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Cell penetrating peptides (CPPs) are short peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter) is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the blood-brain barrier (BBB) and enter brain cells. However, whether RVG can be used for genome editing in the brain has not been reported. In this work, we combined RVG with Cre recombinase for bacterial expression. The purified RVG-Cre protein cut plasmids in vitro and traversed cell membranes in cultured Neuro2a cells. By tail vein-injecting RVG-Cre into Cre reporter mouse lines mTmG and Rosa26lacZ, we demonstrated that RVG-Cre could target brain cells and achieve targeted somatic genome editing in adult mice. This direct delivery of the gene-editing enzyme protein into mouse brains with RVG is much safer than plasmid- or viral-based methods, holding promise for further applications in the treatment of various brain diseases. [ABSTRACT FROM AUTHOR]

Regulation of tumoral PD-L1 expression is critical to advancing our understanding of tumor immune evasion and the improvement of existing antitumor immunotherapies. Herein, we describe a CRISPR-based screening platform and identified ATXN3 as a positive regulator for PD-L1 transcription. TCGA database analysis revealed a positive correlation between ATXN3 and CD274 in more than 80% of human cancers. ATXN3-induced Pd-l1 transcription was promoted by tumor microenvironmental factors, including the inflammatory cytokine IFN-γ and hypoxia, through protection of their downstream transcription factors IRF1, STAT3, and HIF-2α. Moreover, ATXN3 functioned as a deubiquitinase of the AP-1 transcription factor JunB, indicating that ATNX3 promotes PD-L1 expression through multiple pathways. Targeted deletion of ATXN3 in cancer cells largely abolished IFN-γ– and hypoxia-induced PD-L1 expression and consequently enhanced antitumor immunity in mice, and these effects were partially reversed by PD-L1 reconstitution. Furthermore, tumoral ATXN3 suppression improved the preclinical efficacy of checkpoint blockade antitumor immunotherapy. Importantly, ATXN3 expression was increased in human lung adenocarcinoma and melanoma, and its levels were positively correlated with PD-L1 as well as its transcription factors IRF1 and HIF-2α. Collectively, our study identifies what we believe to be a previously unknown deubiquitinase, ATXN3, as a positive regulator for PD-L1 transcription and provides a rationale for targeting ATXN3 to sensitize checkpoint blockade antitumor immunotherapy [ABSTRACT FROM AUTHOR]

In the modern multishaft gas turbine engines, orifice is an important throttling element, and the discharge coefficient of rotating orifices may vary considerably depending on the operating conditions, the geometry, and surrounding environment. The influences of the rotating number and the pressure ratio on the rotating orifices' flow characteristics are investigated in this study. Besides, the effects of confined space, wall inclination angle (α), and the angle between the axis of orifice and the disk wall normal (β) are also analyzed statistically. It is found that the rotating number has a significant effect on the discharge coefficient. As the rotating number increases from 0 to 0.6, the discharge coefficient reduces by about 47.88%. When rotating number is 0.74 and pressure ratio is 1.10, the discharge coefficient can be improved by 16.88% with α changes from 90 deg to 180 deg. The parameter, β, affects discharge coefficient slightly in rotating condition. However, the maximum discharge coefficient is achieved with β = 0 deg in the static condition. The results also show that a confined space weakens the effect of rotation and changes the air flow direction in the inlet chamber, which also has a positive impact on the discharge coefficient. In the current research, it is found that there is a significant difference between the traditional empirical formulas used in the literature and the fitting result. By modifying the incidence angle and taking account of the influence of the angle of inclination, the maximum error was reduced from 56.79% to 3.16%. [ABSTRACT FROM AUTHOR]

Gas chromatography (GC) and gas chromatography-Fourier transform infrared spectrometry (GC-FTIR) were applied to the analysis of high boiling residue from the dry gas synthesized ethyl benzene distillation tower bottom. On the basis of database searching, the main component of the residue was identified as diphenyl methane. Gas chromatography coupled with mass spectrometry (GC-MS) was utilized to confirm this result and identify the other components, which are mainly 1,1-diphenylethane, polyalkyl benzene, and alkyl naphthalene compounds. The difference in sensitivity of GC-FTIR and GC-MS was compared. [ABSTRACT FROM AUTHOR]

Objective: To explore the feasibility and safety of ambulatory mPCNL (mini percutaneous nephrolithotomy) on upper urinary tract calculi.Methods: Clinical data of 18 patients received ambulatory mPCNL during Aug. 2017 to Jan. 2018 and 23 patients treated with routine inpatient mPCNL of the corresponding period were collected. All the patients included received 16Fr channel PCNL under the guidance of Doppler ultrasound. A 6Fr double J stent was placed in the ureter for internal drainage, and either an indwelling 14Fr open nephrostomy tube was placed or the puncture channel was filled with absorbable hemostatic materials alone, depends on the bleeding condition of the puncture channel and the intraoperative conditions. Preoperative parameters and surgery time, complications, total hospitalization costs and hospital stay time between the two groups were compared.Results: Preoperative parameters regarding age (P=0.057), sex distribution (P=0.380), ASA score (P=0.388), Calculi CT value (P=0.697), and the S.T.O.N.E. score (P=0.122) were comparable between the two groups. Maximum diameter of calculi (cm) of the conventional hospitalization group, however, was larger than the ambulatory surgery group (P=0.041). There were no significant differences in the mean surgery time (P=0.146), postoperative hemoglobin drop (P=0.865), Calculi-free rate on the next day after surgery (P=0.083) and postoperative fever rate (P=0.200) between the two groups. With regard to tubeless rate (P<0.001), total hospitalization costs (P=0.003) and hospital stay time (P<0.001), there were significant advantage favored ambulatory mPCNL.Conclusions: For patients with simple upper urinary tract calculi and relatively good performance status, ambulatory mPCNL is feasible as it's equally safe and efficient as compared with routine inpatient mPCNL. Moreover, ambulatory mPCNL decreases hospitalization costs and hospital stay time. Nevertheless, perioperative management should be carefully conducted, and well-designed studies are warranted. [ABSTRACT FROM AUTHOR]

Background: There are several positions in the operation of percutaneous nephrolithotomy (PCNL), such as prone position, supine position, flank position, and modified supine position for PCNL, but the supine and prone positions are the main two choices for several years. However, there is still discrepancy on the optimal position for PCNL. Therefore, we performed this meta-analysis to evaluate safety and efficacy of the supine versus the prone position in PCNL for renal calculi. Methods: We searched MEDLINE, SCOPUS, and the Cochrane database libraries to look for relevant studies. All eligible controlled trials comparing supine versus prone positions for treating renal calculi were included in the meta-analysis. The main outcome of efficacy (stone-free rate, mean operative time, and hospitalization time) and safety (complication, blood transfusions) were assessed by using Review Manager 4.2 software. We calculated the estimate of effect associated with the two positions according to the heterogeneity using random-effects or fixed-effects models. Results: Thirteen studies (six randomized controlled trials and seven retrospective studies) with a total of 6881 patients contributed to this meta-analysis. The meta-analysis indicated/suggested that PCNL in the prone position was associated with a higher rate of stone clearance than PCNL in the supine position (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.65, 0.84; p < 0.00001). A shorter mean operative time was observed in the supine groups (weighted mean difference [WMD]: -18.27; 95% CI: -35.77, -0.77; p = 0.04). Compared with the prone position, there was also a lower incidence of blood transfusions in the supine groups (WMD: 0.73; 95% CI: 0.56, 0.95; p = 0.02). No difference was observed between the positions with regard to the hospital stay (WMD: -0.14; 95% CI: -0.76, 0.47; p = 0.65) and complications (OR: 0.88; 95% CI: 0.76, 1.02; p = 0.10). Conclusion: Compared with the prone position, the PCNL in the supine position has a slightly lower rate of stone clearance, albeit shorter mean operative time, and lower incidence of blood transfusions. The meta-analysis suggests that the PCNL in the supine position is a promising alternative. [ABSTRACT FROM AUTHOR]

Gravimetric equilibrium isotherms, thermodynamic parameters, and diffusion of p-xylene in silicalite-1 were investigated at several temperatures using an intelligent gravimetric analyzer (IGA). Both plateau and hysteresis loops appeared in the isotherms obtained at 323 and 343 K, respectively. Heat of sorption ( Qst), free energy change (Δ G), entropy change (Δ S), and entropy ( Sa) of the adsorbed phase at various sorption coverages were determined from the adsorption isotherms. The diffusion coefficients at different loadings were also calculated using Fick's equation. The calculated thermodynamic and kinetic parameters satisfactorily explain the adsorption process and isotherm features. [ABSTRACT FROM AUTHOR]

Zinc methanesulfonate is prepared and used as a catalyst in many esterification reactions of chloroacetic acid with nearly equimolar amounts of alcohols. The catalytic activity, reusability, and handling of the catalyst are found to be good. Some factors that affect the esterification reaction of chloroacetic acid with isopropanol are investigated. Under the conditions of 1.1:1 molar ratio of isopropanol to chloroacetic acid, 0.5 mol% of the catalyst (molar percent of chloroacetic acid), 2.5 h of reaction time, ca. 14 mol% of cyclohexane (molar percent of chloroacetic acid) as water-carrying agent, and the temperature 85–90°C, the yield of isopropyl chloroacetate is 96.2%. In most cases, the catalyst is reused six times without obvious loss of catalytic activity. [ABSTRACT FROM AUTHOR]

Multifrequency electrical impedance tomography (MFEIT) reconstructs the distribution of conductivity by exploiting the dependence of tissue conductivity on frequency. MFEIT can be performed on a single instance of data, making it promising for applications such as stroke and cancer imaging, where it is not possible to obtain a ‘baseline’ measurement of healthy tissue. A nonlinear MFEIT algorithm able to reconstruct the volume fraction distribution of tissue rather than conductivities has been developed previously. For each volume, the fraction of a certain tissue should be either 1 or 0; this implies that the sharp changes of the fractions, representing the boundaries of tissue, contain all the relevant information. However, these boundaries are blurred by traditional regularization methods using norm. The total variation (TV) regularization can overcome this problem, but it is difficult to solve due to its non-differentiability. Because the fraction must be between 0 and 1, this imposes a constraint on the MFEIT method based on the fraction model. Therefore, a constrained optimization method capable of dealing with non-differentiable problems is required. Based on the primal and dual interior point method, we propose a new constrained TV regularized method to solve the fraction reconstruction problem. The noise performance of the new MFEIT method is analysed using simulations on a 2D cylindrical mesh. Convergence performance is also analysed through experiments using a cylindrical tank. Finally, simulations on an anatomically realistic head-shaped mesh are demonstrated. The proposed MFEIT method with TV regularization shows higher spatial resolution, particularly at the edges of the perturbation, and stronger noise robustness, and its image noise and shape error are 20% to 30% lower than the traditional fraction method. [ABSTRACT FROM AUTHOR]

The applications of total variation (TV) algorithms for electrical impedance tomography (EIT) have been investigated. The use of the TV regularisation technique helps to preserve discontinuities in reconstruction, such as the boundaries of perturbations and sharp changes in conductivity, which are unintentionally smoothed by traditional norm regularisation. However, the non-differentiability of TV regularisation has led to the use of different algorithms. Recent advances in TV algorithms such as the primal dual interior point method (PDIPM), the linearised alternating direction method of multipliers (LADMM) and the spilt Bregman (SB) method have all been demonstrated successful EIT applications, but no direct comparison of the techniques has been made. Their noise performance, spatial resolution and convergence rate applied to time difference EIT were studied in simulations on 2D cylindrical meshes with different noise levels, 2D cylindrical tank and 3D anatomically head-shaped phantoms containing vegetable material with complex conductivity. LADMM had the fastest calculation speed but worst resolution due to the exclusion of the second-derivative; PDIPM reconstructed the sharpest change in conductivity but with lower contrast than SB; SB had a faster convergence rate than PDIPM and the lowest image errors. [ABSTRACT FROM AUTHOR]