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The parent HZSM-5 was modified with oxide M (M = Fe, Cu, La, P) via the incipient impregnation method by using ferric nitrate, copper nitrate, lanthanum nitrate and diammonium hydrogen phosphate as precursors to prepare a series of oxide M modified HZSM-5 (M/HZSM-5). And the M/HZSM-5 used as solid acid was physically mixed with commercial Cu/ZnO/Al2O3 to obtain bifunctional catalysts for steam reforming of dimethyl ether (SRD) reaction. The samples were systematically characterized by XRD, FTIR, N2 adsorption–desorption, and NH3-TPD techniques. The results showed that HZSM-5 structure remained basically unchanged after it was modified by oxide M; however, its specific surface area, pore volume, total acid amount, especially strong acid amount was decreased, and then affecting the DME conversion, H2 yield and carbon-containing product selectivity of the corresponding bifunctional catalyst. Among them, the bifunctional catalyst composed of Cu/ZnO/Al2O3 and La/HZSM-5 with the larger specific surface area and lower strong acid sites showed best SRD performance, and the dimethyl ether conversion and H2 yield reached 90.4% and 73.9% at TOS of 10 h under the conditions of reaction temperature 300 °C, pressure 0.1 MPa, space velocity 5000 mL/(g h), respectively. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to systematically review the literature on the clinical outcomes following different surgical techniques in patients with refractory idiopathic intracranial hypertension (IIH). Background: IIH is a condition characterised by increased cranial pressure (ICP) in the absence of an intracranial lesion that does not adequately respond to different medical and surgical therapies. Cranial decompression or expansion surgeries are a last resort therapy for patients with refractory IIH. Methods: A systematic literature search of the databases of PubMed, Embase and Medline from inception to 2019 was performed. Searches were limited to the English language and to clinical studies. Studies were included if clinical outcomes following different cranial decompression or expansion techniques were reported. We also add one case of our own experience with performing a bilateral frontoparietal expansion craniotomy and subtemporal craniectomy. Results: Five manuscripts, describing 38 procedures, met the inclusion criteria. Thirty-one patients were female (82%). The mean age was 26.2 years. The techniques studied included subtemporal craniectomy (27/38, 71%), internal cranial expansion (10/38, 26%), and cranial morcellation decompression (1/38, 3%). Thirty-five patients presented with headaches of which 17 noted postoperative improvement or resolution (49%). Visual deficits were documented in 30 patients and 25 reported postoperative improvement (83%). Papilledema disappeared in 23 of 32 patients with this sign at presentation (72%). In our patient, symptoms completely resolved postoperatively and a 6% increase in intracranial volume was measured. Conclusions: Cranial vault decompression or expansion surgeries may be an effective last resort therapy for patients with refractory IIH. These surgeries expand the intracranial volume, and thus may normalise ICP, leading to clinical improvement. [ABSTRACT FROM AUTHOR]

This paper presented a new control strategy for active suspension of nonlinear quarter-vehicle model. An active suspension controller designed for using sliding mode control with noise filtering. The Kalman filter (KF) predicted the state response of the nonlinear one-quarter automobile model, and the estimated values used for the design of the active control force. Finally, the shock absorption performance compared with the LQR controller and the passive suspension. The simulation results showed that the control method significantly improve the ride performance and safety of the vehicle. [ABSTRACT FROM AUTHOR]

The amyloid precursor-like protein 2 (APLP2) molecule is a type I transmembrane protein that is crucial for survival, cell-cell adhesion, neuronal development, myelination, cancer metastasis, modulation of metal, and glucose and insulin homeostasis. Moreover, the importance of the amyloid precursor protein (APP) family in biology and disease is very well known because of its central role in Alzheimer disease. In this study, we determined the crystal structure of the independently folded E2 domain of APLP2 and compared that with its paralogues APP and APLP2, demonstrating high overall structural similarities. The crystal structure of APLP2 E2 was solved as an antiparallel dimer, and analysis of the protein interfaces revealed a distinct mode of dimerization that differs from the previously reported dimerization of either APP or APLP1. Analysis of the APLP2 E2 metal binding sites suggested it binds zinc and copper in a similar manner to APP and APLP1. The structure of this key protein might suggest a relationship between the distinct mode of dimerization and its biologic functions. [ABSTRACT FROM AUTHOR]

To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly β-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other KATP channel openers. [ABSTRACT FROM AUTHOR]

Lysobacter is a Gram-negative genus comprising a group of environmental bacteria with abilities to produce abundant novel antibiotics, as well as adopting a unique type IV pilus (T4P)-mediated twitching motility (TM) that remains poorly understood. Here, we employ L. enzymogenes OH11 exhibiting significant antifungal activity as a working model to address this issue. Via mutating the 28 potential sigma factors in strain OH11, we have identified one protein RpoNOH11 (sigma 54) that is indispensable for T4P formation and TM. We further showed that RpoNOH11 not only regulates the transcription of pilA, but also another crucial gene chpA that encodes a hybrid two-component transduction system. The L. enzymogenes RpoNOH11 was found to directly bind to the promoter of chpA to control its transcription, which is found to be essential for the T4Pmediated TM. To our knowledge, such a transcriptional regulation performed by RpoN in control of bacterial TM has never been reported. Finally, we showed that L. enzymogenes OH11 could also produce biofilm that is likely employed by this strain to infect fungal pathogens. Mutation of rpoNOH11, pilA and chpA all led to a significant decrease in biofilm formation, suggesting that the dual transcriptional regulation of pilA and chpA by RpoNOH11 plays a key role for RpoNOH11 to modulate the biofilm formation in L. enzymogenes. Overall, this study identified chpA as a new target of RpoN for controlling the T4P-mediated twitching motility and biofilm formation in L. enzymogenes OH11. [ABSTRACT FROM AUTHOR]

Lysobacter enzymogenes is a Gram-negative, environmentally ubiquitous bacterium that produces a secondary metabolite, called heat-stable antifungal factor (HSAF), as an antifungal factor against plant and animal fungal pathogens. 4-Hydroxybenzoic acid (4-HBA) is a newly identified diffusible factor that regulates HSAF synthesis via L. enzymogenes LysR (LysRLe), an LysR-type transcription factor (TF). Here, to identify additional TFs within the 4-HBA regulatory pathway that control HSAF production, we reanalyzed the LenB2-based transcriptomic data, in which LenB2 is the enzyme responsible for 4-HBA production. This survey led to identification of three TFs (Le4806, Le4969, and Le3904). Of them, LarR (Le4806), a member of the MarR family proteins, was identified as a new TF that participated in the 4-HBA-dependent regulation of HSAF production. Our data show the following: (i) that LarR is a downstream component of the 4-HBA regulatory pathway controlling the HSAF level, while LysRLe is the receptor of 4-HBA; (ii) that 4-HBA and LysRLe have opposite regulatory effects on larR transcription whereby larR transcript is negatively modulated by 4-HBA while LysRLe, in contrast, exerts positive transcriptional regulation by directly binding to the larR promoter without being affected by 4-HBA in vitro; (iii) that LarR, similar to LysRLe, can bind to the promoter of the HSAF biosynthetic gene operon, leading to positive regulation of HSAF production; and (iv) that LarR and LysRLe cannot interact and instead control HSAF biosynthesis independently. These results outline a previously uncharacterized mechanism by which biosynthesis of the antibiotic HSAF in L. enzymogenes is modulated by the interplay of 4-HBA, a diffusible molecule, and two different TFs. [ABSTRACT FROM AUTHOR]

Multiple description (MD) coding is a promising alternative for the robust transmission of information over error-prone channels. In 3D image technology, the depth map represents the distance between the camera and objects in the scene. Using the depth map combined with the existing multiview image, it can be efficient to synthesize images of any virtual viewpoint position, which can display more realistic 3D scenes. Differently from the conventional 2D texture image, the depth map contains a lot of spatial redundancy information, which is not necessary for view synthesis, but may result in the waste of compressed bits, especially when using MD coding for robust transmission. In this paper, we focus on the redundancy removal of MD coding based on the DCT (discrete cosine transform) domain. In view of the characteristics of DCT coefficients, at the encoder, a Lagrange optimization approach is designed to determine the amounts of high frequency coefficients in the DCT domain to be removed. It is noted considering the low computing complexity that the entropy is adopted to estimate the bit rate in the optimization. Furthermore, at the decoder, adaptive zero-padding is applied to reconstruct the depth map when some information is lost. The experimental results have shown that compared to the corresponding scheme, the proposed method demonstrates better rate central and side distortion performance. [ABSTRACT FROM AUTHOR]

Abstract: Nickel-catalyzed N-heteroaromatics, such as pyridine, pyrazine or pyrimidine-directed cross-coupling of fluorinated arenes with organozinc reagents in the presence of sodium and PCy3 was reported. [Copyright &y& Elsevier]

Simple Summary: CD20-targeting CAR T cells have shown remarkable clinical outcomes in patients with B-cell malignancies. However, the manufacturing processes usually involved in autologous cell collection and gene editing limit their usage and development across the board. Here, we developed an allogenic cell product ACE1831, Vγ9Vδ2 T (γδ2 T) cells equipped with anti-CD20 antibody, using antibody–cell conjugation (ACC) technology. ACE1831 elicits a specific and potent anti-tumor activity against CD20-expressing cancer cells in vitro and in vivo with no abnormal clinical observation. We further found that the ACC-linked antibody/receptor complex stimulated T cell activation upon recognizing the antigen on cancer cells. To summarize, our data show the promise of a novel combination of an ACC platform with γδ2 T cells in allogenic immunotherapy against relapsed/refractory B-cell lymphoma. Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody–cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma. [ABSTRACT FROM AUTHOR]

M1 macrophages are involved in inflammation by producing proinflammatory cytokines, whereas M2 macrophages are associated with wound healing and tissue regeneration by producing anti-inflammatory cytokines. MicroRNAs are involved in macrophage polarization. To evaluate whether miR-15a/16 is involved in macrophage polarization under tumour or inflammation microenvironments, we observed the growth of transplanted hepatic cancer (H22) cells or severity of dextran sulphate sodium (DSS)-induced colitis in 8-week-old miR-15a/16 knockout (KO) mice. Compared with littermate controls, the miR-15a/16-/- mice exhibited retarded tumour growth and increased sensibility to DSS-induced colitis. Meanwhile, the M1 cell frequencies were higher in tumour tissues and inflamed colons of KO mice than of littermate controls. Macrophages with miR-15a/16 deletion revealed an enhanced NF-κB transcription under the physiological state and lipopolysaccharide (LPS) or high mobility group box 1 (HMGB1) stimulation. STAT3 expression was also significantly increased in miR-15a/16-/- macrophages under LPS or HMGB1 stimulation. The polarization of M1 macrophages can be associated with the coactivation of NF-κB and STAT3. Results indicated that miR-15a/16 deficiency in the macrophages directs M1 polarization for tumour suppression and proinflammation. Thus, miR-15a/16 deletion in macrophages holds a distinct biological significance from that of the microRNA deficiency in tumour cells. [ABSTRACT FROM AUTHOR]

A novel Ni-catalyzed cross-coupling of fluoroarenes is developed using alkyl zinc reagents in the presence of sodium. [ABSTRACT FROM AUTHOR]

Objective: Hepatocellular carcinoma (HCC), the main type of liver cancer, has a high morbidity and mortality, and a poor prognosis. RNA helicase DDX5, which acts as a transcriptional co-regulator, is overexpressed in most malignant tumors and promotes cancer cell growth. Heat shock protein 90 (HSP90) is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival. Methods: DDX5 mRNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot, respectively. The interaction of DDX5-HSP90 was determined by molecular docking, immunoprecipitation, and laser scanning confocal microscopy. The autophagy signal was detected by Western blot. The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines. Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor. Results: HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway. The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating the β-catenin signaling pathway. The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model. High levels of HSP90 and DDX5 protein were associated with poor prognoses. Conclusions: HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation. DDX5 and HSP90 are therefore potential therapeutic targets for HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor T cell therapy has shown its potency against hematologic malignancies in autologous settings but also limited success against solid tumors with severe adverse events, including fatal cases of cytokine releasing syndrome. The aim of this research is to develop a novel off-the-shelf natural killer cell therapy against HER2-expressing cancers using Antibody-Cell Conjugation (ACC) technology and the endogenous CD16-expressing oNK cell line. ACE1702, trastuzumab-armed oNK cells with γ irradiation and cryopreservation, present superior in vitro and in vivo potency against HER2-expressing cancer cells and shows no tumorigenic potential, indicating the clinical application fighting HER2-expressing solid tumors. These findings suggest that ACC technology can be applied to allogeneic immune cells to provide off-the-shelf therapies for cancer patients. Natural killer (NK) cells harbor efficient cytotoxicity against tumor cells without causing life-threatening cytokine release syndrome (CRS) or graft-versus-host disease (GvHD). When compared to chimeric antigen receptor (CAR) technology, Antibody-Cell Conjugation (ACC) technology has been developed to provide an efficient platform to arm immune cells with cancer-targeting antibodies to recognize and attack cancer cells. Recently, we established an endogenous CD16-expressing oNK cell line (oNK) with a favorable expression pattern of NK activation/inhibitory receptors. In this study, we applied ACC platform to conjugate oNK with trastuzumab and an anti-human epidermal growth factor receptor 2 (HER2) antibody. Trastuzumab-conjugated oNK, ACE-oNK-HER2, executed in vitro and in vivo cytotoxicity against HER2-expressing cancer cells and secretion of IFNγ. The irradiated and cryopreserved ACE-oNK-HER2, designated as ACE1702, retained superior HER2-specific in vitro and in vivo potency with no tumorigenic potential. In conclusion, this study provides the evidence to support the potential clinical application of ACE1702 as a novel off-the-shelf NK cell therapy against HER2-expressing solid tumors. [ABSTRACT FROM AUTHOR]

The study of the flow characteristics of the solid-fluid two phase flow in the cutter suction dredger is very important for exploring the slurry formation mechanism and optimizing the operational parameters. In this study, standard k-e model and Multiple Reference Frame are applied to numerically simulate flow field in and around the cutting system, then with the steady convergent result of the simulation as the initial condition, Discrete Phase Mode is used to solve the particle motion equation by fully coupling the continuous phase and the particles. The influence of suction flow velocity and cutter's rotating speed on particles suction are analyzed, and effectively suctioned particles numbers are also quantitatively studied. The simulation result shows that the DPM model is able to simulate the movement of particles in and around the cutter suction dredger's cutting system, in the fluid flow filed velocity vector and pressure distribution on different planes show different characteristics, and under higher suction velocity and lower cutter rotating speed more particles are suctioned into the suction inlet. The results can help better understand flow characteristics of solidfluid 2-phase-flow of cutter suction dredger's cutting system, and provide theoretical support for relative system design and operational parameters optimization. [ABSTRACT FROM AUTHOR]

A method for high resolution roll angle measurement of linear displacement stages is developed theoretically and tested experimentally. The new optical configuration is based on a special differential plane mirror interferometer, a wedge prism assembly, and a wedge mirror assembly. The wedge prisms assembly is used as a roll angle sensor, which converts roll angle to the changes of optical path. The special interferometer, composed a polarization splitter plane, a half wave plate, a beam splitter, a retro-reflector and a quarter wave plate, is designed for high resolution measurement of the changes of the optical path. The interferometric beams are a completely common path for the adoption of the centrosymmetrical measurement structure, and the cross talk of the straightness, yaw, and pitch errors is avoided. The angle measurement resolution of the proposed method is 3.5 μrad in theoretical with a phase meter which has a resolution of 2π/512. The experimental result also shows the great stability and accuracy of the present roll angle measurement system. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 114, 440–451. Previous in vitro and in vivo investigations have suggested manganese (Mn2+) may play a role in pathogenesis through facilitating refolding of the normal cellular form of the prion protein into protease resistant, pathogenic isoforms (PrPSc), as well as the subsequent promotion of higher order aggregation of these abnormal conformers. To further explore the role of Mn2+ in pathogenesis, we undertook a number of studies, including an assessment of the disease modifying effects of chelation therapy in a well-characterized mouse model of prion disease. The di-sodium, calcium derivative of the chelator, cyclohexanediaminetetraacetic acid (Na2CaCDTA), was administered intraperitoneally to mice inoculated intra-cerebrally with either high or low-dose inocula, with treatment beginning early (shortly after inoculation) or late (at the usual mid-survival point of untreated mice). Analyses by inductively coupled plasma-mass spectrometry demonstrated brain Mn2+ levels were selectively reduced by up to 50% in treated mice compared with untreated controls, with copper, iron, zinc and cobalt levels unchanged. In mice administered high-dose inocula, none of the treatment groups displayed an increase in survival although western blot analyses of early intensively treated mice showed reduced brain PrPSc levels; mice infected using low-dose inocula however, showed a significant prolongation of survival ( p = 0.002). Although our findings support a role for Mn2+ in prion disease, further studies are required to more precisely delineate the extent of pathogenic involvement. [ABSTRACT FROM AUTHOR]

Existing technologies and methods for measuring transmitted wavefronts typically operate at only a few specific wavelengths. In this paper, we propose a new method for estimating the wavefront distortion of an optical transmission system in a broad bandwidth. We establish the relationship between the transmitted wavefront and wavelength, using Zernike fringe coefficients to represent the wavefront. From simulations of several different types of optical systems, we found that two formulas can be used to express Zernike-wavelength curves: the Conrady dispersion formula and a new formula that we have named the apochromatic characteristic formula. To reduce the influence of measurement errors on predictions, fitting method is biased in favor of simulation rather than experimental data. We illustrate the validity of this technique by reconstructing a wavefront transmitted at 671 nm using Zernike polynomials, demonstrating that the predicted wavefront is very similar to the wavefront measured experimentally. Using the Conrady formula, we illustrate that the wavefront of a monochromatic system can be predicted for any wavelength in a broad range, using data from three standard wavelengths. As Seidel coefficients correspond to Zernike coefficients, the relationship between optical aberration and wavelength detailed here can also be applied to areas, such as optical design, optical computing and adaptive optics. [ABSTRACT FROM AUTHOR]