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To describe a novel modification of technique to improve efficacy of robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) in infants.Between April 2017 and July 2019, sixteen infants with primary obstructive megaureter (POM) (Age range: 4-12 months) underwent robot-assisted ureteral reimplantation were reviewed in this series. In addition to the conventional Lich-Gregoir technique, the detrusor tunnel has been extended to the mobilized anterior bladder wall to guarantee sufficient tunnel length/ureter diameter ratio and avoid ureteral angulation. All patients underwent repeated ultrasound, diuretic renal dynamic imaging and voiding cystourethrography (VCUG) perioperatively and the outcomes were documented.All operations were completed with robotic assisted approach without conversion. Bilateral and unilateral reimplantation were respectively performed in two and fourteen patients. The mean operative time was 115.0 ± 19.5 min and the mean blood loss was 10.0 ± 1.8 ml. There were no high-grade complications (III-IV on Clavien-Dindo classification) except for one patient. The distal ureteric diameter was reduced from pre operative 1.7 ± 0.5 to 0.6 ± 0.5 cm 6 months post operatively (p 0.05). One child (6.3%) required the second reimplantation for stenosis. The overall operative success rate was 94.4% (17 of 18 ureters) with a mean follow-up of 15.9 ± 7.4 months with no flux detected.Our preliminary experience suggests that our modified robot-assisted laparoscopic extravesical ureteral reimplantation is feasible in infants with good results.

This short Perspective article presents an overview of the discovery of topological $\pi$ modes as well as their physical significance in quantum computing and the understanding of an exotic phase of matter, i.e., the Floquet time crystal. The recent proposals of $2\pi/k$ modes as the generalizations of $\pi$ modes are further elucidated., Comment: 5 pages, 1 figure. Published in Science Bulletin

Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. The tight junction protein CLDN4 is closely related to the development of various epithelial cell carcinomas. However, whether CLDN4 contributes to AML development remains unclear. For the first time, we found that expression of CLDN4 is aberrantly up-regulated in AML cells. Knockdown of CLDN4 expression resulted in a dramatic decreased cell growth, elevated apoptosis of AML cells. Further, we revealed that knockdown of CLDN4 inhibits mRNA expression of PIK3R3 and MAP2K2, thus suppresses activation of AKT and ERK1/2. More importantly, activating AKT branch by SC79 partially compromised CLDN4 knockdown induced cell viability inhibition. In addition, we found that higher expression of CLDN4 is connected to worse survival and is an independent indicator of shorter disease free survival (DFS) in AML patients. Together, our results indicate that CLDN4 contributes to AML pathogenesis, and suggests that targeting CLDN4 is a promising option for AML treatment.

The crystallization behavior, microstructure, crystalline phases, microhardness, coefficient of thermal expansion (CTE), and wetting behavior of Nd2O3-Al2O3-SiO2 (NAS) glass ceramics with different TiO2 content were investigated. The results show that the content of crystals increases and the size of crystals decreases with the increase of TiO2 content. Moreover, the formation of Nd2SiO5 leads to the increase and the precipitation of Al6Si2O13 results in the decrease in the CTE value of NAS glass ceramics. As a result, the CTE of NAS glass ceramics can be controlled in the range of 4.2–9.2 × 10−6/℃. These values are suitable for matching bonding to most ceramics with different CTE. Indeed, contact angle measurement demonstrates that the NAS glasses with 3 %, 6 % and 9 % TiO2 possess excellent wettability on the Al2O3, ZrO2 and zirconia toughened alumina (ZTA) ceramic, respectively.

Higher-order topological insulators (HOTIs) are systems with topologically protected in-gap boundary states localized at their $(d-n)$-dimensional boundaries, with $d$ the system dimension and $n$ the order of the topology. This work proposes a rather universal dynamics-based characterization of one large class of $Z$-type HOTIs without specifically relying on any symmetry considerations. The key element of our innovative approach is to connect quantum quench dynamics with nested configurations of the so-called band inversion surfaces (BISs) of momentum-space Hamiltonians as a sum of operators from the Clifford algebra (a condition that can be relaxed), thereby making it possible to dynamically detect each and every order of topology on an equal footing. Given that experiments on synthetic topological matter can directly measure the winding of certain pseudospin texture to determine topological features of BISs, the topological invariants defined through nested BISs are all within reach of ongoing experiments. Further, the necessity of having nested BISs in defining higher-order topology offers a unique perspective to investigate and engineer higher-order topological phase transitions., Comment: 15 pages and 7 figures in total. Comments are welcome

Sliding wear-induced nanolayering and its positive impact on wear resistance have been observed in conventional binary alloys with a matrix of high stacking fault energy (SFE), but this concept has never been reported in high-entropy alloys (HEAs) with low SFE. Here, we design and fabricate a (CoCrFeNi)90Ag10 HEA, consisting of a face-center-cubic (fcc) CoCrFeNi HEA matrix with low SFE and uniformly dispersed Ag precipitates. In comparison with CoCrFeNi, a significant reduction in friction and wear was found in (CoCrFeNi)90Ag10 HEA through the spontaneous formation of nanolayered subsurface microstructure during wear. The finding suggests a novel approach for designing HEAs that can achieve low friction and wear.

Background The aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). Methods This retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. Results The model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75–0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. Conclusion Our study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

A Si-substituted rhodamine based water-soluble fluorescent probe bearing a tetrathia-azacrown was designed for fluorescence imaging of Cu+ with substantial affinity and selectivity. In physiological condition, the developed probe with outstanding water-solubility exhibits ultrahigh sensitivity to Cu+, ensuring the reliable fluorescence imaging in vivo.

In this paper, a novel Dy2O3-Al2O3-SiO2 (DAS) glass ceramic was designed and prepared for joining zirconia toughened alumina (ZTA) ceramic. The crystallization, thermal expansion behavior and wetting behavior of the DAS glass filler were studied. The effect of cooling rate and joining temperature on the microstructure and flexural strength of joints was investigated. The results show that slow cooling rate (15 °C/min) leads to crystallization of brazing seam, which causes the formation of pores in the joints due to the large density difference between the glass and the crystalline phases. The dissolution of ZrO2 from ZTA substrate into the filler during joining process improves the mismatch of the coefficient of thermal expansion (CTE) between the brazing seam and substrate. The maximum flexural strength of 535 MPa is obtained when the joining temperature and cooling rate are 1475 °C and 50 °C/min, respectively.

Titanium alloys have been widely used for medical devices and structural applications. However, conventional titanium alloys often suffer from low resistance to wear, particularly at elevated temperatures. Herein, an equiatomic TiMoNb compositionally complex alloy (CCA) is shown to exhibit wear resistance comparable to alumina at room temperature (RT). Even at 600 °C, the alloy still shows an extremely low wear rate of the order of 10−6 mm3/(N·m). The remarkable wear resistance is achieved via tuning the interfacial structure and chemistry in TiMoNb CCA, including nanostructuring, titanium segregation at the grain boundaries, and the formation of a high density of nanoscale coherent Ti-rich precipitates with cube-on-cube orientation relationship with the ultrafine-grained matrix. The present results provide significant insights into the design of novel alloys for service in harsh environments.

Purpose Social contagion among physicians may affect the dissemination of innovative and high-value cancer care. We applied social contagion theory to investigate the role of physician peer influence on the use of short courses of external beam radiation therapy (EBRT) for patients with breast cancer. Methods and Materials Using a cohort of Medicare beneficiaries with breast cancer, we constructed physician peer groups based on patient-sharing relationships. Outcomes were a patient’s receipt of (1) moderately hypofractionated adjuvant EBRT after breast-conserving surgery and (2) short-course palliative EBRT for bone metastases. Using a longitudinal design, we used mixed-effects logistic regression to examine the association between physician peer group rate of short-course EBRT in 2011 to 2012 (T1) and patients’ receipt of short-course EBRT in 2013 to 2014 (T2). Results During T2, a total of 17,248 patients received adjuvant therapy (32.3% moderately hypofractionated) from 3235 physicians in 1202 physician peer groups. Compared with patients treated within peer groups in which no moderately hypofractionated adjuvant EBRT was used in T1, patients treated by a physician in a peer group with higher T1 use of moderately hypofractionated adjuvant EBRT were more likely to receive moderately hypofractionated adjuvant EBRT in T2 (adjusted odds ratio = 2.03; 95% confidence interval, 1.62-2.54, vs adjusted odds ratio = 2.61; 95% confidence interval, 2.04-3.35, for peer groups where 21%-46% and 47%-100% of radiation oncologists used moderately hypofractionated adjuvant EBRT in T1, respectively, compared with peer groups with no use of moderately hypofractionated adjuvant EBRT). In contrast, there was no significant relationship between T1 peer group use and T2 receipt of short-course palliative EBRT for bone metastases. Conclusions Physician peer groups significantly influenced use of short-course EBRT in adjuvant therapy but not in palliative therapy for patients with breast cancer.

Determination of amphetamine-type drugs (ATSs) in urine and wastewater is a simplified approach for the widespread monitoring of ATSs abuse. To improve the sensitivity of the analytical methods, molecularly imprinted polymers (MIPs) based solid-phase extraction (SPE) pretreatment attracted great attention in this field. Generally, smaller particle sizes and more uniform morphology of the MIPs could provide higher detection sensitivity. Our previous works showed reflux precipitation polymerization (RPP) is a method for synthesizing monodispersed MIPs with small particle size. However, synthesis of uniform spherical MIPs towards a group of targets has never been reported. Therefore, in the present work, MIPs towards a group of ATSs were synthesized via RPP with a pseudo template for the first time. After screening potential pseudo-templates, N-methylphenylethylamine (MPEA) was selected as the optimal pseudo-template. MPEA-MIPs were characterized by scanning electron microscope (SEM), FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS) spectra. Adsorption isotherms, adsorption kinetics and selectivity were evaluated, and the experimental results indicated that the MPEA-MIPs possessed good selectivity and adsorption property towards ATSs. After optimization of the MIP-SPE procedure, the MIP-SPE cartridges were then coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS) for determination of ATSs. The evaluation results showed that MIP-SPE-LC-MS/MS displayed good linearity (R

Acute lung injury (ALI) is a challenging clinical syndrome that manifests as an acute inflammatory response. Schisandrin B (Sch B), a bioactive lignan from Schisandra genus plants, has been shown to suppress inflammatory responses and oxidative stress. However, the underlying molecular mechanisms have remained elusive.This study performed an in-depth investigation of the anti-inflammatory mechanism of Sch B in macrophages and in an animal model of ALI.qPCR array was used to probe the differential effects and potential target of Sch B. ALI was induced by intratracheal administration of LPS in experimental mice with or without Sch B treatment.Our studies show that Sch B differentially modulates inflammatory factor induction by LPS in macrophages by directly binding myeloid differentiation response factor-88 (MyD88), an essential adaptor protein in the toll-like receptor-4 (TLR4) pathway. Sch B spares non-MyD88-pathways downstream of TLR4. Such inhibition suppressed key signaling mediators such as TAK1, MAPKs, and NF-κB, and pro-inflammatory factor induction. Pull down assay using biotinylated-Sch B validate the direct interaction between Sch B and MyD88 in macrophages. Treatment of mice with Sch B prior to LPS challenge reduced inflammatory cell infiltration in lungs, induction of MyD88-pathway signaling proteins, and prevented inflammatory cytokine induction.In summary, our studies have identified MyD88 as a direct target of Sch B for its anti-inflammatory activity, and suggest that Sch B may have therapeutic value for acute lung injury and other MyD88-dependent inflammatory diseases.

CaO–Al2O3–SiO2–TiO2 glass ceramic filler with high crystallinity was used for joining alumina ceramic. The influence of joining temperature and crystallization treatment on the microstructure and flexural strength of joints was studied. The results demonstrated that a joining temperature higher than the melting temperature of crystals was essential to obtain dense joints. Furthermore, the formation of CaAl2Si2O8 at the alumina/glass filler interface decreased the flexural strength of joints due to the mismatch of coefficient of thermal expansion (CTE) between CaAl2Si2O8 and substrate. The maximum flexural strength of 256 MPa at room temperature was achieved when the joining temperature was 1260 °C. After crystallization treatment, a large number of fine CaTiSiO5 was precipitated in the brazing seam. The flexural strength of joints after crystallization at room temperature was 221 MPa, and increased to 242 MPa at 800 °C. These results can be attributed to the change of CTE value of the brazing seam.

This project was supported by the National Key Research and Development Program of China (No. 2019YFA0708704). The authors would like to thank all editors and anonymous reviewers for their comments and suggestions. All the synthetically generated data and digitized outcrop maps are available online (https://doi.org/10.4121/14865096.v2)

Aberrant activation of epidermal growth factor receptor (EGFR) plays a pivotal role in cancer initiation and progression and has gained attention as an anticancer drug target. EGFR monoclonal antibodies have been canonically used in non-small cell lung cancer (NSCLC) treatment. However, a basal level of ligand-independent EGFR signaling pro-survival properties limit the clinical efficacy of EGFR monoclonal antibodies. Therefore, targeting EGFR by inducing degraders is a promising approach towards improving therapeutic efficacy and augmenting the effect of nimotuzumab. Here we describe rational discovery of OTP-3, an oxidized (-)-Epigallocatechin gallate (EGCG) derivative that elicits potent anticancer activity in EGFR wild type NSCLC. Mechanistic studies disclosed that OTP-3 directly binds to EGFR extracellular domain decreases EGF and EGFR binding affinities by combination with nimotuzumab. Molecular docking studies revealed that OTP-3-EGFR is a very stable complex. Further analyses showed that nimotuzumab combined with OTP-3 resulted in significantly promoted EGFR degradation and repressed downstream survival pathways. Accordingly, OTP-3 combined with nimotuzumab significantly inhibits tumor growth through degrading EGFR in vivo. Thus, OTP-3 can also serve as an effective therapeutic agent in NSCLC where it can augment the effects of nimotuzumab, a valuable property for combination agents.

Activation of the innate immune system through toll-like receptors (TLRs) has been repeatedly demonstrated in non-alcoholic fatty liver disease (NAFLD) and several TLRs have been shown to contribute. Myeloid differentiation primary response 88 (MyD88) is as an adapter protein for the activation of TLRs and bridges TLRs to NF-κB-mediated inflammation in macrophages. However, whether myeloid cell MyD88 contributes to NAFLD are largely unknown. To test this approach, we generated macrophage-specific MyD88 knockout mice and show that these mice are protected against high-fat diet (HFD)-induced hepatic injury, lipid accumulation, and fibrosis. These protective effects were associated with reduced macrophage numbers in liver tissues and surpassed inflammatory responses. In cultured macrophages, saturated fatty acid palmitate utilizes MyD88 to activate NF-κB and induce inflammatory and fibrogenic factors. In hepatocytes, these factors may cause lipid accumulation and a further elaboration of inflammatory cytokines. In hepatic stellate cells, macrophage-derived factors, especially TGF-β, cause activation and hepatic fibrosis. We further show that pharmacological inhibition of MyD88 is also able to reduce NAFLD injury in HFD-fed mice. Therefore, our study has provided empirical evidence that macrophage MyD88 participates in HFD-induced NAFLD and could be targeted to prevent the development and progression of NAFLD/NASH.

Direct electrochemical reduction of CO2 to multicarbon products is highly desirable, yet challenging. Here, we present a potentiostatic pulse-electrodeposition of high-aspect-ratio CuxAuy nanowire arrays (NWAs) as high-performance electrocatalysts for the CO2 reduction reaction (CO2RR). The surface electronic structure related to the Cu:Au ratio in the CuxAuy NWAs could be facilely modulated by controlling the electrodeposition potential and the as-fabricated CuxAuy NWAs could be directly used as the catalytic electrode for the CO2RR. The morphology of the high-aspect-ratio nanowire array significantly lowers the onset potential of the alcohol formation due to the diffusion-induced enhancement of the local pH and CO concentration near the nanowire surface. Besides, the properly adjusted surface electronic structure of the CuxAuy NWA enables the adsorption of CO and facilitates the subsequent CO reduction to ethanol via the C-C coupling pathway. Owing to the synergistic effect of morphology and electronic structure, the optimized CuxAuy NWA selectively reduces CO2 to ethanol at low potentials of −0.5–−0.7 V vs. RHE with a highest Faradaic efficiency of 48%. This work demonstrates the feasibility to optimize the activity and selectivity of the Cu-based electrocatalysts toward multicarbon alcohols for the CO2RR via simultaneous adjustment of the electronic structure and morphology of the catalysts.

Background Dual-energy computed tomography (DECT) can differentiate iodine from other materials through the material decomposition technique. The purpose of this study was to compare the diagnostic performance of DECT-derived iodine concentration (mg/ml) with conventional enhancement measurements (HU), in detecting left atrial appendage (LAA) thrombi and differentiating thrombi from circulatory stasis in atrial fibrillation (AF) patients referred for catheter ablation. Methods Consecutive patients were prospectively recruited and scanned using a third-generation dual-source CT system in dual-energy mode. Regions of interest were placed inside the filling defect in the LAA and ascending aorta (AA) of the same sections, to determine iodine concentration and the LAA/AA HU ratio. The diagnostic performance of iodine concentration and LAA/AA HU ratios were compared using transesophageal echocardiography (TEE) as the reference standard. Results Among 302 patients, 10 thrombi and 27 cases with spontaneous echo contrast (SEC) were detected by TEE. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of iodine concentration were superior to those of LAA/AA HU ratios (iodine concentration: 99.7%, 100%, 99.7%, 90.9%, and 100% vs. LAA/AA HU ratios: 96.0%, 100%, 95.9%, 45.5%, and 100%) in detecting LAA thrombi. The area under the receiver operating characteristic curve of iodine concentration (0.996; 0.898–1.000) was significantly larger than that of the LAA/AA HU ratio (0.881; 0.733–0.964) in differentiating thrombi from circulatory stasis (p Conclusions DECT-derived iodine concentration was associated with improved diagnostic accuracy compared with conventional enhancement measurements in detecting LAA thrombi and differentiating thrombi from circulatory stasis in AF patients.