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Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied. To address this, we have established an orthotopic mouse model for study that recapitulates the aggressive clinical progression of radiorecurrent prostate cancer. Radiorecurrent DU145 cells which survived conventional fraction (CF) irradiation were orthotopically injected into the prostates of athymic nude mice and monitored with bioluminescent imaging. CF tumours exhibited higher take rates and grew more rapidly than treatment-naïve parental tumours (PAR). Pathohistological analysis revealed extensive seminal vesicle invasion and necrosis in CF tumours, recapitulating the aggressive progression towards locally advanced disease exhibited by radiorecurrent tumours clinically. RNA sequencing of CF and PAR tumours identified ROBO1, CAV1, and CDH1 as candidate targets of radiorecurrent progression associated with biochemical relapse clinically. Together, this study presents a clinically relevant orthotopic model of radiorecurrent prostate cancer progression that will enable discovery of targets for therapeutic intervention to improve outcomes in prostate cancer patients. [ABSTRACT FROM AUTHOR]

In today's increasingly specialized and fragmented sectoral chain, as well as increasingly close economic connections between regions, regional economic fluctuations caused by natural or human factors can be transmitted through the interregional economic network to external regions, causing losses. The assessment of external losses is the foundation for fully understanding the impact of emergencies and taking effective response measures. On the basis of the MRIO model, this paper constructs a model of the impact of the COVID-19 lockdown in Shanghai on the national economy and investigates the impact of artificial controls on the economies of various regions and sectors in China after the outbreak of the COVID-19 pandemic. The results indicate that the external losses caused by regional emergencies are much greater than the local losses. Second, the sectors with the greatest GDP losses caused by Shanghai's lockdown are wholesale and retail, whereas the sectors with the greatest decline are metal product manufacturing, machinery and equipment maintenance services. Finally, the impact of Shanghai's lockdown on other regions is not significantly related to their economic size or geographical location. [ABSTRACT FROM AUTHOR]

Traditional methods for characterizing friction in mechanical systems can be challenging, and the fitting accuracy often proves unsatisfactory. In contrast to conventional friction identification and numerical fitting approaches, we explore friction by analytically determining the normal forces emerging at contact surfaces. The associated joints are modeled as dual-mass systems with elastic transmission elements, which account for the effects of viscous damping and friction. When a joint experiences a constraint, the corresponding constraint force is computed as the solution to the Udwadia-Kalaba (U-K) equation. Employing a normal force, a closed-form expression for the friction torque is derived using the Stribeck friction model. This expression encompasses the magnitude at any instant of time without the need for auxiliary variables. A comparison between experimental and simulation results demonstrates that the friction analysis method proposed offers a reasonable and effective description. [ABSTRACT FROM AUTHOR]

Altered cardiac innate immunity is highly associated with the progression of cardiac disease states and heart failure. S100A8/A9 is an important component of damage-associated molecular patterns (DAMPs) that is critically involved in the pathogenesis of heart failure, thus considered a promising target for pharmacological intervention. In the current study, initially, we validated the role of S100A8/A9 in contributing to cardiac injury and heart failure via the overactivation of the β-adrenergic pathway and tested the potential use of paquinimod as a pharmacological intervention of S100A8/A9 activation in preventing cardiac dysfunction, collagen deposition, inflammation, and immune cell infiltration in β-adrenergic overactivation–mediated heart failure. This finding was further confirmed by the cardiomyocyte-specific silencing of S100A9 via the use of the adeno-associated virus (AAV) 9-mediated short hairpin RNA (shRNA) gene silencing system. Most importantly, in the assessment of the underlying cellular mechanism by which activated S100A8/A9 cause aggravated progression of cardiac fibrosis and heart failure, we discovered that the activated S100A8/A9 can promote fibroblast-macrophage interaction, independent of inflammation, which is likely a key mechanism leading to the enhanced collagen production. Our results revealed that targeting S100A9 provides dual beneficial effects, which is not only a strategy to counteract cardiac inflammation but also preclude cardiac fibroblast-macrophage interactions. The findings of this study also indicate that targeting S100A9 could be a promising strategy for addressing cardiac fibrosis, potentially leading to future drug development. [ABSTRACT FROM AUTHOR]

The mirror milling method applied in the machining of thin-walled workpieces can effectively reduce machining deformation and improve machining quality. However, it is challenging to model the collaborative relationship between the positions and orientations of dual-robot end effectors due to the coupled effects of multiple constraints. To address this issue, we propose a streamlined and adaptable system dynamics modeling technique based on the Udwadia-Kalaba (U-K) method that innovates and optimizes in terms of constraint extraction, transformation, and introduction. Firstly, based on the principle of similarity, we establish the unconstrained dynamic model of the system using the Denavit-Hartenberg (D-H) convention, Jacobian matrix, and Lagrangian equation. Simultaneously, in conjunction with the geometric constraints of the workpiece, the orientation and position cooperation constraints of the dual-robot end effectors are extracted and transformed based on the constraint-following theory. This transformation is applicable to general cases of varying curvature and thickness, resulting in an easily manageable form concerning four-point trajectory constraints. By integrating the unconstrained dynamic equation with the standardized constraint equation via the U-K method, we can construct the dynamic equation of the system under multiple-source constraints. Lastly, by employing SolidWorks and MATLAB for a joint simulation, we create a visual dynamic model of the system. The feasibility of the modeling method, in terms of cooperation, is demonstrated by processing a cylindrical thin-walled shell as the workpiece. [ABSTRACT FROM AUTHOR]

Five-axis linear commands are blended as the local smoothed toolpaths by inserting clothoid and airthoid splines at corners in five-axis CNC machining. The contour error is the bottleneck to achieve the precise dimension of the machined parts, when following the local smoothed toolpaths. This paper presents a contour error estimation and control method for the five-axis smoothed toolpaths with airthoid splines, according to the geometric characteristics of the toolpaths. The tool-tip contour error is analytically calculated based on the expression of the smoothed toolpaths. Consequently, the tool-orientation contour error is obtained by synchronizing the tool-orientation contour point with the tool-tip item based on the motion time through the designed time scale coefficient, when the toolpaths are scheduled by the time-synchronization scheme. Furthermore, a contour error compensation strategy is constructed to adaptively determine the compensator gain. It can be qualified to maximally eliminate the contour errors and steadily hold the control stability of the feed drives, in spite of the modeling error between the nominal and actual control models. The simulation and experiment results show that the estimation algorithm has higher accuracy than traditional methods, and the compensation strategy effectively eliminates the five-axis contour error. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether pre-treatment contrast-enhanced MRI could predict the therapeutic response of systemic treatment in advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective study enrolled 61 ICC participants with contrast-enhanced MRI before combined systemic therapy. Clinical characteristics and MRI features were compared between patients with and without therapeutic response by univariate and multivariate logistic regression analyses. Then, a combined MRI-based model and the nomogram were established based on the results of the multivariate analysis. The diagnostic performances of significant findings and the combined model were evaluated and compared. The progression-free survival (PFS) rates between patients with high and low combined index values were compared. Results: Thirty (49.18%) patients showed overall response after therapy. In multivariate analysis, tumor margin (odds ratio (OR) = 5.004, p = 0.014), T2 homogeneity (OR = 14.93, p = 0.019), and arterial peritumoral enhancement (OR = 5.076, p = 0.042) were independent predictive factors associated with therapeutic response. The C-index with the formulated nomogram incorporating the three independent imaging features was 0.828 (95% CI 0.710–0.913). Diagnostic characteristics of the combined index were superior to any single feature alone (p = 0.0007–0.0141). ICCs with high combined index values showed higher PFS rates than those with low values (χ2 = 13.306, p < 0.0001). Conclusions: Pre-treatment contrast-enhanced MRI can be used to predict therapeutic response in advanced ICC with systemic therapy. The combination model incorporating significant MRI features achieved an improved predictive value, which may play an important role in identifying appropriate therapeutic candidates. Key Points: • Contrast-enhanced MRI can predict response of systemic therapy in advanced ICC. • MRI features of tumor margin, T2 homogeneity, and arterial peritumoral enhancement are related to therapeutic response. • The combined MRI-based model may help to identify appropriate therapeutic candidates. [ABSTRACT FROM AUTHOR]

The accurate estimation and effective compensation of contour error are beneficial to the realization of high-speed and high-precision five-axis machining. And the movements of the five-axis trajectory can be synchronized by either curve parameter or motion time. This paper focuses on developing an on-line contour error estimation and compensation strategy for the five-axis local smoothed trajectory under motion time synchronization. First, to perform an on-line contour error estimation, the algorithms to find the contouring cutter location are proposed. Here, the contouring cutter location consists of the tool tip contouring point and tool orientation contouring vector. Without the construction of any frame, the segment of the smoothed trajectory where the tool tip contouring point is located is found by comparing the length of the projection of the tool tip actual point on the linear path. Then, depending on the type of this segment, two different ways to fine locate the tool tip contouring point are shown. In the meantime, the corresponding tool orientation contouring vector under motion time synchronization is obtained in the interpolation segment by the proposed rough and fine matching method. Second, as to the on-line contour error compensation, three compensators are designed to send the decoupled contour error estimation values back to the position loop, velocity loop, and current loop of each servo controller. Finally, simulation and experiment show that the proposed method can achieve high-precision on-line estimation and effective on-line compensation of contour errors for the trajectories under both curve parameter synchronization and time synchronization compared with the existing method. [ABSTRACT FROM AUTHOR]

From the perspective of supply chain, energy consumption is an aggregation of energy intensity, intermediate input ratio, and final demand. However, research on the role of intermediate input on energy consumption is rare. This paper disaggregates the complete demand model of China based on MRIO (multi-region input-output model) into final demands and intermediate demands, and applied a decomposition approach combining LMDI (logarithmic mean Divisia index) and SDA (structural decomposition analysis) to evaluate the contribution of intermediate intensity, integrating the respective advantages of SDA and LMDI. The results show that both domestic and international intermediated intensities promote China's energy consumption growth in most years. The reasons are as follows: (1) the intermediate efficiency enhanced; (2) the final consumption structure shifted toward the more complex pattern; (3) the market demanded more energy-intensive final goods. All effects are positive except the energy intensity effect. Based on the consistency in aggregation of LMDI, we found that the aggregation of international effects is bigger than the aggregation of domestic effects, illustrating that international factors are the main driving force of China's energy consumption. The research implies that the intermediate process deserves more attention for the mitigation of energy consumption and greenhouse gas emissions. Improvement of intermediate efficiency and structure will be effective. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficiency of plasma exchange (PE) add-on on optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD). Methods: Our ambispective, nonrandomized study was performed in Southwest Hospital, Southwest Eye Hospital, Army Medical University. We studied 31 consecutive NMOSD patients characterized by ON and hospitalized from September 2015 to May 2018. Their clinical features were assessed, and efficiency of PE add-on treatment in ON of NMOSD was evaluated. Correlation was assessed between the effect of steroid pulse therapy (SPT) and the number of ON episodes in NMOSD. Results: All 31 NMOSD patients accepted SPT; 15 patients of them accepted SPT and PE add-on. In these 15 patients, after PE add-on treatment, the patients' visual acuity was further significantly improved (P = 0.000, N = 23), including 3 no light perception (NLP) patients. After the treatment, the visual function recovered quickly in the first 2 months and then gradually slowed down; the visual function remained stable about 6 months later. The correlation coefficient between visual acuity improvement of SPT and the number of ON episodes was − 0.311 (P = 0.030, N = 49). Conclusion: One clinical feature of NMOSD can be repeated vision impairment. In NMOSD patients characterized by ON, efficacy of SPT is limited as the number of episodes increased, and PE add-on is more effective. Even though the visual acuity of NMOSD patients decreases to NLP during episodes, there is still a chance to restore vision by PE add-on treatment. [ABSTRACT FROM AUTHOR]

The present paper reported the spectroscopic behavior and thermal stability of Eu3+ activated BaGd2Si3O10 phosphors synthesized by high temperature solid state reaction. The X-ray diffraction (XRD) patterns revealed that as-prepared BaGd2Si3O10:xEu3+ phosphors consisted of single phase monoclinic structure. Under the excitation of 395 nm, Eu3+ ions showed five emission peaks around 578, 589, 613, 654 and 702 nm corresponding to the 5D0 → 7F0, 5D0 → 7F1, 5D0 → 7F2, 5D0 → 7F3 and 5D0 → 7F4 transitions, respectively. The θ value was calculated to be 6.68, which indicated that concentration quenching occurred due to dipole-dipole interactions. The critical distance (Rc) between activator ions was found to be 11.2 Å. Decay curve measurements were made to find excited state lifetime of Eu3+ ions. The dominant emission color of as-prepared phosphors was obtained by using CIE 1931 color chromaticity diagram. Further, thermal stability and activation energy for thermal quenching were also estimated for the optimal concentration phosphor to claim its applicability for near-UV based WLEDs. [ABSTRACT FROM AUTHOR]

Single phase yellow-emitting Dy3+ ions doped Ba2Gd5B5O17 phosphors were synthesized by solid-state reaction technique at high temperature. The phase identification and photoluminescence properties of as-prepared phosphors were characterized by X-ray diffraction patterns, excitation and emission spectra, decay curves and temperature-dependent luminescence spectral measurements. Under 276 and 354 nm near-UV excitations, the studied phosphors exhibited two intense emission bands in blue (486 nm) and yellow (575 nm) regions due to the magnetic dipole (4F9/2→6H15/2) and electric dipole (4F9/2→6H13/2) transitions, respectively. The optimal doping concentration of Dy3+ ions was found to be x = 0.07 for Ba2Gd5−xDyxB5O17 phosphors. Under 354 nm excitation, the color coordinates (x, y) of Ba2Gd4.93Dy0.07B5O17 phosphor were located in the yellow region of Commission International de I-Eclairage 1931 diagram and hence it can be used as a potential yellow component in the fabrication of white light-emitting diodes. Furthermore, the decay curves were fitted to double-exponential function to find the excited state lifetimes of Dy3+ ions. Besides, the temperature-dependent luminescence measurements were made to explore the thermal stability and activation energy of the concentration-optimized Ba2Gd4.93Dy0.07B5O17 phosphor. The results obtained from the present investigation were discussed in detail and compared with the similar reported literatures. [ABSTRACT FROM AUTHOR]

Novel red-emitting phosphors of Ca3Y(AlO)3(BO3)4 doped with different concentrations of Mn4+ were successfully synthesized by a high-temperature solid-state reaction method. Crystal composition, microstructure, and luminescence properties of samples were characterized by X-ray diffraction, scanning electron microscope, excitation and emission spectra, decay lifetimes and temperature-dependent photoluminescence spectra. The emission spectra exhibited a strong deep-red emission band in the wavelength range of 625-750 nm with a maximum at 678 nm. The optimal doping concentration of Mn4+ was about 0.1 mol%. Under 325 nm excitation, the CIE chromaticity coordinates of Ca3Y(AlO)3(BO3)4:0.1%Mn4+ sample were (0.704, 0.296). In addition, the concentration quenching mechanism was dominated by a dipole-dipole interaction for the Mn4+ activators. The value of the activation energy Ea was calculated to explain thermal quenching. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRs) are involved in the regulation of many processes that contribute to malignancy, including cell proliferation, radiation resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated in breast cancer, remains unclear.Methods: We examine the association of miR-330-3p with distant relapse-free survival in the Oxford cohort of breast cancer patients. We also study miR-330-3p function using in vitro invasion and ex ovo metastasis assays. Using in vitro luciferase assays, we validate a novel target gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown followed by in vitro invasion assays. Lastly, we examine the expression profile of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets using Oncomine Platform as well as distant relapse-free and overall survival of patients in the Helsinki University breast cancer data set according to CCBE1 expression status.Results: miR-330-3p is enriched in breast cancer, and higher levels of miR-330-3p expression are associated with lower distant relapse-free survival in a cohort of breast cancer patients. Consistent with these observations, overexpression of miR-330-3p in breast cancer cell lines results in greater invasiveness in vitro, and miR-330-3p-overexpressing cells also metastasise more aggressively ex ovo. We identify CCBE1 as a direct target of miR-330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity. Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its loss is associated with reduced distant relapse-free and overall survival.Conclusions: We show for the first time that miR-330-3p targets CCBE1 to promote invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers in breast cancer. [ABSTRACT FROM AUTHOR]

The development of efficient sub-10 nm ultrasmall upconversion nanoparticles will open the door to the exciting application in biological labelling and imaging. In this paper, we demonstrated a facile method for the synthesis of monodisperse sub-10 nm hexagonal-phased LaF nanoparticles doped with upconverting lanthanide ions (Yb/Ln, Ln = Er, Tm, and Ho). The particle size of the as-synthesized LaF nanoparticles can be tuned by varying the preparation temperature. Upon excitation at 980 nm, the LaF:Yb/Ln nanoparticles showed intense upconversion emissions, and the colour output can be precisely modulated by changing the species and concentration of the lanthanide activators. In order to further enhance the upconversion emission intensity of the ultrasmall LaF:Yb/Ln nanoparticles, we adopted the strategy of core-shell nanostructured design to minimize the surface quenching effect. After coating an inert LaF shell, a maximum ninefold enhancement in upconversion luminescence was achieved under 980 nm excitation. These as-prepared lanthanide-doped LaF upconversion nanoparticles may find promising applications in biomedicine fields as luminescent nanoprobes. [ABSTRACT FROM AUTHOR]

To evaluate the accuracy and feasibility of right ventricular function parameters measurement using 320-slice volume cardiac CT. Retrospective analysis of 50 consecutive patients (23 men, 27 women) with suspected pulmonary diseases was performed in electrocardiogram (ECG)-gated cardiac CT and cardiac magnetic resonance (CMR). Parameters including right ventricular end-diastolic volume (RVEDV), right ventricular end- systolic volume (RVESV), right ventricular stroke volume (RVSV), right ventricular cardiac output (RVCO), and right ventricular ejection fraction (RVEF) were semi-automatically and separately calculated from both CT and CMR data. Significant difference between measurements was measured by paired t test and two-variable linear regression analysis with Pearson's correlation coefficient. Bland-Altman analysis was performed in each pair of parameters. There was little variability between the measurements by the two observers (kappa = 0.895-0.980, P < 0.05). There was good correlation between all parameters obtained by CT and CMR ( P < 0.001): RVEDV (108.5 ± 21.9 ml, 113.5 ± 24.8 ml, r = 0.944), RVESV (69.8 ± 33.4 ml, 73.2 ± 35.4 ml, r = 0.972), RVSV (39.0 ± 13.2 ml, 40.2 ± 13.3 ml, r = 0.977), RVCO (2.6 ± 0.7 l, 2.6 ± 0.7 l. r = 0.958), RVEF (38.8 ± 19.1 %, 39.1 ± 19.3 %, r = 0.990), and there was no significant difference between CT and CMR measurements in RVEF (n = 50, t = −0.677, P > 0.05). 320-slice volume cardiac CT is an accurate non-invasive technique to evaluate RV function. [ABSTRACT FROM AUTHOR]

The article discusses research on the ability of red phosphor to transition white light emitting diodes (LED) into new form. It references a study by Philipp Pust and colleagues in the 2014 issue of "Nature Materials." Topics covered include the use of white LED as an attractive solution for illumination as well as energy efficiency of the LED.

: It has recently become more recognized that renal diseases in adults can originate from adverse intrauterine (maternal) environmental exposures. Previously, we found that prenatal lipopolysaccharide (LPS) exposure can result in chronic renal inflammation, which leads to renal damage in older offspring rats. To test whether prenatal inflammatory exposure predisposes offspring to renal damage, a mouse model of oral adenine consumption-induced chronic kidney disease (CKD) was applied to offspring from prenatal LPS-treated mothers (offspring-pLPS) and age-matched control offspring of prenatal saline-treated mothers (offspring-pSaline). We found that offspring-pLPS mice presented with more severe renal collagen deposition and renal dysfunction after 4 weeks of adenine consumption than sex- and treatment-matched offspring-pSaline controls. To illustrate the underlying molecular mechanism, we subjected offspring-pLPS and offspring-pSaline kidneys to genome-wide transcriptomic analysis. Bioinformatic analysis of the sequencing data, together with further experimental confirmation, revealed a strong activation of the PERK-eIF2α-ATF4-mediated unfolded protein response (UPR) in offspring-pLPS kidneys, which likely contributed to the CKD predisposition seen in offspring-pLPS mice. More importantly, the specific eIF2α-ATF4 signaling inhibitor ISIRB was able to prevent adenine-induced CKD in the offspring-pLPS mice. Our findings suggest that the eIF2α-ATF4-mediated UPR, but not PERK, is likely the major disease-causing pathway in prenatal inflammatory exposure-induced CKD predisposition. Our study also suggests that targeting this signaling pathway is a potentially promising approach for CKD treatment. [ABSTRACT FROM AUTHOR]