2] cycloaddition; and Cu-catalyzed conjugate addition and reduction. In this review, the progress on the development of chiral phosphine-phosphoramidite ligands in asymmetric catalysis has been summarized. [ABSTRACT FROM PUBLISHER]

Preclinical Research Sonodynamic therapy (SDT) is a cutting edge approach to treating cancer that involves necrosis and/or apoptosis. Multiwalled carbon nanotubes functionalized with carboxylic groups (MWCNTs ‐ COOH) due their physicochemical structure represent a novel drug delivery system in the field of nanomedicine. The purpose of the research reported in this paper was to increase the antitumor potency and reduce the potential side effects of protohemin (Ph), a sonosensitizer for SDT, which was noncovalently encapsulated into MWCNTs ‐ COOH (MWCNTs ‐ Ph). The Ph loading efficiency in MWCNTs ‐ COOH carrier was determined as approximately 68.8% (w/w). The growth inhibition rate of MWCNTs ‐ Ph (Ph: 180 μg/mL) was approximately 95 ± 8.5%, whereas Ph ‐ F (Ph: 180 μg/mL) inhibited 58 ± 4.5% of tumor cell. Ph (Ph: 180 μg/mL) alone had no antitumor effect in HepG ‐ 2 cells using ultrasound treatment at 1.0 MHz and 0.5 W/cm2 for 100 s. Assessment of the antitumor effects of MWCNTs ‐ Ph and Ph ‐ F at day 11 after SDT showed that he tumor inhibition ratio for MWCNTs ‐ Ph (6.18 × 10−2 g·kg−1·d−1) was 82.8%, twice that of Ph ‐ F (6.18 × 10−2 g·kg−1·d−1) ay 41.8%. In conclusion, MWCNTs ‐ Ph had increased antitumor efficiency and also decreased potential side effects. Drug Dev Res 77 : 152 – 158, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel Virtual Space Vector (VSV) modulation strategy for complete control of potential neutral point (NP) issues is proposed in this paper. The neutral point potential balancing problems of multi-level converters, which include elimination of low frequency oscillations and self-balancing for NP dc unbalance, are investigated first. Then a set of improved virtual space vectors with dynamic adjustment factors are introduced and a multi-objective optimization algorithm which aims to optimize these adjustment factors is presented in this paper. The improved virtual space vectors and the multi-objective optimization algorithm constitute the novel Virtual Space Vector modulation. The proposed novel Virtual Space Vector modulation can simultaneously recover NP dc unbalance and eliminate low frequency oscillations of the neutral point. Experiment results show that the proposed strategy has excellent performance, and that both of the neutral point potential issues can be solved. [ABSTRACT FROM AUTHOR]

Background Left-sided colonic pathologies requiring emergency resection are commonly encountered on an acute surgical unit. Subspecialist colorectal ( CR) management of these patients may result in decreased morbidity, mortality and stoma rates. This study is the first of its kind comparing outcomes between CR surgeons and general surgeons on an acute surgical unit. Methods This is a retrospective review of 196 consecutive patients who underwent emergency left colonic resection on an acute surgical unit between January 2009 and July 2014. Patients were divided into two groups dependent on whether their surgery was managed by a CR specialist or general surgeon. Primary outcome measures were 30-day mortality, rate of primary anastomosis and overall stoma rate. Results Patients in the two groups were comparable for age, sex, American Society for Anesthesiologists score as well as CR POSSUM scores. Rates of primary anastomosis were significantly higher in the CR group compared with the acute surgical unit group (85.5 versus 28.7%, P ≤ 0.001). Overall stoma rates were significantly lower in the CR group (40.4 versus 88.8%, P = 0.0001). Thirty-day mortality was similar in both groups. Other secondary markers of morbidity including length of stay, return to theatre, anastomotic leak rate, wound problems and systemic complications had no significant difference between the two groups. Conclusion Subspecialist CR management of patients undergoing emergency left-sided colonic resection on an acute surgical unit is associated with a similar level of morbidity and mortality while safely achieving significantly higher rates of primary anastomosis and lower stoma rates. [ABSTRACT FROM AUTHOR]

Rh-catalyzed asymmetric hydrogenation of challenging α-keto phosphonates has been developed. With a new chiral phosphine–phosphoramidite ligand, a wide range of α-keto phosphonates were hydrogenated to afford the corresponding ( R )-α-hydroxy phosphonates with moderate to good enantioselectivities (up to 87% ee). [ABSTRACT FROM AUTHOR]

Distance measuring equipment (DME) provides pilots with distance information between the aircraft and the ground station, and is used in all phases of flight. DME/DME RNAV is authorized for navigation on China Area Navigation (RNAV) routes, where DME ranging from at least two DME facilities are used to determine the aircraft's horizontal position. In order to precisely determine whether the DME/DME RNAV operation accuracy meets China Area Navigation authorized specification, the weighted least-squares algorithm is given out. Then, the DME/DME horizontal accuracy model and RNAV accuracy model were built. Based on the horizontal accuracy model, the method is applied to analyze the horizontal accuracy of DME/DME, where only two DME rangings are used. And, based on the RNAV accuracy model, the position accuracy of three common cases of the DME/DME RNAV operation is computed and simulated. The simulated results show that the DME/DME RNAV operation accuracy depends on the accuracy of each DME ranging signals as well as the inclusion angle between the two DMEs used in determining the position. So, these results can be served for DME/DME RNAV flight management system in DME stations selection and station switch. [ABSTRACT FROM AUTHOR]

The article offers information on a research conducted by the authors on the effect of the effect of the bacteria Helicobacter pylori neutrophil-activating protein (HP-NAP) on maturation of dendritic cells (DC) and induction of adaptive immune response. Topics discussed include promoting DC maturation and migration by vector-encoded HP-NAP, ability of vector-encoded HP-NAP DC to induce antigen (Ag) specific T cell expansion, and activation of DC for Ag-specific response in therapeutic purposes.

Epithelial cell adhesion molecule (EpCAM) (CD326) is a surface glycoprotein expressed by invasive carcinomas and some epithelia. Herein, we report that EpCAM regulates the composition and function of tight junctions (TJ). EpCAM accumulated on the lateral interfaces of human colon carcinoma and normal intestinal epithelial cells but did not co-localize with TJ. Knockdown of EpCAM in T84 and Caco-2 cells using shRNAs led to changes in morphology and adhesiveness. TJ formed readily after EpCAM knockdown; the acquisition of trans-epithelial electroresistance was enhanced, and TJ showed increased resistance to disruption by calcium chelation. Preparative immunoprecipitation demonstrated that EpCAM bound tightly to claudin-7. Co-immunoprecipitation documented associations of EpCAM with claudin-7 and claudin-1 but not claudin-2 or claudin-4. Claudin-1 associated with claudin-7 in co-transfection experiments, and claudin-7 was required for association of claudin-1 with EpCAM. EpCAM knockdown resulted in decreases in claudin-7 and claudin-1 proteins that were reversed with lysosome inhibitors. Immunofluorescence microscopy revealed that claudin-7 and claudin-1 continually trafficked into lysosomes. Although EpCAM knockdown decreased claudin-1 and claudin-7 protein levels overall, accumulations of claudin-1 and claudin-7 in TJ increased. Physical interactions between EpCAM and claudins were required for claudin stabilization. These findings suggest that EpCAM modulates adhesion and TJ function by regulating intracellular localization and degradation of selected claudins. [ABSTRACT FROM AUTHOR]

Preclinical Research The expression of the folate receptor (FR) is amplified in many cancer types. Oridonin (ORI, C20H28O6) is an isolate from Rabdosia rubescens (Hemsl.) Hara that has been used in the treatment of esophageal and hepatic carcinoma for decades. In order to enhance the antitumor potency of ORI, folate ‐ polyethylene glycol2000 ‐ distearoylphosphatidyleth ‐ anolamine (folate ‐ PEG2000 ‐ DSPE) was synthesized to facilitate preparation of FR ‐ targeted liposomal ORI (F ‐ L ‐ ORI). F ‐ L ‐ ORI and PEG2000 ‐ DSPE ‐ L ‐ ORI were then prepared. In vitro release properties, cellular uptake, and cytotoxicity in HepG ‐ 2 cells, as well as in vivo potency of the liposomes in murine HepG ‐ 2 tumor ‐ bearing mice were evaluated. An in vitro cytotoxicity assay on F ‐ L ‐ ORI gave an IC50 value of 0.718 ± 0.023 μmol/ml and L ‐ ORI had an IC50 value of 2.25 ± 0.12 μmol/ml. These liposomes were able to control the release of ORI. In vitro cells binding of F ‐ L ‐ ORI exhibited higher binding to HepG ‐ 2 cells as compared with L ‐ ORI. The antitumor effect studies assessed in vivo showed that F ‐ L ‐ ORI improved the antitumor activity of ORI as compared with L ‐ ORI and free drug. The tumor inhibition ratio for F ‐ L ‐ ORI (1.5 × 10−2 g/kg/d) was 85.6%, higher than that of L ‐ ORI group (1.5 × 10−2 g/kg/d) and free ORI (1.5 × 10−2 g/kg/d) that were 66.8% and 40.8%, respectively. [ABSTRACT FROM AUTHOR]

Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus-receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research. [ABSTRACT FROM AUTHOR]

A mild and general iridium-catalyzed, highly enantioselective hydrogenation of sterically hindered N-arylimines with a new H8-BINOL-derived phosphine–phosphoramidite ligand has been developed. The present catalytic system features high turnover numbers (up to 100000) and good to perfect enantioselectivities (up to 99% ee) for the hydrogenation of a variety of sterically hindered N-arylimines. [ABSTRACT FROM AUTHOR]

Abstract: The asymmetric conjugate reduction of 3-aryl-4-phosphonobutenoates has been demonstrated which provides an enantioselective synthesis of optically active 3-aryl-4-phosphonobutyric acid esters. A wide range of 3-aryl-4-phosphonobutenoate derivates are reduced with high enantioselectivities (up to 94% ee) using an (S)-Segphos/Cu(OAc)2·H2O catalyst system (1 or 5mol%) in the presence of PMHS and t-BuOH. The reduction is influenced by the steric and electronic effects of the substrates. [Copyright &y& Elsevier]

Abstract: Unsymmetrical hybrid chiral ferrocenyl phosphine-phosphoramidite ligands have been applied for the first time in the Cu-catalyzed asymmetric 1,4-reduction of β-aryl substituted α,β-unsaturated esters. The results show that the ligand bearing (Sc )-central, (Rp )-planar, and (Ra )-axial chiralities gave the best performance. The present catalytic system proved to be highly substrate-dependent, catalyzing the conjugate reduction of α,β-unsaturated esters in moderate to excellent enantioselectivities. [Copyright &y& Elsevier]

The mechanism by which the Carma1-Bcl10-MALT1 (CBM) complex couples T cell antigen receptor (TCR) signaling to IκB kinase (IKK) and NF-κB activation is not known. Here, we show that Bcl10 undergoes K63-linked polyubiquitination in response to T cell activation and subsequently binds NEMO, the regulatory subunit of IKK. This interaction requires the ubiquitin-binding activity of NEMO. The sites of Bcl10 ubiquitination were mapped to K31 and K63. Mutation of these residues did not affect TCR signaling-induced CBM complex assembly but prevented Bcl10 ubiquitination, NEMO binding, and NF-κB activation. Therefore, the regulated ubiquitination of Bcl10 and its recognition by NEMO are a critical link between the CBM complex, IKK recruitment, and NF-κB activation. [ABSTRACT FROM AUTHOR]

Abstract: Racemic 12-hydroxyl-1,15-pentadecanlactam 2 was resolved using glucose as a chiral auxiliary for the first time. Both the (R)- and (S)-isomers were obtained in high enantiomeric excesses (>99% by HPLC). The absolute configuration of (+)-2b and (−)-2a was determined by Horeau’s method and a modified Mosher’s method. [Copyright &y& Elsevier]

Summary: NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) that activates NF-κB, is essential for NF-κB activation . NEMO was recently found to contain a region that preferentially binds Lys (K)63-linked but not K48-linked polyubiquitin (polyUb) chains, and the ability of NEMO to bind to K63-linked polyUb RIP (receptor-interacting protein) is necessary for efficient tumor necrosis factor α (TNFα)-induced NF-κB activation . Optineurin is a homolog of NEMO, and mutations in the optineurin gene are found in a subset of patients with glaucoma , a neurodegenerative disease involving the loss of retinal ganglion cells . Although optineurin shares considerable homology with NEMO, in resting cells, it is not present in the high-molecular-weight complex containing IKKα and IKKβ, and optineurin cannot substitute for NEMO in lipopolysaccharide (LPS)-induced NF-κB activation . On the other hand, the overexpression of optineurin blocks the protective effect of E3-14.7K on cell death caused by the overexpression of TNFα receptor 1 (TNFR1) . Here we show that optineurin has a K63-linked polyUb-binding region similar to that of NEMO, and like NEMO, it bound K63- but not K48-linked polyUb. Optineurin competitively antagonized NEMO''s binding to polyUb RIP, and its overexpression inhibited TNFα-induced NF-κB activation. This competition occurs at physiologic protein levels because microRNA silencing of optineurin resulted in markedly enhanced TNFα-induced NF-κB activity. These results reveal a physiologic role for optineurin in dampening TNFα signaling, and this role might provide an explanation for its association with glaucoma. [Copyright &y& Elsevier]

The transcription factor NF-κB is sequestered in the cytoplasm in a complex with IκB. Almost all NF-κB activation pathways converge on IκB kinase (IKK), which phosphorylates IκB resulting in Lys 48-linked polyubiquitination of IκB and its degradation. This allows migration of NF-κB to the nucleus where it regulates gene expression. IKK has two catalytic subunits, IKKα and IKKβ, and a regulatory subunit, IKKγ or NEMO. NEMO is essential for NF-κB activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti and hypohidrotic ectodermal dysplasia and immunodeficiency (HED–ID). The recruitment of IKK to occupied cytokine receptors, and its subsequent activation, are dependent on the attachment of Lys 63-linked polyubiquitin chains to signalling intermediates such as receptor-interacting protein (RIP). Here, we show that NEMO binds to Lys 63- but not Lys 48-linked polyubiquitin, and that single point mutations in NEMO that prevent binding to Lys 63-linked polyubiquitin also abrogates the binding of NEMO to RIP in tumour necrosis factor (TNF)-α-stimulated cells, the recruitment of IKK to TNF receptor (TNF-R) 1, and the activation of IKK and NF-κB. RIP is also destabilized in the absence of NEMO binding and undergoes proteasomal degradation in TNF-α-treated cells. These results provide a mechanism for NEMO's critical role in IKK activation, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-κB activation. [ABSTRACT FROM AUTHOR]

Abstract: Macroreticular p-(ω-sulfonic-perfluoroalkylated)polystyrene (FPS) resins have been synthesized at mild conditions by following suspension polymerization of styrene and divinylbenzene, perfluoroalkylation by ω-fluorosulfonylperfluorodiacyl peroxides (SFAP), alkali hydrolysis and acidification. The macroreticular FPS resins with terminal perfluorosulfonic acid group were characterized by FTIR, SEM, TGA, acidimetry and nitrogen sorption technique. The resins have higher exchange capacity and surface area than perfluorinated resin Nafion NR50, and better thermostability than nonfluorinated sulfonic resin Amberlyst 15. The influences of the type and the amount of porogen, the crosslinker degree, the chain length of perfluoroalkylating reagent as well as the extent of perfluoroalkylation on the resin''s properties were investigated. The FPS resins exhibited higher activity and selectivity than several commercial cation-exchange resins in the synthesis of ionone and diindolylmethanes (DIMs). [Copyright &y& Elsevier]

Signaling through tumor necrosis factor receptor 2 (TNF-R2) results in ubiquitination of TRAF2 by the E3 c-IAP1. In this report, we confirm that TRAF2 translocates to a Triton X-100 (TX)-insoluble compartment upon TNF-R2 engagement. Moreover, TRAF2 ubiquitination occurs in this compartment, from which TRAF2 is degraded in a proteasome-dependant manner. Confocal microscopy demonstrated that the TX-insoluble compartment is perinuclear and co-localizes with endoplasmic reticulum (ER) markers. The ER transmembrane Ubc6 bound to c-IAP1 and served as a cognate E2 for c-IAP1's E3 activity in vitro. Furthermore, Ubc6 co-localized with translocated TRAF2/c-IAP1 in the ER-associated compartment in vivo, and a catalytically inactive Ubc6 mutant inhibited TNF-a-induced, TNF-R2-dependent TRAF2 degradation. These results indicate that upon TNF-R2 signaling, translocation of TRAF2 and c-IAP1 to an ER-associated, Ubc6-containing perinuclear compartment is required for the ubiquitination of TRAF2 by c-IAP1. Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. [ABSTRACT FROM AUTHOR]

The condensation reactions of indole with some carbonyl compounds were found to be catalyzed effectively by ion exchange resins under mild conditions. [ABSTRACT FROM AUTHOR]

Background Low incomes may not provide the minimum requirements for healthy living. We evaluated experiences of food insecurity in relation to income in inner London. [ABSTRACT FROM PUBLISHER]

Stable s-butyl trifluoroacetyl nitroxide (3) has been generated in electron-transfer reaction of O-benzoyl-N-s-butylhydroxylamine (1) and trifluoroacetyl peroxide (2) in F113 (CFCl[sub 2]CF[sub 2]Cl) solution at room temperature. ESR measurement of a[sub N] and a[sub H][sup β] values for 3 in 21 solvents has been carried out at 24~ 25°C. The a[sub N] values for 3 in 12 aprotic solvents show a linear correlation with the cybotactic solvent parameters E[sub T] and Z, i.e. a[sub N] = 1.35×10-[sup 2] E[sub T]+6.84, a[sub N] = 0.78×10-[sup 2]Z+6.88. The physical significance for the slopes, slope × E[sub T] or slope × Z, the extrapolated intercepts on the a[sub N] axis are linked to the sensitivity of the nitroxide toward the solvation, the magnitude of the overall solvaton effect on the a[sub N] values, and the intrinsic a[sub N] value of 3 in the ideal gaseous state, respectively. The plots of a[sub N] versus noncybotactic solvent constants, such as dipolar moment (μ) and dielectric constant (ε), all show random cases. [ABSTRACT FROM AUTHOR]