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Reliability‐based design optimization (RBDO) traditionally relies primarily on high‐fidelity and computationally expensive simulations to search for and evaluate design solutions. However, significant disparities could emerge for complex nonlinear behavior that are challenging for numerical modeling. In contrast to mitigating the impact of inaccurate numerical modeling through optimization algorithms, laboratory experiments realistically capture the complex nonlinear behavior of structures or their components. Real‐time hybrid simulation (RTHS) is widely considered as an efficient and cost‐effective technique for integrating numerical modeling with experimental testing for structural response evaluation. This study proposes an innovative framework that utilizes RTHS for the performance assessment of candidate designs to enable RBDO of structures subjected to pulse‐like ground motions. RTHS tests are conducted to physically evaluate structural responses through realistically replicating complex nonlinear behavior of experimental substructures. This study introduces a novel penalty function‐based efficient global optimization (P‐EGO) method to minimize the required number of laboratory tests through surrogating the response quantities of interest derived from RTHS. The proposed framework is experimentally evaluated for design optimization of a two‐story four‐bay steel moment‐resisting frame with self‐centering viscous dampers subjected to pulse‐like ground motions. The results demonstrate innovative application of RTHS in dynamic optimal design to account for uncertainties. It offers an effective and efficient alternative for traditional RBDO through pure computational simulation, particularly when structural components pose challenges for numerical modeling. [ABSTRACT FROM AUTHOR]

The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population. [ABSTRACT FROM AUTHOR]

Summary: We present a phase‐field fracture model for a stress resultant geometrically exact shell in finite deformation regime where the configuration manifold evolves according to deformation and fracture. The Reissner–Mindlin shell problem is first solved via the finite element method, where the independent unknown fields are the displacement and director. The phase‐field ductile fracture model is then coupled with the verified geometrically exact shell by enriching the three‐field elasto‐plastic free energy with a regularized crack surface energy. To capture the geometrical nonlinearity due to the large plastic deformation exhibited in the processing zone, the corresponding finite‐strain stress resultant elasto‐plasticity model is coupled with the phase field model. This coupling between the stress resultant elasto‐plasticity model and the phase‐field fracture model enables us to predict the different amounts of energy dissipation attributed to plastic deformation and fracture and hence simulate the crack propagation in the ductile regime properly. We introduce a mixed finite element model with displacement, director, and phase‐field order parameters as the nodal degree of freedoms formulated on the mid‐surface. An energy‐based arc‐length method is generalized to track the equilibrium path and mitigate instabilities arising from material nonlinearity. Four numerical examples are presented to validate the implementation of the model and demonstrate its capability to simulate ductile fracture in shell structures. These examples include a plane‐stress tension/shear fracture model, the Muscat‐Fenech and Atkins plate, axial tension of a notched cylindrical shell, and ductile fracture of a simply supported plate under uniform pressure. [ABSTRACT FROM AUTHOR]

Accelerated bridge construction, with innovative connection details and construction technologies, has been extensively investigated and put into practical application for years. Nowadays, there are three commonly used connection methods of accelerated bridge construction technology, namely, lap‐spliced connection, sleeve connection, and socket connection. Due to the convenience of construction and lower requirements of construction accuracy, the socket connection is more suitable for reconstruction and expansion projects of traffic infrastructure, which could minimize the impact on traffic and accelerate construction progress. According to the structural characteristics of the socket connection, there are some design parameters that may significantly affect the seismic resistance of the structure, such as socket embedment length, fabrication of the shear key, and grouting material strength. To fully study the influence of different design parameters on structural performance, an experiment was carried out to investigate the seismic behavior of the precast pier‐footing socket connections with different design parameters. Five 1:2 scale reinforced concrete precast pier‐footing socket connection specimens with different design parameters were designed and tested under cyclically reversed horizontal loads. The development of hysteresis features, failure mode, load‐bearing capacity, stiffness degradation, structural ductility, energy dissipation capacity, and residual drift are analyzed to reveal the influence of the different design parameters on the seismic behavior of the precast pier‐footing socket connection. The seismic behavior of the precast pier‐footing socket connection was significantly influenced by the embedment length especially when the embedment length was less than 1.0bc. When the embedment length was 0.5bc, the failure mode changed from bending damage at the bottom of the precast pier to the anchorage failure of the precast pier‐footing socket connection. When the embedment length was 1.5bc, the fabrication of the shear key had limited improvement on the seismic performance of the specimen, while reducing the ductility of the specimen. When the embedment length was 1.0bc, the grouting material with a strength grade of C60 could be used in the socket connection between the precast pier and footing. The research presented in this paper provides some design suggestions and a technical basis for evaluating the seismic behavior of precast pier‐footing structures with socket connection. [ABSTRACT FROM AUTHOR]

Aim: Novel long‐acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin‐4‐IgG4‐Fc (E4F4) is a long‐acting glucagon‐like peptide‐1 receptor agonist. This first‐in‐human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. Methods: This single‐centre, randomized, double‐blind, placebo‐controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level. Results: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose‐dependent relationship between frequency, severity or causality of treatment‐emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45‐14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose‐dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose‐response relationship in the 1.8‐10.35 mg dose range, with an increased response at the higher doses. Conclusion: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5‐10.35 mg once every 2 weeks. [ABSTRACT FROM AUTHOR]

This work focuses on topology optimization formulations with linear buckling constraints wherein eigenvalues of arbitrary multiplicities can be canonically considered. The non‐differentiability of multiple eigenvalues is addressed by a mean value function which is a symmetric polynomial of the repeated eigenvalues in each cluster. This construction offers accurate control over each cluster of eigenvalues as compared to the aggregation functions such as p$$ p $$‐norm and Kreisselmeier–Steinhauser (K–S) function where only approximate maximum/minimum value is available. This also avoids the two‐loop optimization procedure required by the use of directional derivatives (Seyranian et al. Struct Optim. 1994;8(4):207‐227.). The spurious buckling modes issue is handled by two approaches—one with different interpolations on the initial stiffness and geometric stiffness and another with a pseudo‐mass matrix. Using the pseudo‐mass matrix, two new optimization formulations are proposed for incorporating buckling constraints together with the standard approach employing initial stiffness and geometric stiffness as two ingredients within generalized eigenvalue frameworks. Numerical results show that all three formulations can help to improve the stability of the optimized design. In addition, post‐nonlinear stability analysis on the optimized designs reveals that a higher linear buckling threshold might not lead to a higher nonlinear critical load, especially in cases when the pre‐critical response is nonlinear. [ABSTRACT FROM AUTHOR]

Evidence on the potential causal links of long‐term air pollution exposure with lung cancer incidence (reflected by mortality and hospital admission) was limited, especially based on large cohorts. We examined the relationship between lung cancer and long‐term exposure to particulate matter (PM, including PM2.5, PM10 and PM10‐2.5) and nitrogen dioxide (NO2) among a large cohort of general Chinese adults using causal inference approaches. The study included 575 592 participants who were followed up for an average of 8.2 years. The yearly exposure of PM and NO2 was estimated through satellite‐based random forest approaches and the ordinary kriging method, respectively. Marginal structural Cox models were used to examine hazard ratios (HRs) of mortality and hospital admission due to lung cancer following air pollution exposure, adjusting for potential confounders. The HRs of mortality due to lung cancer were 1.042 (95% confidence interval [CI]: 1.033‐1.052), 1.032 (95% CI:1.024‐1.041) and 1.052 (95% CI:1.041‐1.063) for each 1 μg/m3 increase in PM2.5, PM10 and NO2, respectively. In addition, we observed statistically significant effects of PMs on hospital admission due to lung cancer. The HRs (95%CI) were 1.110 (1.027‐1.201), 1.067 (1.020‐1.115) and 1.079 (1.010‐1.153) for every 1 μg/m3 increase in PM2.5, PM10, PM10‐2.5, respectively. Furthermore, we found larger effect estimates among the elderly and those who exercised more frequently. We provided the most comprehensive evidence of the potential causal links between two outcomes of lung cancer and long‐term air pollution exposure. Relevant policies should be developed, with special attention to protecting the vulnerable groups of the population. [ABSTRACT FROM AUTHOR]

Seismic fragility evaluates the performance of a structure regarding to its capability to withstand earthquake loads by describing the exceedance probability for selected engineering demand parameters. High‐fidelity (HF) models are essential for simulation‐based techniques to obtain accurate fragility assessment in the presence of uncertainties. Dynamic structural behavior however is often difficult to replicate realistically through numerical simulation, especially when parts of the structure are difficult for accurate modeling due to their inherent complex nonlinearity. This study presents the integration of real‐time hybrid simulation (RTHS) with multi‐fidelity Monte Carlo (MFMC) predictor for seismic fragility analysis. RTHS combines physical testing of experimental substructures and numerical modeling of analytical substructures thus presenting a cyber‐physical alternative for HF seismic performance evaluation. The MFMC predictor provides an optimized allocation algorithm that makes full use of data from both HF and low‐fidelity (LF) models to achieve unbiased estimation for response quantities of interests. Experimentally expensive HF data from RTHS is thus integrated with computationally cheap simulation of LF numerical models through MFMC to facilitate seismic fragility analysis. A two‐story steel moment resisting frame (MRF) with self‐centering viscous dampers (SC‐VDs) is utilized to demonstrate the effectiveness and efficiency of the proposed method. Computational simulation is first performed to numerically verify the feasibility of the proposed method for the MRF subjected to non‐stationary stochastic ground motions. RTHS is then conducted experimentally as HF model and integrated with linear elastic LF models through MFMC for fragility analysis of the MRF equipped with SC‐VDs. Both computational and experimental analysis demonstrate that the proposed method provides a promising technique for seismic fragility assessment especially when accurate modeling is not available due to complex structural behavior. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is known as a crucial neurotransmitter synthesized and secreted by dopaminergic neurons and plays a role in regulating human emotions and behaviors. The determination of DA content is of great significance in clinical application and physiological function research. An electroanalytical sensor based on the ternary semiconductor material copper indium selenide (CuInSe2) coated carbon spheres functionalized glassy carbon electrode (CuInSe2@CS/GCE) towards the non‐invasive determination of DA was constructed in this study. The performances of the sensor were characterized using cyclic voltammetry, impedance method, and differential pulse voltammetry. The results show that wrinkled CuInSe2 completely coated on CS. The sensor exhibits good electrochemical kinetics and response signal towards DA, which results from the good electrochemical activity and excellent electroconductibility of transition metal centers of the composite. The determination limit of the proposed sensor towards DA is 0.59 μM (S/N=3), and the linear measuring range is between 1–800 μM. In addition, the sensor exhibits desirable long‐term robustness, reproducibility, repetitiveness, and interference immunity. In the non‐invasive determination towards real samples of human urine and sweat, the sensor provides good recovery rate and small determination deviation. [ABSTRACT FROM AUTHOR]

Background: Benefiting from increased life expectancy and improved perioperative management, more elderly patients with pancreatic head cancer (PHC) underwent pancreaticoduodenectomy (PD). However, individualized predictive models for the safety and efficacy of PD is still lacking. this study aimed to developed three safety‐ and efficacy‐related risk calculators for elderly (> = 65 years) PHC patients. Methods: This study was designed with two research cohorts, namely, the training cohort and the validation cohort, and comprises four general steps: (1) Risk factors were analyzed for the incidence of postoperative complications, cancer‐specific survival (CSS), and overall survival (OS) in the training cohort (N = 271) using logistic and Cox‐regression analysis. (2) Nomograms were then plotted based on the above results. (3) The accuracy of the developed nomogram models was then verified with the validation cohort (N = 134) data using consistency index (C‐index) and calibration curves. (4) We then evaluated the efficacy of these nomograms using decision curve analysis (DCA) in both the training and validation cohorts, and ultimately constructed three online calculators based on these nomograms. Results: We identified ASA, diabetes, smoking, and lymph node invasion as predisposing risk factors for postoperative complications, and the predictive factors that affected both OS and CSS were ASA, diabetes, BMI, CA19‐9 level, and tumor diameter. By integrating the above risk factors, we constructed three nomograms on postoperative complication, CSS, and OS. The C‐index for complication, CSS, and OS were 0.824, 0.784, and 0.801 in the training cohort and 0.746, 0.718, and 0.708 in the validation cohort. Moreover, the validation curves and DCA demonstrated good calibration and robust compliance in both training and validation cohorts. We then developed three web calculators (https://caiming.shinyapps.io/CMCD/, https://caiming.shinyapps.io/CMCSS/, and https://caiming.shinyapps.io/CMOS/) to facilitate the use of the nomograms. Conclusions: The calculators demonstrated promising performance as an tool for predicting the safety and efficacy of PD in elderly PHC patients. [ABSTRACT FROM AUTHOR]

Shake tables are useful instruments for investigating structural seismic responses, while they may introduce excessive vibrations on surrounding environments during operation. This study investigates the impact of vibration generated by a 6 m×9 m large shake table on the shake table laboratory and the surrounding buildings. To begin, vibration sensors were strategically installed throughout the shake table laboratory and the surrounding buildings to investigate their vibration characteristics during operations of the shake table. Subsequently, the vibration comfort of the shake table laboratory and the surrounding buildings was thoroughly evaluated. Finally, the overall finite element model of the ground‐shake table laboratory‐surrounding buildings was established by simulating the infinite soil with a viscoelastic boundary, and the parametric study of the vibration isolation trench was conducted. This study is the first to accurately, objectively, and quantitatively investigate the impact of large shake table operation on the surrounding environment. The results presented will be useful for the laboratory managers to develop reasonable loading schemes, as well as to optimize the design of other similar laboratories and vibration isolation measures. [ABSTRACT FROM AUTHOR]

The catalytic performance of metal–organic frameworks (MOFs) in Li‐S batteries is significantly hindered by unsuitable pore size, low conductivity, and large steric contact hindrance between the catalytic site and lithium polysulfide (LPSs). Herein, the smallest π‐conjugated hexaaminobenzene (HAB) as linker and Ni(II) ions as skeletal node are in situ assembled into high crystallinity Ni‐HAB 2D conductive MOFs with dense Ni‐N4 units via dsp2 hybridization on the surface of carbon nanotube (CNT), fabricating Ni‐HAB@CNT as separator modified layer in Li‐S batteries. As‐obtained unique π‐d conjugated Ni‐HAB nanostructure features ordered micropores with suitable pore size (≈8 Å) induced by HAB ligands, which can cooperate with dense Ni‐N4 chemisorption sites to effectively suppress the shuttle effect. Meanwhile, the conversion kinetics of LPSs is significantly accelerated owing to the small steric contact hindrance and increased delocalized electron density endued by the planar tetracoordinate structure. Consequently, the Li‐S battery with Ni‐HAB@CNT modified separator achieves an areal capacity of 6.29 mAh cm−2 at high sulfur loading of 6.5 mg cm−2 under electrolyte/sulfur ratio of 5 µL mg−1. Moreover, Li‐S single‐electrode pouch cells with modified separators deliver a high reversible capacity of 791 mAh g−1 after 50 cycles at 0.1 C with electrolyte/sulfur ratio of 6 µL mg−1. [ABSTRACT FROM AUTHOR]

Objective: Clinical practitioners face a significant challenge in maintaining a healthy balance between overtreatment and missed diagnosis in the management of intraductal papillary mucinous neoplasm (IPMN). The current study aimed to identify significant risk factors of malignant IPMN from a series of clinical and radiological parameters that are widely available and noninvasive and develop a method to individually predict the risk of malignant IPMN to improve its management. Methods: We retrospectively investigated 168 patients who were pathologically diagnosed with IPMN after individualized pancreatic resection between June, 2012 and December, 2020. Independent predictors determined using both univariate and multivariate analyses to construct a predictive model. The discriminatory power of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC). Decision curve analysis was performed to demonstrate the clinical usefulness of the nomogram. Internal cross validation was performed to assess the validity of the predictive model. Results: In the multivariate analysis, five significant independent risk factors were identified: increased serum CA19‐9 level, low prognostic nutritional index (PNI), cyst size, enhancing mural nodule, and main pancreatic duct diameter. The nomogram based on the parameters mentioned above had outstanding performance in distinguishing malignancy, with an AUC of 0.907 (95% confidence interval: 0.859–0.956, p < 0.05), which remained 0.875 after internal cross‐validation, and showed good clinical usefulness. Conclusion: A novel nomogram for predicting malignant IPMN first introducing PNI was developed, which may aid in improving IPMN management. Nevertheless, external validation is required to confirm its efficacy. With the hope of improving the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, we developed a new malignancy‐predicted nomogram for IPMN, based on five verified independent predictors of malignant IPMN in our study. We employed Prognostic nutrition index (PNI) to constructed the nomogram for the first time and stratified the diameter of main pancreatic duct and the size of Mural Nodules which were helpful to achieve a more precise risk for malignancy. The nomogram shows excellent capability in predicting malignant IPMN and has a promising application potential. [ABSTRACT FROM AUTHOR]

Site‐structure cluster interaction (SSCI) has a significant effect on the seismic response of densely distributed buildings, and rationally and effectively quantifying its effect when modelling the urban seismic damage can provide more optimal decisions to mitigate earthquake disasters. This paper focuses on the input motion of the structures, by extracting the main influential parameters of SSCI and adopting the loosely typed wavelet packet neural network to rapidly simulate the spatially varying ground motion in the urban environment. In the proposed framework, the wavelet packet energy ratio is presented to describe the variation of ground motion characteristics and used as the sole output to carry out the multi‐resolution spectral modulation, and the training samples were accumulated by a validated finite element simulation method. The developed surrogate model considers the effects of a series of factors, including the earthquake intensity, site condition, configuration of structure cluster, structural dynamic characteristics and spacing, and is superior to the one using conventional artificial neural network. It is verified by a virtual test that the waveshape and spectral features of the predicted ground motion agree well with the target result with an error of peak acceleration being only 1.23%. The suggested approach has the advantages of better modulation precision and lower sample size requirement. Moreover, it is almost zero cost to use the developed surrogate model to correct the ground motion of urban buildings and to consider the influence of SSCI, and the structural seismic response can be more factually displayed in the time and space domains. These specialties make it a promising technique in the rapid assessment of urban seismic damage. [ABSTRACT FROM AUTHOR]

Aqueous sodium‐ion batteries (ASIB) offer many potential applications in large‐scale power grids since they are inexpensive, safe, and environmentally friendly. Sodium superionic conductors (NASICON), especially carbon‐coated Na3V2(PO4)3 (NVP), have attracted much attention due to the full use of their high ion migration speed. However, the poor cycle lifespan and capacity retention of NVP hinder its application in ASIB. Herein, a novel bimetal‐doped Na3V1.3Fe0.5W0.2(PO4)3 (NV1.3Fe0.5W0.2P) cathode is designed and synthesized to achieve outstanding cycling stability (95 % of initial capacity at 50th cycle). The electrochemical behavior and charge storage mechanism of NV1.3Fe0.5W0.2P are systematically investigated by various in situ and ex situ characterizations. The Fe and W codoping could stabilize the NASICON framework to suppress the proton attack on the Na site in the aqueous electrolyte, thus resulting in excellent cycling stability. DFT calculations show that bimetallic doping increases the structural stability of NVP. Moreover, an ASIB fabricated using a NV1.3Fe0.5W0.2P cathode and a NaTi2(PO4)3 anode delivers 64 mAh g−1 at room temperature, 95 % capacity retention after 50 cycles (1 A g−1). [ABSTRACT FROM AUTHOR]

The objective of this paper is to provide a discrete PID controller design procedure for maximizing stability margins. First, a new and complete characterization of the entire set of stabilizing discrete PID controllers for a given plant is presented. Then, based on this characterization, an efficient algorithm is developed for testing if, for a given plant, there exists a digital PID controller gain parameter space corresponding to closed‐loop poles being inside the circle of radius ρ centered at the origin. The developed algorithm is finally applied along with a bisection strategy to determine, for a specified small positive number ε, a minimum value ρε* and the corresponding ρε*−stabilizing discrete PID controller set for achieving at least 1−ρε* of stability margin. To illustrate the features of our new characterization of stabilizing digital PID controller sets and the effectiveness of the presented algorithms to the maximum stability‐margin discrete PID controller design, two numerical examples are provided. [ABSTRACT FROM AUTHOR]

Fundamentally understanding the structure–property relationship is critical to design advanced electrocatalysts for lithium‐sulfur (Li−S) batteries, which remains a formidable challenge. Herein, by manipulating the regulable cations in spinel oxides, their geometrical‐site‐dependent catalytic activity for sulfur redox is investigated. Experimental and theoretical analyses validate that the modulation essence of cooperative catalysis of lithium polysulfides (LiPSs) is dominated by LiPSs adsorption competition between Co3+ tetrahedral (Td) and Mn3+ octahedral (Oh) sites on Mn3+Oh−O−Co3+Td backbones. Specifically, high‐spin Co3+Td with stronger Co−S covalency anchors LiPSs persistently, while electron delocalized Mn3+Oh with adsorptive orbital (dz2) functions better in catalyzing specialized LiPSs conversion. This work inaugurates a universal strategy for sculpting geometrical configuration to achieve charge, spin, and orbital topological regulation in electrocatalysts for Li−S batteries. [ABSTRACT FROM AUTHOR]

Insects employ various types of gustatory receptors (GRs) to identify nutrient‐rich food and avoid toxic substances. The larval gustatory system is the critical checkpoint for food acceptance or rejection. As a specialist herbivore, the larvae of Bactrocera minax feed only on unripe citrus fruits. However, how larvae use GRs to check and adapt to the secondary metabolites in unripe citrus fruits remains unknown. In this study, we first performed developmental expression profiles showing that most BminGRs genes were highly expressed in 1st and 2nd instar larvae and that tissue‐specific expression indicated high expression of most BminGRs genes in the mouthparts of 2nd instar larvae. Furthermore, we found that silencing BminGR59f by RNA interference (RNAi) affected the growth of 2nd instar B. minax larvae. Hesperidin and naringin were screened as ligands of BminGR59f via RNAi and cell calcium imaging, and the combination of these two flavones increased the body weight of larvae. In summary, we identified a novel gustatory perception pattern in B. minax for detecting hesperidin and naringin, which boosted the growth of B. minax larvae. These results shed light on how specialist herbivores detect and adapt to host metabolites in adverse environments depending on larval GRs. [ABSTRACT FROM AUTHOR]

Stability of real time hybrid simulation (RTHS) has attracted considerable attention since actuator delay would deviate experiment results or even destabilize the real‐time test. Previous studies have extensively investigated stability of RTHS for linear systems, while stability of RTHS for nonlinear system remains unclear. This study introduces the Takagi‐Sugeno (T‐S) method to describe the nonlinear behavior in a piecewise linear way, then investigates the stability of nonlinear system with time delay through the Lyapunov‐Krasovskii (L‐K) theory. Such approach successfully solves the stability problem of RTHS with coupled bilinear‐hysteresis substructure and actuator delay, and proposes a stability criterion in the form of linear matrix inequality (LMI). It proves that the stability of RTHS is determined by the most unfavorable state of nonlinear system. In the SDOF case with stiffness softening, the initial elastic state is the most unfavorable; while for the MDOF case with multiple delays, the stability is determined by the overlap part of stable region of each nonlinear state. The computational simulation and experimental results show that the difference between linear‐ and nonlinear hysteretic system with time delay is that when instability occurs, latter could remain energy balanced since the time‐delay energy is dissipated by hysteresis behavior, while energy accumulates in the former leading to unbounded responses. The proposed approach provides a potential tool for experimental design of RTHS before the test, the time‐delay control during the test and error evaluation after the test. [ABSTRACT FROM AUTHOR]

Soil‐structure cluster dynamic interaction (SSCI) has a significant effect on structural responses as well as ground motions for soft soil, while investigations on the latter remain limited. In this paper, four test models, including the free field model, soil‐single structure model, soil‐equal height structure cluster model, and soil‐multiple height structure cluster model, were manufactured and investigated through large scale shaking table tests. The effect of structure numbers, layouts, structural dynamic characteristics and seismic spectrum characteristics on the ground motions was discussed. On this basis, finite element analysis and wavelet packet decomposition were employed to further investigate the evolution rule of cluster effect. The results manifested that, due to the structure cluster, the predominant period of the original free field could be elongated notably and earthquake response spectrum in the long period domain was amplified, especially under the excitation of seismic waves with abundant low‐frequency components. The influence of SSCI on ground motions is chiefly reflected in the variation of site predominant period and the soil damping during the vibration. In addition, the cluster effect on ground motion presents a monotonous degressive trend with the increase of the structural spacing, and its attenuation rate is negatively correlated with structural height, while the difference in ground motion due to different structure numbers becomes insignificant with the increase of structural spacing. [ABSTRACT FROM AUTHOR]

We have quantitatively investigated the precipitation of DNA in different valence cations and in various ethanol concentration solution. In free ethanol condition, monovalent ion cannot induce DNA condensation and in turn to precipitation. Divalent ion can cause DNA precipitation as the concentrations of both Mg2+ (MgCl2) and Ca2+ (CaCl2) go up to a critical value of about 50 mM. After adding ethanol, monovalent ion and divalent ion can promote DNA precipitation significantly, but it has no effect on the process by trivalent ions. In monovalent ion solution of 100 mM, the critical volume ratio of ethanol is about 52% for DNA precipitation. However, the value decreases significantly to 4% in 25 mM divalent ion solution. Based on the precipitation curves, we quantitatively calculated the binding energies between the cations and phosphate group of DNA. For monovalent ions and in aqueous solution, the Na+‐DNA binding energy is about −5.52 KJ·Mol−1 (−2.63 kBT, the precipitation temperature is 253 Kelvin) and the K+‐DNA binding energy is about −4.77 KJ·Mol−1 (−2.27 kBT). For divalent ions and in the same condition, the Ca2+‐DNA binding energy is about −8.25 KJ·Mol−1 (−3.93 kBT) and the Mg2+‐DNA binding energy is about −8.67 KJ·Mol−1 (−4.13 kBT). The scenario of DNA precipitation modulation by ethanol and zwitterionic ions is demonstrated by atomic force microscopy (AFM) imaging intuitively. [ABSTRACT FROM AUTHOR]

The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin‐induced diabetic rats, glyoxal‐treated R28 cells and hypoxia‐treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba‐1, TSPO, NF‐κB, Nrf2 and inflammation‐related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal‐treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia‐treated microglia, which was largely dampened by FKN. The NF‐κB and Nrf2 expressions and intracellular ROS were up‐regulated in hypoxia‐treated microglia compared with that in normoxia control, and FKN significantly inhibited NF‐κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF‐κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation‐related cytokines and ROS, and protect the retina from diabetes insult. [ABSTRACT FROM AUTHOR]

Background: We have limited information about neuroendocrine carcinoma (NEC) of the gallbladder. The purpose of this paper is to compare clinical and pathological features between different age groups and prognostic factors for gallbladder NEC and how it differs from adenocarcinoma (ADC) of the gallbladder. Patients and methods: This study included 28 gallbladder NEC patients and 137 ADC patients whose clinical characteristics and pathological findings were retrospectively collected. Propensity score matching and Cox regression analysis were used for the analysis of prognostic factors. Results: We divided NEC patients into two groups based on the age more than or less than 60 years. Most of the NEC patients less than 60 years old complained of abdominal pain or discomfort (p = 0.038), and more younger patients accepted adjuvant therapy (p = 0.020) than older patients did. CD56 was positive in all patients more than 60 years old, which is significantly higher than that of younger patients (p = 0.039). The mean age was similar between NEC and ADC patients. After eliminating confounding factors between NEC and ADC patients, the overall survival rates were still lower in NEC patients. Univariate analysis extracted six possible risk factors. Multivariate analysis indicated that surgery type, tumor size, and existence of gallstones were independent prognostic factors. Conclusion: The overall survival of gallbladder NEC is not associated with age. In this study, surgical method and tumor size were found to be independent risk factors for NECs. In addition, NEC patients have a worse prognosis than ADC patients with similar clinical and pathological features. [ABSTRACT FROM AUTHOR]

Studies have shown that the change in lumbar spine bone mineral density with different osteoporosis drugs had a beneficial effect on the frequency of new vertebral and nonvertebral fractures in postmenopausal females, but their results were conflicting. This meta‐analysis was performed to evaluate this relationship. A systematic literature search up to May 2020 was performed and 20 studies with 73,390 postmenopausal females were included; of them, a total of 41,980 were treated with osteoporosis drugs and 31,410 with placebo. They reported relationships between the change in lumbar spine bone mineral density and the frequency of new vertebral and nonvertebral fractures in postmenopausal females. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated comparing the osteoporosis drugs to placebo effect on the frequency of new vertebral and nonvertebral fractures in postmenopausal females using the dichotomous method with a random or fixed‐effect model. Treatment with osteoporosis drugs had significantly lower frequency of new vertebral fractures (OR, 0.53; 95% CI, 0.45–0.63, P < 0.001) and nonvertebral fractures (OR, 0.82; 95% CI, 0.78–0.87, P < 0.001) compared to placebo in postmenopausal females. Treatment with osteoporosis drugs had a significantly lower frequency of new vertebral and nonvertebral fractures compared to placebo in postmenopausal females. This relationship forces us to recommend osteoporosis drugs in postmenopausal females to avoid any possible new fractures. A cost‐effective study is recommended. [ABSTRACT FROM AUTHOR]

Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8‐week‐old diabetic rat retinas. It is widely acknowledged that microglia‐mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro‐inflammatory factors such as cyclooxygenase‐2 (COX‐2), interleukin‐1β (IL‐1β), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia‐treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Deep mining of the molecular mechanisms underlying diabetic retinopathy (DR) is critical for the development of novel therapeutic targets. This study aimed to identify key molecular signatures involved in experimental DR on the basis of integrated bioinformatics analysis. Four datasets consisting of 37 retinal samples were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus. After batch‐effect adjustment, bioinformatics tools such as Networkanalyst, Enrichr, STRING, and Metascape were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein–protein interaction networks. The hub genes were identified using Cytoscape software. The DEGs of interest from the meta‐analysis were confirmed by quantitative reverse transcription‐polymerase chain reaction in diabetic rats and a high‐glucose‐treated retinal cell model, respectively. A total of 743 DEGs related to lens differentiation, insulin resistance, and high‐density lipoprotein (HDL) cholesterol metabolism were obtained using the meta‐analysis. Alterations of dynamic gene expression in the chloride ion channel, retinol metabolism, and fatty acid metabolism were involved in the course of DR in rats. Importantly, H3K27m3 modifications regulated the expression of most DEGs at the early stage of DR. Using an integrated bioinformatics approach, novel molecular signatures were obtained for different stages of DR progression, and the findings may represent distinct therapeutic strategies for DR patients. [ABSTRACT FROM AUTHOR]

Developing cost‐effective and high‐performance catalysts for oxygen evolution reaction (OER) is essential to improve the efficiency of electrochemical conversion devices. Unfortunately, current studies greatly depend on empirical exploration and ignore the inherent relationship between electronic structure and catalytic activity, which impedes the rational design of high‐efficiency OER catalysts. Herein, a series of bimetallic Ni‐based metal‐organic frameworks (Ni‐M‐MOFs, M = Fe, Co, Cu, Mn, and Zn) with well‐defined morphology and active sites are selected as the ideal platform to explore the electronic‐structure/catalytic‐activity relationship. By integrating density‐functional theory calculations and experimental measurements, a volcano‐shaped relationship between electronic properties (d‐band center and eg filling) and OER activity is demonstrated, in which the NiFe‐MOF with the optimized energy level and electronic structure situated closer to the volcano summit. It delivers ultra‐low overpotentials of 215 and 297 mV for 10 and 500 mA cm−2, respectively. The identified electronic‐structure/catalytic activity relationship is found to be universal for other Ni‐based MOF catalysts (e.g., Ni‐M‐BDC‐NH2, Ni‐M‐BTC, Ni‐M‐NDC, Ni‐M‐DOBDC, and Ni‐M‐PYDC). This work widens the applicability of d band center and eg filling descriptors to activity prediction of MOF‐based electrocatalysts, providing an insightful perspective to design highly efficient OER catalysts. [ABSTRACT FROM AUTHOR]

The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti‐inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood–retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF‐α, IL‐1β, ICAM‐1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO‐1, occludin, JAM‐A, and claudin‐5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF‐κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF‐κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin‐based DR therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyse 69 Chinese patients with USH2A mutations and to assess the genotype–phenotype correlation. Methods: All 36 Usher syndrome type IIA patients and 33 nonsyndromic RP (retinitis pigmentosa) patients underwent clinical examinations. Eye examinations included best‐corrected visual acuity, slit‐lamp biomicroscopy, fundus examination with dilated pupils, fundus fluorescent angiography, visual field test, full‐field electroretinography and optic coherence tomography; audiological assessment included pure tone audiometry and hearing thresholds. The molecular diagnosis of genotype combined the single‐gene Sanger sequencing and next‐generation sequencing. This study is a retrospective study. Results: The mean age of first symptoms with Usher syndrome type IIa and nonsyndromic RP patients was 13.7 versus 29.8 years (ocular phenotypes, p < 0.001); 17.7 versus 29.9 years (nyctalopia, p < 0.001); 44.7 versus 54.8 years (low vision based on VF, p < 0.001); 41.7 versus 54.7 years (low vision based on VA, p < 0.001); and 46.0 versus 56.7 years (legal blindness based on VF, p < 0.001). There was significant difference in variants in the two groups (p < 0.05). Among patients with mutation c.2802T > G (p.Cys934Trp), more (66.7%) presented with normal hearing. All patients (3/3, 100%) with the variant c.8232G > C (p.Trp2744Cys) had hearing loss. Furthermore, we identified 23 novel variants in USH2A. Conclusions: Patients with Usher syndrome type IIa had an earlier onset of the disease, inferior visual function and presented with more truncating variants, compared with the nonsyndromic RP patients. [ABSTRACT FROM AUTHOR]

Summary: Based on phase‐field theory, we develop a simple and robust single relaxation time (SRT) lattice Boltzmann (LB) model for simulating complex multiphase flows with large density ratios (up to 2000). The approach utilizes two LB equations (LBE), one is used to describe the interface behavior and the other is used to calculate the hydrodynamic properties. To improve the accuracy and stability in capturing interface, the high‐order LB model derived through the fourth‐order Chapman‐Enskog expansion analysis is applied to Cahn‐Hilliard equation. For solution of the flow field, a modified particle distribution function in the pressure‐velocity formulation is constructed to correctly consider the effect of local density variation and continuous pressure field. With such improvement, the proposed multiphase LB model is able to maintain numerical stability for the problem with very large density ratio, lower relaxation parameter and complex interface. For validation, a series of benchmark cases are carried out. Specially, the full potential of the proposed model is validated by bubble bursting at a free surface, bubble rising and droplet splashing with a density ratio of 2000. In all test cases, the obtained numerical results agree well with the reference data or the analytical solutions. [ABSTRACT FROM AUTHOR]

In‐service bridge wires often fail prior to the design life subjected to alternating stresses and environmental erosion. In this paper, a novel corrosion fatigue test device, integrating fatigue testing machine and electrochemical accelerated corrosion assemblies, was developed to characterize the corrosion fatigue and electrochemical behaviour of the wires. Using the developed device, corrosion fatigue tests of corroded bridge wires under different corrosion and loading conditions were conducted. Electrochemical characteristics, corrosion fatigue behaviour, failure mechanism, and so forth were investigated according to electrochemical measurements, fracture morphologies and the lifetime of wires. Results evidence the synchronization of corrosion and fatigue and show the accelerated corrosion due to static and fatigue stresses. Additionally, cracking and fracture induced by multiple crack initiation was dominant in corrosion fatigue of corroded wires, and the coexistence of multiple corrosion pits decreased the lifetime significantly. [ABSTRACT FROM AUTHOR]

Purpose: To explore the mechanisms of erythropoietin (EPO) in maintaining outer blood‐retinal barrier (BRB) in diabetic rats. Methods: Sprague‐Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin, and then followed by intravitreal injection of EPO. Two and four weeks later, the permeability of outer BRB was examined with FITC‐dextran leakage assay, following a method to demarcate the inner and outer retina based on retinal blood supply. The glyoxal‐treated ARPE‐19 cells, incubated with EPO, soluble EPO receptor (sEPOR), Gö6976, or digoxin, were studied for cell viability and barrier function. The expressions of ZO‐1, occludin, VEGFR2, HIF‐1α, MAPKs, and AKT were examined with Western blot and immunofluorescence. Results: The major Leakage of FITC‐dextran was detected in the outer nuclear layer in both 2‐ and 4‐week diabetic rats. The leakage was largely ameliorated in EPO‐treated diabetic rats. The protein expressions of ZO‐1 and occludin in the RPE‐Bruch's membrane choriocapillaris complex were significantly decreased, whereas HIF‐1α and JNK pathways were activated, in 4‐week diabetic rats. These changes were prevented by EPO treatment. The in vitro study with ARPE‐19 cells confirmed these changes, and the protective effect of EPO was abolished by sEPOR. Gö6976 and digoxin rescued the tight junction and barrier function in glyoxal‐treated ARPE‐19 cells. Conclusions: In early diabetic rats, the outer BRB might be more severely damaged and its breakdown is the major factor for retinal oedema. EPO maintains the outer BRB integrity through down‐regulation of HIF‐1α and JNK signallings, and thus up‐regulating ZO‐1 and occludin expressions in RPE cells. [ABSTRACT FROM AUTHOR]

A novel flame‐retardant hsaltryptamine phosphaphenanthrene (HTD) was successfully synthesized and characterized by Fourier transform infrared spectrometry and nuclear magnetic resonance. HTD was used to improve flame retardancy of epoxy resin (EP). When the addition content of HTD reached 4 wt%, the EP/HTD thermoset passed a UL‐94 V‐1 rating and had limited oxygen index value of 29.2%. Compared to neat EP, the release of heat and smoke decreased significantly due to the gaseous‐phase and condensed‐phase flame‐retardant mechanism of HTD. The char residue after cone calorimeter test was analyzed and the results showed that the char residue of EP/8%HTD thermoset exhibited homogeneously crosslinked char layer, which acted as a good barrier for the release of heat and oxygen. The transmittance and mechanical properties of EP/HTD thermosets had been tested. EP/HTD thermoset possessed high transparency and good mechanical properties. In comparison to neat EP, tensile strength, flexural strength, and Izod unnotched impact strength of EP with 8% loading of HTD was improved by 21.9%, 20.5%, and 17.4%, respectively. POLYM. ENG. SCI., 59:2008–2015, 2019. © 2019 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Recently, Chinese medical education has exhibited a shifting trend from teacher‐centered instruction to student‐centered learning, which usually includes a self‐directed learning process. Providing students with high‐quality and appropriate supplemental resources is necessary for their self‐directed learning. This study aimed to investigate the appropriateness of AccessMedicine, an online medical resource, for first‐year medical students at Tongji University in China. In the randomized controlled trial, 42 students were stratified by gender and grade point average (GPA) and randomly assigned to either the control group or AccessMedicine group. The students' learning outcomes were assessed with quizzes, including tests before and after learning and a final examination. Paired t‐tests and two‐way analysis of variance were performed for statistical analysis. We found that AccessMedicine‐assisted learning improved student performance on tests and decreased the overall failure rate in the final examination. Further analysis showed that the final examination score of the subgroup with high GPAs in the AccessMedicine group significantly increased, but not that of the subgroup with low GPAs, indicating that AccessMedicine‐assisted learning was more beneficial for good students than for poor students. A survey showed that professional vocabularies were the greatest obstacles to learning with AccessMedicine. Moreover, English language skills greatly affected the students' learning outcomes for the English resource but not those for the Chinese resource. Taken together, our results demonstrated that AccessMedicine was appropriate for Chinese medical education and improved the learning outcomes of students, especially students with high GPAs and a good command over the English language. © 2019 International Union of Biochemistry and Molecular Biology, 47(3):272–278, 2019. [ABSTRACT FROM AUTHOR]

Abstract: Liquid metals (LMs) have attracted great attentions in electronics for great interface contact and flowability. Here, an LM‐gated tribotronic transistor (LMTT) is demonstrated, in which an electrostatic potential is created through the triboelectrification of LM and dielectric layer, and the carrier transport between drain and source can be tuned by the swing‐induced electrostatic potential instead of the traditional gate voltage. Based on the fabricated LMTTs, an electronic gradienter is developed, which can be used for angle measurement and exhibits a great sensitivity, large sensing range, and excellent stability. This work has first introduced the LM into the tribotronic device, which may have potential applications in mechanical calibration, civil engineering, and geologic exploration. [ABSTRACT FROM AUTHOR]

Abstract: Growing demand in automobile safety system raises a requirement to electronic devices being self‐powered, stable, and durable. Herein, a self‐powered Hall vehicle sensor (SPHVS) is demonstrated for automobile safety system, which integrates the triboelectric nanogenerator, the management circuit, the magnet, and the Hall element. The tribotronic constant current source is proposed to steadily power the Hall element in rotational motion at any different speeds. Furthermore, the performances of the SPHVS for vehicle speed sensing and vehicle braking monitoring are systematically investigated, which exhibits wide sensing range, great stability, and excellent sensitivity. This work clearly proposes a promising solution for speed sensing and braking monitoring, and indicates the potential applications of power tribotronics for the self‐powered electronic devices in prospective automobile industry. [ABSTRACT FROM AUTHOR]

ABSTRACT: Macrophages play critical roles in wound healing process. They switch from “classically activated” (M1) phenotype in the early inflammatory phase to “alternatively activated” (M2) phenotype in the later healing phase. However, the dynamic process of macrophage phenotype switching in diabetic wounds burdened with bacteria is unclear. In this report, Pseudomonas aeruginosa, frequently detected in diabetic foot ulcers, was inoculated into cutaneous wounds of db/db diabetic mice to mimic bacterium‐infected diabetic wound healing. We observed that P. aeruginosa infection impaired diabetic wound healing and quickly promoted the expression of pro‐inflammatory genes (M1 macrophage markers) tumor necrosis factor‐α (tnf‐α), interleukin‐1β (il‐1β) and il‐6 in wounds. The expression of markers of M2 macrophages, including il‐10, arginase‐1, and ym1 were also upregulated. In addition, similar gene expression patterns were observed in macrophages isolated directly from wounds. Immunostaining showed that P. aeruginosa infection increased both the ratios of M1 and M2 macrophages in wounds compared with that in control groups, which was further confirmed by in vitro culturing macrophages with P. aeruginosa and skin fibroblast conditioned medium. However, the ratios of the expression levels of pro‐inflammatory genes to anti‐inflammatory gene il‐10 was increased markedly in P. aeruginosa infected wounds and macrophages compared with that in control groups, and P. aeruginosa prolonged the presence of M1 macrophages in the wounds. These data demonstrated that P. aeruginosa in diabetic wounds activates a mixed M1/M2 macrophage phenotype with an excessive activation of M1 phenotype or relatively inadequate activation of M2 phenotype. [ABSTRACT FROM AUTHOR]

Abstract: Stem cells are cells that can self‐renew and differentiate into a variety of cell types under certain conditions. Stem cells have great potential in regenerative medicine and cell therapy for the treatment of certain diseases. To deliver knowledge about this frontier in science and technology to medical undergraduate students, we designed an innovative practical experiment for freshmen in their second semester. The lab exercise focused on rat bone marrow mesenchymal stem cell (BMSC) isolation, cell culture and differentiation, and it aimed to help students master the aseptic techniques for cell culture, the basic methods and procedures for the primary culture and passage of BMSCs, the basic procedure for the directional differentiation of BMSCs into adipocytes and their subsequent identification by oil‐red‐O staining. This lab exercise is a very meaningful and useful introduction to stem cell collection and manipulation and inspires medical students to deepen their understanding of translational medicine and regenerative medicine. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):151–154, 2018. [ABSTRACT FROM AUTHOR]

Biochemistry and cellular biology courses for medical students at Tongji University include the assessment that provides students with feedback to enhance their learning, which is a type of formative assessment. However, frequent instant feedback and guidance for students is often absent or inconsistently included in the teaching process. WeChat, the most popular Chinese social media, was introduced in biochemistry and cellular biology course. A WeChat official account (OA) was set up as an instant interactive platform. Over a period of two semesters, OA sent 73 push notifications. The components included course notices, preclass thought questions, after-class study materials, answer questions and feedback, simulation exercises, teacher-student interaction, and research progress relevant to the course. WeChat OA served as an active-learning teaching tool, provided more frequent feedback and guidance to students, and facilitated better student-centered communication in the teaching process. Using the WeChat OA in medical teaching emphasized interactive, interoperable, effective, engaging, adaptable, and more participatory teaching styles. As a new platform, WeChat OA was free, Internet-reliant, and easily managed. Using this new medium as a communication tool accelerated further advancement of instant feedback and improvement in teaching activities. Notifications and interactive feedback via the mobile social medium WeChat OA anytime and anywhere facilitated a student-centered teaching mode. Use of WeChat OA significantly increased the proportion of students interactively participating and resulted in a high degree of student satisfaction. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):421-425, 2017. [ABSTRACT FROM AUTHOR]

The dry (nonneovascular) form of age-related macular degeneration ( AMD), a leading cause of blindness in the elderly, has few, if any, treatment options at present. It is characterized by early accumulation of cellular waste products in the retinal pigmented epithelium ( RPE); rejuvenating impaired lysosome function in RPE is a well-justified target for treatment. It is now clear that amino acids and vacuolar-type H+- ATPase (V- ATPase) regulate the mechanistic target of rapamycin, complex 1 ( mTORC1) signaling in lysosomes. Here, we provide evidence for the first time that the amino acid transporter SLC36A4/proton-dependent amino acid transporter ( PAT4) regulates the amino acid pool in the lysosomes of RPE. In Cryba1 (gene encoding βA3/A1-crystallin) KO (knockout) mice, where PAT4 and amino acid levels are increased in the RPE, the transcription factors EB ( TFEB) and E3 ( TFE3) are retained in the cytoplasm, even after 24 h of fasting. Consequently, genes in the coordinated lysosomal expression and regulation ( CLEAR) network are not activated, and lysosomal function remains low. As these mice age, expression of RPE65 and lecithin retinol acyltransferase ( LRAT), two vital visual cycle proteins, decreases in the RPE. A defective visual cycle would possibly slow down the regeneration of new photoreceptor outer segments ( POS). Further, photoreceptor degeneration also becomes obvious during aging, reminiscent of human dry AMD disease. Electron microscopy shows basal laminar deposits in Bruch's membrane, a hallmark of development of AMD. For dry AMD patients, targeting PAT4/V- ATPase in the lysosomes of RPE cells may be an effective means of preventing or delaying disease progression. [ABSTRACT FROM AUTHOR]

Background: Dysfunctions in the autophagy and endolysosomal pathways have been reported in Alzheimer's Disease and related tauopathies. The presence of disease‐associated tau itself may play a role in damaging these pathways leading to its altered clearance. Minimal expression of a disease‐associated truncated tau species (Tau35) in mice results in a progressive tauopathy phenotype, including increased tau phosphorylation, cognitive and behavioural abnormalities and impaired protein clearance. In this study, we sought to explore the effects of Tau35 on the autophagy and endolysosomal pathway in cultured cells expressing Tau35 and from Tau35 mice. Method: Chinese hamster ovary (CHO) cells stably expressing Tau35 (CHO‐Tau35) or full‐length human 2N4R tau (CHO‐FL) were generated. Primary cortical neurons from Tau35 transgenic and wild‐type mice were isolated and cultured for 14 days in vitro (DIV). Cells were fixed for immunocytochemistry or lysed to isolate protein/RNA for western blotting and RT‐qPCR to detect the effect of Tau35 expression on autophagy and lysosomal‐related proteins and genes. Result: CHO‐Tau35 cells exhibited a marked reduction in several autophagy and lysosomal‐related markers, including LC3‐II, LAMP2 and cathepsin D. CHO‐Tau35 cells also accumulated lipid droplets and showed disruptions in mammalian target of rapamycin complex 1 (mTORC1) activity and autophagic flux. Moreover, Tau35 expression also resulted in alterations in early endocytic markers, including EEA1. Similar reductions in autophagic and endosomal markers were observed in primary cortical neurons cultured from Tau35 mice. Notably, the nuclear translocation of transcription factor EB (TFEB), a key mediator of lysosomal biogenesis, as well as the transcription of several TFEB‐target genes, was significantly reduced in both CHO‐FL and CHO‐Tau35 cells. Conclusion: Our findings suggest that disease‐associated truncated tau damages the clearance of cellular proteins and reduces TFEB‐mediated lysosomal biogenesis. Investigating whether autophagy is disrupted due to tau‐induced lysosomal dysfunction may lead to the identification of novel therapeutic targets for dementia. [ABSTRACT FROM AUTHOR]

ABSTRACT A reconfigurable microstrip antenna with frequency and radiation pattern selectivity is presented. The proposed planar antenna consists of six symmetrical main radiating elements and 12 parasitic elements. By controlling the states of PIN diodes, the proposed antenna is capable of operating within 2.29-2.50 GHz, 2.48-2.69 GHz, and 2.77-2.91 GHz, respectively, and steering radiation patterns in the whole azimuth plane to six different directions. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:2848-2854, 2015 [ABSTRACT FROM AUTHOR]

SUMMARY The self-centering prestressed concrete (SCPC) moment resisting frame (MRF) with web friction devices (WFDs) is a new type of structure that integrates advantages of post-tensioned precast concrete MRFs and self-centering steel MRFs. In this paper, the configuration of the connection and design guidelines are presented. To further reduce damage to the connection under cyclic loading and facilitate implementation in practice, several significant improvements are proposed and experimentally validated in this study, including the following: (i) the welded connection is replaced by the bolted connection; (ii) aluminum plates are used for friction instead of brass plates to reduce the material costs without decreasing the energy dissipation capacity; and (iii) post-tensioned tendons at the corners of the beam are replaced by a bundle of tendons at the beam centroid in order to facilitate the field assembly. The resulting improvements of seismic performances are experimentally demonstrated by 10 cyclic tests of two full-scale SCPC beam-column connections. Numerical simulation of the proposed connection is conducted using the Open System for Earthquake Engineering Simulation (OpenSees) to replicate the experimental results. Seismic behaviors are taken into account, such as the gap opening/closing at the beam-column interface, the self-centering capacity, and the friction energy dissipation. Good agreement is observed between the numerical simulation and the test results. The proposed SCPC connection with bolted WFDs is demonstrated to have good performance when subjected to cyclic loading. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) are a subtype of small regulatory RNAs that are involved in numerous biological processes through small RNA-induced silencing networks. In an attempt to explore the phylogeny of mi RNAs across five platyhelminths, we integrated annotated mi RNAs and their full genomes. We identified conserved mi RNA clusters and, in particular, miR-71/2 was conserved from planarian to parasitic flatworms and was expanded in free-living Schmidtea mediterranea. Analysis of 22 mi RNA loci provided compelling evidence that most known mi RNAs are conserved across platyhelminths. Meanwhile, we also observed alterations of known protein-coding genes flanking mi RNA(s), such as transcriptional direction conversion and locus relocation, in around ~ 41% of 22 known mi RNA loci. Compared with Echinococcus multilocularis, the majority of these events occurred in evolution-distant Hymenolepis microstoma, Schistosoma japonicum or/and S. mediterranea. These results imply rearrangement events occurred near the known mi RNA loci. [ABSTRACT FROM AUTHOR]