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The ceramic composites of Sm 1- x Bi x CrO 3 (x = 0, 0.1, 0.2, 0.3) have been prepared by solid state reaction. X-ray diffraction patterns demonstrate that Bi-doped polycrystalline samples match with standard pattern of SmCrO 3. After Bi doping, the lattice constants in three directions increase slightly. The thermal expansion properties were studied by X-ray powder diffraction over the temperature range from 100 to 400 K. The results showed that the compound SmCrO 3 exhibits positive thermal expansion behavior in the a and c directions in the whole measurement temperature range. The anomaly is that in the b direction the lattice exhibits positive thermal expansion behavior at low temperatures, while above 200 K it exhibits near zero thermal expansion behavior. The thermal expansion behaviors of all Bi-doped SmCrO 3 are similar to that of SmCrO 3 , but unexpectedly, negative thermal expansion behaviors were observed in the b direction above 200 K in the highly Bi doped samples. The dielectric measurement shows that there are two thermal activation processes in all Sm 1- x Bi x CrO 3 (x = 0, 0.1, 0.2, 0.3) respectively, with the low-temperature activation corresponding to the grain itself, while the high-temperature activation comes from the grain boundary. After low-temperature thermal activation, with increasing temperature, the enhanced vibration of the corner oxygen atoms of the CrO 6 octahedron is mainly perpendicular to the b axis, which leads to the near zero thermal expansion behavior in the b direction. Moreover, after high-temperature thermal activation, as the temperature increases, the enhanced interaction between Bi3+ and the free oxygen atom (space oxygen atom) at the grain boundary will further lead to the negative thermal expansion behavior in the b-direction of the high concentration doped samples. [ABSTRACT FROM AUTHOR]

Nanomaterials with unique structures and functions have been widely used in the fields of microelectronics, biology, medicine, and aerospace, etc. With advantages of high resolution and multi functions (e.g., milling, deposition, and implantation), focused ion beam (FIB) technology has been widely developed due to urgent demands for the 3D fabrication of nanomaterials in recent years. In this paper, FIB technology is illustrated in detail, including ion optical systems, operating modes, and combining equipment with other systems. Together with the in situ and real-time monitoring of scanning electron microscopy (SEM) imaging, a FIB-SEM synchronization system achieved 3D controllable fabrication from conductive to semiconductive and insulative nanomaterials. The controllable FIB-SEM processing of conductive nanomaterials with a high precision is studied, especially for the FIB-induced deposition (FIBID) 3D nano-patterning and nano-origami. As for semiconductive nanomaterials, the realization of high resolution and controllability is focused on nano-origami and 3D milling with a high aspect ratio. The parameters of FIB-SEM and its working modes are analyzed and optimized to achieve the high aspect ratio fabrication and 3D reconstruction of insulative nanomaterials. Furthermore, the current challenges and future outlooks are prospected for the 3D controllable processing of flexible insulative materials with high resolution. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the association between baseline symptoms and changes in depressive symptoms and stroke incidents. Methods: We used data from the Chinese Health and Retirement Longitudinal Study conducted in 2013, 2015, and 2018. In total, 10,100 individuals aged ≥45 years and without a history of stroke in 2013 were included. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studied Depression scale (elevated depressive symptoms cutoff ≥10). Changes of depressive symptoms were assessed by two successive surveys (stable low/no, recent onset, recently remitted, and stable high depressive symptoms). We assessed whether baseline depressive symptoms and changes of them were associated with stroke incidents reported through 2018. Logistic regression analyses adjusted for age, gender, education, marital status and other potential confounders were performed. Results: For the analysis of baseline depressive symptoms and stroke (n = 10,100), 545 (5.4%) reported stroke incidents in the following 5-year period. Individuals with elevated depressive symptoms in 2013 experienced a markedly higher stroke risk (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.28–1.84) compared with those without elevated depressive symptoms. In the analysis of changes in depressive symptoms (n = 8491, 430 (5.1%) stroke events), participants with stable high (OR = 2.01, 95% CI = 1.58–2.56) and recent-onset (OR = 1.39, 95% CI = 1.04–1.85) depressive symptoms presented higher stroke risk compared to those with stable low/no depressive symptoms, while recently remitted symptoms (OR = 1.12, 95% CI = 0.80–1.57) were not associated with stroke risk. Conclusions: In conclusion, stable high and newly started depressive symptoms were associated with increased stroke risk, whereas the improvement of depressive symptoms was not related to increase in stroke risk, suggesting that stroke risk may be decreased by effective management of depressive symptoms. [ABSTRACT FROM AUTHOR]

With the advent of the era of big data, data mining has become one of the key technologies in the field of research and business. In order to improve the efficiency of data mining, this paper studies data mining based on the intelligent recommendation system. Firstly, this paper makes mathematical modeling of the intelligent recommendation system based on association rules. After analyzing the requirements of the intelligent recommendation system, Java 2 Platform, Enterprise Edition, technology is used to divide the system architecture into the presentation layer, business logic layer, and data layer. Recommendation module is divided into three substages: data representation, model learning, and recommendation engine. Then, the fuzzy clustering algorithm is used to optimize the system. After the system is built, the performance of the system is evaluated, and the evaluation indexes include accuracy, coverage, and response time. Finally, the system is put into a trial operation of an e-commerce platform. The click-through rate and purchase conversion rate of recommended products before and after the operation are compared, and a questionnaire survey is randomly launched to the platform users to analyze the user satisfaction. The experimental data show that the MAE of this system is the lowest, maintained at about 0.73, and its accuracy is the highest; before the recommended threshold exceeds 0.5, the average coverage rate of this system is the highest: 0.75; in Q1–Q5 subsets, the shortest response time of the system is 0.2 s. Before and after the operation of the system, the average click-through rate increased by 11.04%, and the average purchase rate increased by 9.35%. Among the 1216 users, 43% of the users were satisfied with 4 and 9% with 1. This shows that the system algorithm convergence speed is fast; it can recommend products more in line with user needs and interests and promote higher click-through rate and purchase rate, but user satisfaction can be further improved. [ABSTRACT FROM AUTHOR]

Focused ion beam (FIB) has been invented for several decades and widely utilized as a result of rapid development of integrated circuit industry and nanotechnology. Together with high resolution scanning electron microscopy (SEM), FIB can realize controllable micro-nano fabrication of metals and semiconductors. However, it is very difficult to guarantee the machining precision and quality when we extend the application to flexible materials. Severe damages such as the local thermal effect and chemical evolution will be induced with high-energy FIB bombarding on the flexible sample, so current models of FIB fabrication are no longer valid. In this paper, a practical 3-D FIB power deposition model was developed for studying the temperature rising mechanism and the according thermal evolution to realize controllable high-precision fabrication of flexible samples. Based on theories of ion transportation and ion-solid interaction, a new 3-D power deposition model including ion energy, aberrations, and Coulomb force among ions was built with Runge-Kutta method and Monte Carlo simulation. Thermal evolution of the representative flexible sample polydimethylsiloxane (PDMS) was studied with the finite element COMSOL-Multiphysics according to Fourier law of heat conductivity. The new model was improved by studying thermal effect under different dwelling times and beam currents, and verified by the related experiments. Results show that the local thermal effect of PDMS is very severe for high current density 30 keV Ga+ as its power density spatially can be compressed to 10 9 W / cm 3 . Fabrication experiments on FIB-SEM system are in good agreement with simulations of heat accumulation and thermal evolution of polymer PDMS. This work will improve controllability and precision of FIB fabrication on the flexible sample by considering the incident beam and the sample thermal effect together. [Display omitted] • A practical 3-D power deposition model is built for FIB processing flexible samples. • Model adaptability is improved by studying thermal effect under beam currents. • Model is verified and in good agreement with FIB experiments. • Controllable high-precision fabrication is realized with the new model. [ABSTRACT FROM AUTHOR]

We theoretically investigate the spin-orbit interaction effects on the Andreev reflection and the spin accumulation in a quantum dot embedded in an Aharonov-Bohm interferometer. Due to the spin-dependent phase caused by the spin-orbit (SO) interaction, the electron occupation number becomes spin dependent and the spin accumulation can appear in the quantum dot (QD). Furthermore, in the presence of a magnetic flux, the spin accumulation of the dot can even be reversed by tuning the gate voltage. The magnitude and direction of the spin accumulation in the QD can be easily controlled by the gate voltage, magnetic flux, and the SO interaction. The Andreev reflection current also exhibits a spin polarization under the influence of both the spin-orbit interaction and the magnetic field through the ring. The spin polarization of the current can be tuned by varying the spin-orbit interaction strength and the magnetic flux. This provides an efficient mechanism to control the spin accumulation and the Andreev reflection in the quantum dot. [ABSTRACT FROM AUTHOR]

Two ferromagnetic transitions have been found by temperature dependence ac susceptibility experiments on as-prepared bulk polycrystalline La0.9Ba0.1MnO3. Investigation indicates that the higher temperature transition (TCh) can be attributed to the oxygen excessive phase La0.9Ba0.1MnO3+δ at the surface, while the lower temperature transition (TCl) can be attributed to the interior stoichiometric phase La0.9Ba0.1MnO3 of the samples. Softening of ferromagnetic system near TCl has been observed in La0.9Ba0.1MnO3, which can be explained by the freezing of misorder of metal ion at higher temperature. [ABSTRACT FROM AUTHOR]

La 0.5 Cr 0.5 TiO 3+δ ceramic sample was prepared via traditional solid-state reaction route. Frequency and temperature dependence of dielectric permittivity were studied in the range of 10 2 ~ 10 6 Hz and of 77 ~ 360 K, respectively. It was observed that extraordinarily high low-frequency dielectric constants appeared at room temperature, and dielectric relaxation peaks shifted to higher temperature with increasing frequency. In the dc-bias studies, it was also found that the dielectric permittivity had obviously dc-bias dependence in low frequency, but independence as the frequency above 14 kHz. Interestingly, the dielectric characteristics of the sample had obvious light dependence at room temperature within the measured frequency range. The results demonstrate that visible light improves the dielectric properties of the ceramic by means of I–V and complex impedance analysis. [ABSTRACT FROM AUTHOR]

Abstract: Polycrystalline Si-added TbMnSi x O3 (x=0.05, 0.1) and Si-doped Tb1−x MnSi x O3, TbMn1−x Si x O3 (x=0.05, 0.1) samples were fabricated by a conventional solid-state reaction. The dielectric properties of ceramics have been investigated in a temperature range of 77–350K and a frequency range of 0.1−200kHz. Especially, an extraordinarily high low-frequency dielectric constant (~105) at room temperature was observed in TbMnSi0.1O3, and the values of at other frequencies can reach around 104. It turns out that the addition of element Si changes dielectric properties of TbMnO3 remarkably. Through the measured data of complex impedance, bulk contribution and grain boundary effects to electrical response are identified by the analysis of complex plane diagrams (Nyquist diagram). [Copyright &y& Elsevier]

Using a vapor liquid solid method with Au as the catalyst and a Si substrate as the Si source, high temperature annealing under atmospheric pressure resulted in a series of SiOx nanoflowers and nanobangles. The growth process and mechanism were investigated by comparing the morphologies of the nanoflowers grown using different annealing conditions. Triangular etch pits over ten micrometers in size were found scattered on the substrates, around which different SiOx nanoflowers had developed dozens of micrometers away. Photoluminescence measurements of the nanoflowers demonstrated that the luminous intensities increased with the increasing length and amount of the nanoflowers' petals. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the resistance switching (RS) effect of metal/Nb-doped SrTiO3 interfaces under different treating conditions. Two types of I–V characteristics appeared due to the modification of Schottky-like barrier and the formation of insulating layer. According to X-ray photoelectron spectroscopy analysis, the change in interface potential barrier was contributed to the migration of oxygen vacancies and electrons trapping/detrapping of carriers in the vicinity of interface. Nonlinear fitting is applied to the curves to study the conduction mechanism of metal/NSTO. For “barrier height” style, Schottky emission and Poole–Frenkel (P–F) emission are dominating; for “insulating layer” style, space-charge-limited current, controls the conduction. [Copyright &y& Elsevier]

Abstract: Low-frequency (0.1–200kHz) dielectric properties of Tb1−x Ga x MnO3 and TbGa y Mn1−y O3 (x, y =0.05, 0.1, 0.2, 0.3, 0.4) ceramic composites, which were synthesized by conventional solid-state reaction, were investigated in the temperature range from 77 to 350K. Both dielectric constants and loss tangent (tan δ) increase with increasing temperature and decrease with increasing frequency, respectively. Interestingly, the dielectric constants of Tb1−x Ga x MnO3 are as large as that of the parent TbMnO3, while the loss tangent reduces remarkably and less than 1 at high frequencies. These improvements demonstrate that Ga doped TbMnO3 may have potential applications. [Copyright &y& Elsevier]

Abstract: Cation deficient polycrystalline Tb1−x MnO3 (x= 0.05, 0.10) and TbMn1−y O3 (y =0.05, 0.10) samples were fabricated by conventional solid-state reaction. The complex dielectric properties of the cation deficient TbMnO3 were investigated as the function of temperature (77K≤T≤350K) and frequency (100Hz≤ f≤ 200kHz) separately. Compared to the parent TbMnO3, the cation deficient TbMnO3 samples exhibit not only high dielectric constant but also low dissipation factor. Nyquist plots of complex impedance show that the dielectric properties originate from two main relaxation sources, i.e. bulk contributions and grain boundary effects. [Copyright &y& Elsevier]

Abstract: TbMnO3/n-Si (n–N) and TbMnO3/p-Si (p–n) heterojunctions were fabricated under identical conditions. Good rectifying characteristics were found with almost the same forward current–voltage behavior in a temperature range from 150 to 300 K. Such intriguing superposed rectifying behaviours at the interfaces between TbMnO3 and Si of two different doped types can be explained by a similar Schottky barrier diode behavior with its current–voltage dependence generally dominated by only one type of carrier. This work will favor both electronic transport analysis and future device applications. [Copyright &y& Elsevier]

Abstract: Low-frequency (102–105 Hz) dielectric properties of TbMnO3+xTiO2 (x=0.33, 1, 3) ceramic composites, which were fabricated by conventional solid-state reaction, were investigated from 360 to 77K. Very high dielectric constants and interesting temperature dependence of the dielectric properties were observed in the present composite ceramics. When compared to the high dielectric loss of the polycrystalline TbMnO3, the loss of TbMnO3+xTiO2 (x=0.33, 1, 3) decreased with the increasing TiO2. Especially for TbMnO3+1TiO2, the dielectric loss decreased remarkably, while the dielectric constant was still very high, which are more favorable for practical applications. [Copyright &y& Elsevier]

Abstract: A non-contact method for the measurement of rotor speed and direction based on a quadrant photoelectric detector was proposed and the corresponding device was developed. The device can measure the speed of the rotor and its direction. Experimental results show that the device can get rid of both electronic noise and external disturbances effectively, and it can also avoid the effect of the change of optics facular intensity. The measurement range is 1–200,000rpm, and the relative error is 0.001%. [Copyright &y& Elsevier]

Abstract: We have fabricated different heterojunctions by pulsed laser depositing different thickness films of TbMnO3(TMO) on single crystal Nb-1.0 wt.%-doped SrTiO3 substrates. In addition to all those heterojunctions showing good rectifying properties, the most interesting phenomena are thickness-dependent backward diodelike behavior at low temperatures. Especially, when TMO film thickness is 40 nm, the normal diodelike behavior are found in a wide temperature range from 25 to 350 K, and the rectifying behaviors are nearly independent of temperature below 300 K. When TMO film thickness is 60 nm, the backward rectifying behaviors are nearly independent of temperature below 200 K. This work implies that various rectifying properties can be gotten in the same manganite based diodes by controlled different parameters. [Copyright &y& Elsevier]

Abstract: Low-frequency (102–105 Hz) dielectric properties of TbMnO3 (TMO) composites adding different cations were investigated from 360 to 77K. Compared to the parent TMO, it was found that cation addition could reduce dissipation factor, while very high dielectric constant almost remained. Especially addition of Ti ion reduced dissipation factor remarkably. And the additions of Sr ion and Ti ion at the same time resulted in the increase of dissipation factor. It is interesting that dissipation factor decreased again when Sr ion was partly substituted by Ba ion. [Copyright &y& Elsevier]

Abstract: Au/Ag/Al/In contacts to Nb-1.0wt.%-doped SrTiO3 (NSTO) were investigated. The contacts of the Au/Ag/Al electrodes which were grown by magnetic controlled sputtering techniques were not ohmic. After annealing at different temperatures in oxygen for 30min, better Schottky barriers could be formed in the contacts of Ag/NSTO and Au/NSTO. However, the ohmic contacts of indium to rough surface of NSTO are easy to obtain by pressing, and that to the polished surface can be obtained by melting indium with high vacuum. The specific contact resistances for different metal contacts were measured, the ohmic contacts of indium to NSTO by the two method almost have the same specific contact resistance, which is approximately 8.0×10−7 Ωm2. [Copyright &y& Elsevier]

Abstract: Anomalous annealing behaviors of insulator-metal transition temperature (T P) and ac magnetic susceptibility were investigated in different prepared polycrystalline La0.67Ba0.33MnO3 bulk samples which were annealed in a flow of 95%Ar:5%H2(AH) at 700°C for different time, and the behaviors were effects of oxygen loss and Ba ion vacancies. The experiments indicated that different prepared samples had different speed of oxygen loss and Ba ion vacancies during AH annealing. Different prepared samples had different content of structure defects, especially for the quenching samples, in which there were high stress and high defect content, the speed of oxygen loss and Ba2+ vacancies were the fastest during AH annealing, that was to say that quenching promote the hydrogen annealing effects on polycrystalline La0.67Ba0.33MnO3 compound. [Copyright &y& Elsevier]

Abstract: The low-frequency (103–105 Hz) dielectric properties of polycrystalline MgB2 were investigated as a function of temperature (25–285K). The real and imaginary parts of the dielectric constants were higher than 107, and they increased with the decreased temperature. No obvious frequency dependence of the real parts was found, which was consistent with the behavior of a good metal within the Drude model at low frequency. The results indicated the high dielectric constants were from the electrical conductivity of the superconductor. [Copyright &y& Elsevier]

Abstract: Polycrystalline bulk perovskite TbMnO3 were synthesized by conventional solid-state reaction, magnetic and transport and dielectric properties were examined, antiferromagnetism was observed near 10K, and semiconductor transport behaviour was found within measurable temperature range. Especially, an extraordinarily high low-frequency dielectric constant (∼104) near room temperature was observed, but below 200K the constant sharply decrease to less than 100, two apparent dielectric relaxations appeared in loss tangent, which was interpreted by the hopping of localized carriers and the thermally excited relaxation process. [Copyright &y& Elsevier]

Abstract: Upon annealing polycrystalline La0.67Ba0.33MnO3 bulk samples in flowing 95%Ar:5%H2 mixed gas at 700°C for different time, the insulator–metal transition temperature, and the amplitude of AC magnetic susceptibility were decreased first, then increased, finally decreased again. While the resistivity was increased monotonically. This anomalous behavior was explained by the combinational effects of oxygen loss and Ba ion vacancies caused by the segregation of Ba ion related impurity phase. [Copyright &y& Elsevier]

Dosing‐time–dependent changes in the effect and toxicity of morphine were examined in mice housed under alternating 12 h light (07:00 to 19:00 h) and dark (19:00 to 07:00 h) cycles. Morphine (0.5 mg/kg) was injected intraperitoneally (i.p.) in animals to assess its beneficial effect ( i.e. , protection against the kaolin‐induced, bradykinin‐mediated, writhing reaction) and its toxicity ( i.e ., alteration of the hepatic enzymes of aspartate aminotransferase [AST] alanine aminotransferase [ALT], and glutathione [GSH] in separate experiments). The magnitude of the analgesic effect of morphine depended on dosing time, with minimum effect at 02:00 h and maximum effect at 14:00 h. The serum hepatic enzyme levels of AST and ALT increased after dosing morphine (100 mg/kg) at 02:00 and 14:00 h. Time courses of these enzymes did not differ between the two trials. However, hepatic GSH, which is involved in the detoxification of chemical compounds, significantly decreased after i.p. morphine injection at 02:00 but not at 14:00 h. Overall, the results suggest that the analgesic effect of morphine is greater after dosing during the resting than during the activity phase of mice that have been induced with bradykinin‐mediated pain. Drug‐induced hepatic damage as inferred by GSH alteration, however, may be greater after dosing during the active phase. [ABSTRACT FROM AUTHOR]

Abstract: Epitaxial TbMnO3 films have been fabricated on SrTiO3(001) and LaAlO3(001) substrates by pulsed laser deposition (PLD), the structure and surface morphology of the films were characterized by X-ray diffraction with CuKα radiation and atomic force microscopy. The electrical transport and magnetic properties of the TbMnO3 films and bulk were examined, the resistivity and the forbidden band width Eg change with epitaxial orientation, semiconductor transport properties are found in the films and bulk, the average of the Eg of the films on SrTiO3 and on LaAlO3 is equal to the Eg of the bulk. The two TMO films have different magnetization mode, the magnetization of the film on SrTiO3 have an analogy to that of TbMnO3 single crystal. [Copyright &y& Elsevier]

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00 h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00 h or 20:00 h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00 h than 08:00 h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon. [ABSTRACT FROM AUTHOR]

We previously showed that the kaolin-induced writhe reaction exhibits 24h variation with a peak at the end of the resting period (14:00-18:00h) in mice maintained under light from 07:00 to 19:00h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.5 mg/kg) was given orally to mice at 02:00, 08:00, 14:00, or 20:00h, and the suppressive effect on kaolin-induced writhing was determined after each timed dosing. After dosing at 08:00h, indomethacin remarkably reduced the number of writhes during the critical span of 14:00-18:00h-the time when writhing reaction was greatest during the 24h, while the suppressive effect of the medicine after dosing at the other clock times was relatively small. These data suggest the analgesic effect of indomethacin in mice with the kaolin-induced writhing is greater after dosing in the early resting period, which is similar to that reported in patients with nocturnal pain. The kaolin-induced pain mouse model seems to be useful for the chronopharmacodynamic evaluation of analgesic agents. [ABSTRACT FROM AUTHOR]

The ceramic composites of Sm (1- x) Zn x CrO 3 (x = 0, 0.05, 0.1, 0.2) and SmZn y Cr (1- y) O 3 (y = 0, 0.05, 0.1, 0.2) were synthesized by solid state reaction. The complex dielectric properties of the ceramic samples were investigated as a function of temperature (77 K–350 K) and frequency (0.5 kHz–1000 kHz) separately. In all these ceramic samples, dielectric constants increase gradually with increasing temperature in the range of 77 K–150 K, and sharp increase in the range of 150 K–200 K, then exhibit plateaus in 200 K–350 K, in which present huge dielectric constants (~104). While the loss tangents (tan δ) undulate with temperature and show two peaks corresponding to the two relaxations. Obviously, the dielectric constants of Zn-doped samples are larger than that of the pristine SmCrO 3 , meanwhile the values of dielectric loss are smaller than that of the pristine one at room temperature and high frequency region. Impedance analysis reveals that the electrical relaxation processes can be attributed to the combined actions of grain and grain boundary effects, which lead to these improvements in Zn-doped SmCrO 3. • The ceramic compositeswere synthesized by solid state reaction. • X-ray diffraction patterns for all the samples almost match with standard pattern of SmCrO 3. • The dielectric constants increase with increasing temperature and reach plateaus at higher temperature. • The loss tangents undulate with temperature and show two peaks corresponding to the two relaxations. • Impedance analysis reveals that the electrical relaxation can be attributed to grain and grain boundary effects. [ABSTRACT FROM AUTHOR]

GLS4 is a first‐in‐class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co‐administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically‐based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single‐dose, multiple‐dose, food effects, and drug–drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co‐administered with ritonavir; co‐administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co‐administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Previous studies involving risk–benefit analysis of trastuzumab deruxtecan (DS‐8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS‐8201.A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non‐Randomized Studies tool, and then performed a meta‐analysis with R version 4.2.1.A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all‐grade treatment‐emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all‐grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively.This comprehensive summary of the incidence of TEAEs associated with DS‐8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS‐8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs. [ABSTRACT FROM AUTHOR]

Abstract: Effects of moisture absorption on capacitance–loss and current–voltage characteristics of LaMnO3+ δ /SrTiO3:Nb heterojunction had been investigated after the heterojunctions were exposed to ambient air. The moisture-absorption-induced increases in loss tangent and breakdown voltage were observed, whereas no changes were found on capacitance and diffusion voltage. These results were discussed by the decrease of oxygen ions in LaMnO3+ δ and the generation of hydroxide ions at grain boundaries. This work will favor both electronic transport analysis and future device applications. [Copyright &y& Elsevier]

Abstract: In/SrTiO3/SrTiO3:Nb capacitors have been fabricated by depositing SrTiO3 thin film on Nb-1 wt%-doped SrTiO3 substrate and using In as the top electrode. The current–voltage characteristics were measured and backward rectifying characteristics are found below room temperature. The interesting observation is that at constant negative bias the leakage current increases with decreasing temperature below 150 K. Analysis shows that the abnormal increasing current was determined by the tunneling process through the SrTiO3/SrTiO3:Nb junction. This work demonstrates that tunneling diode may be realized in homologous perovskite oxides and engineered by distortions and defects. [Copyright &y& Elsevier]

The Au/Nb-1.0 wt %-doped SrTiO3 junctions were successfully fabricated by magnetic controlled sputtering and annealing process. Backward diodelike behaviors were observed in as-prepared junction and the one annealed at 350 °C. Transition to Schottky behavior was found in the junction annealed at 750 °C; the Schottky junction shows linear capacitance-voltage (C-2-V) relationship in the reverse condition with barrier heights determined to be 1.6 eV. The results of current-voltage (I-V) measurements reveal that high temperature annealing can alter interface barrier and thereby ameliorate the stability of leakage current remarkably. [ABSTRACT FROM AUTHOR]

Abstract: In this work, Schottky junctions of Ag/Nb-1.0wt%-doped SrTiO3 (NSTO) have been fabricated by magnetic controlled sputtering technique and annealing process after sputtering. The junction between these two materials exhibits good Schottky rectifying behavior after high-temperature annealing, and the capacitance–voltage characteristics show linear C −2–V relationships in the reverse condition. The barrier heights were determined to be 2.75eV or so by current–voltage and capacitance–voltage methods, respectively. I–V characteristics revealed that high-temperature annealing in oxygen at 700°C alters this thin surface barrier, reduces the leakage current remarkably. [Copyright &y& Elsevier]

Abstract: Using a two-step growth technique, simple oxide heterostructures have been fabricated by pulsed laser depositing epitaxial La2CuO4 (LCO) thin films on Nb-0.7wt%-doped SrTiO3 (NSTO) substrates. The junctions show good rectifying behavior at all measuring temperatures and an obvious temperature dependence of current–voltage (I–V) properties in the range of 25–300K, which are discussed in relation to the p–n model. [Copyright &y& Elsevier]

Abstract: Different cation deficiency doped La0.85Ba0.1MnO3 and La0.9Ba0.05MnO3 and La0.9Ba0.1Mn0.95O3 and stoichiometric La0.9Ba0.1MnO3 polycrystalline bulk samples were synthesized at 1500°C, the ac magnetic susceptibility, resistivity and magnetic resistance (MR) of the samples were tested, and it is found that stoichiometric phase La0.9Ba0.1MnO3 sample have the highest ferromagnetic transition temperature T c, and La0.9Ba0.05MnO3 sample have the lowest ferromagnetic transition temperature T c. La0.85Ba0.1MnO3 sample have the largest magnetic resistance (MR), except La0.9Ba0.05MnO3 sample, the other samples have the same MR peak temperature. [Copyright &y& Elsevier]

Microstructure features including the morphology and texture of constituent phases play an important role in the mechanical properties of Ti-55531 high strength titanium alloy. However, the underlying understanding from the micromechanical aspect is still lacking. In the present work, the effect of microstructure on the micromechanical behavior of Ti-55531 alloy was investigated by high-energy X-ray diffraction. For two typical microstructures of Ti-55531 alloy, the micromechanical behavior including lattice strains of oriented grains are determined. Furthermore, the stress partitioning between α and β phase and internal microstress evolution in the specimens with different microstructures are discussed. In combination with the microstructure characterization, the corresponding mechanism for microstructure influence on the mechanical properties is discussed. It is found that, for the specimens with different types of microstructures, stress partitioning between constituent phases is obviously different. The results show that the α phase stress is higher than that of β phase in the specimen with the bimodal microstructure (BM), while the β phase is subjected to much higher stress than α phase in the specimen with the lamellar microstructure (LM). For the specimen with BM, the morphology of α phase leads to a remarkable difference in the microscopic deformation behavior between α p (primary α phase) and α s (secondary α phase). It is suggested that the acicular α s precipitates bear higher stress than equiaxed α p. The intergranular and interphase microstresses in both specimens have been quantitatively evaluated. The results show that the <200>//LD fiber texture of β phase leads to higher intergranular microstress in the specimen with BM. The interphase microstress is more remarkable in the specimen with LM. Combining the in-situ HEXRD and microstructure characterization, the present study provides a fundamental understanding of the relationship between microstructure and mechanical properties from the perspective of micromechanical behavior. [ABSTRACT FROM AUTHOR]

C-type lectin-like receptor-2 (CLEC-2) is a member of the C-type lectin superfamily of cell surface receptors. The first confirmed endogenous and exogenous ligands of CLEC-2 are podoplanin and rhodocytin, respectively. CLEC-2 is expressed on the surface of platelets, which participates in platelet activation and aggregation by binding with its ligands. CLEC-2 and its ligands are involved in pathophysiological processes, such as atherosclerosis, cancer, inflammatory thrombus status, maintenance of vascular wall integrity, and cancer-related thrombosis. In the last 5 years, different anti- podoplanin antibody types have been developed for the treatment of cancers, such as glioblastoma and lung cancer. New tests and new diagnostics targeting CLEC-2 are also discussed. CLEC-2 mediates thrombosis in various pathological states, but CLEC-2-specific deletion does not affect normal hemostasis, which would provide a new therapeutic tool for many thromboembolic diseases. The CLEC-2-podoplanin interaction is a target for cancer treatment. CLEC-2 may be applied in clinical practice and play a therapeutic role. [ABSTRACT FROM AUTHOR]

Tafolecimab, a novel fully human monoclonal antibody targeting PCSK9, has been assessed in Chinese healthy volunteers and patients with hypercholesterolemia. This analysis is to develop and qualify a population pharmacokinetics (PopPKs)/LDL‐C model to characterize tafolecimab PK and LDL‐C profiles, evaluate the impact of potential covariates on tafolecimab, estimate individual predicted exposure, and LDL‐C decreasing, furthermore, explore exposure–response relationship to support clinical use. Data from six clinical trials in China were used to develop the PopPK/LDL‐C model. A Michaelis–Menten approximation of the target‐mediated drug disposition (TMDD) model was used to describe PK data and indirect response (IDR) model was developed to estimate the LDL‐C profile. A stochastic approximation expectation maximization algorithm was applied to estimate PopPK/LDL‐C parameters. The PK/LDL‐C time course data for tafolecimab were well described by TMDD/IDR model. Baseline covariates resulting in statistically significant changes in PK/LDL‐C parameters included: body weight and sex on absorption rate constant; body weight, sex, and unbound PCSK9 on central volume; body weight and sex on clearance; baseline LDL‐C on first‐order rate constants for the removal of an effect); and disease and sex on maximum effect. However, the magnitudes of changes associated with these covariates do not necessitate dose adjustment. Exposure–efficacy relationship indicated that the nadir of LDL‐C reduction achieved with the steady‐state trough plasma concentration (Ctrough) of tafolecimab at 5 μg/mL, and no further LDL‐C decreasing with the increasing Ctrough. There was no exposure dependency observed in exposure‐safety exploration. The PopPK/LDL‐C model was successfully developed, validated, and predicted tafolecimab/LDL‐C concentrations and individual exposures. [ABSTRACT FROM AUTHOR]

With the trend of electronic information technology towards miniaturization, integration and intelligence, higher requirements are put forward for the performance of dielectric ceramic materials. In this paper, a series of doped samples Sm 2 O 3 -xZnO (x = 0, 0.1, 0.2, 0.4, 0.6, 0.8) were successfully prepared by the traditional solid state reaction method, and the complex dielectric properties of the ceramic samples were investigated as a function of temperature (100 K–400 K) and frequency (102–106 Hz) separately. A new phase Zn 6.76 Sm 2.58 O 10.6 was found in all samples, and all samples were complex. At a higher temperature, 350 K, with the increase of ZnO doping content, the maximum dielectric constant is 434.7, the dielectric loss is as low as 0.0098, and the dielectric performance is significantly increased compared with room temperature. UV–Vis DRS test showed that the absorbance of the sample increased with the increase of ZnO content, and the side reaction showed that the dielectric constant and dielectric loss of the sample were improved under the action of UV light. These provide an experimental basis for the application of samarium based dielectric ceramics. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P <.001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11‐16.47, P <.001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP‐lowering and occurrence of adverse events between the three groups. [ABSTRACT FROM AUTHOR]

Elaborate design of highly active catalysts from earth-abundant elements is important for the development of water-splitting devices. We have synthesized {2̅ 1 1} high index-faceted Ni12P5 nanoplates and Ni12P5 spherical nanoparticles (SNPs) by the one-step solvothermal method. The Ni12P5 nanoplates show enhanced hydrogen evolution reaction activity with a lower overpotential of −128 mV and a smaller Tafel slope of 60.6 mV dec−1 compared to Ni12P5 SNPs. Stability tests reveal exceptional durability of the catalyst. This study offers an attractive catalytic material for large-scale hydrogen production technology. [ABSTRACT FROM AUTHOR]

In schizophrenia, the age at illness onset may reflect genetic loading and predict prognosis. We aimed to compare the pre-treatment symptom profiles and clinical symptom responses to antipsychotic treatment of individuals with late-onset schizophrenia (LOS; onset age: 40–59 years) with individuals with early-onset schizophrenia (EOS; onset age < 18 years) or typical-onset schizophrenia (TOS; onset age: 18–39 years). We conducted an 8-week cohort study in inpatient departments of five mental health hospitals in five cities in China. We included 106 individuals with LOS, 80 with EOS, and 214 with TOS. Their onset of schizophrenia was within three years and the disorders were minimally treated. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at baseline and after 8 weeks of antipsychotic treatment. Mixed effect models were used to compare symptom improvement within eight weeks. Antipsychotic therapy reduced all PANSS factor scores in all three groups. LOS had significantly better improvement in PANSS positive factor scores than EOS at week 8 after adjusting for sex, duration of illness, dose equivalents of antipsychotics at baseline, sites as fixed effects, and individuals as random effects. LOS was associated with reduced positive factor scores at week 8 when receiving 1 mg olanzapine dose equivalent per 1 kg body weight compared with EOS or TOS. In conclusion, LOS had better early improvement of positive symptoms than EOS and TOS. Thus, personalized treatment for schizophrenia should consider the age of onset. • Age of schizophrenia onset is not related to the pre-treatment severity of positive symptoms. • Late-onset schizophrenia is related to better improvement of positive symptoms at week 8 than the early-onset. • Patients with late-onset schizophrenia are more sensitive to antipsychotics. [ABSTRACT FROM AUTHOR]

Background: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. Methods and Results: To evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 μg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 μg/kg dose group obtained pharmacokinetic parameters: Cmax was 7.645 (24.21) ng/mL, AUC0–t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 μg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 μg/kg, the Cmax value at day 5 was 8.838 (51.6) ng/mL and the AUC0–t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild. Conclusions: It is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn) Identifier No. ChiCTR2000041107. [ABSTRACT FROM AUTHOR]

Background and Objective: There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers. Methods: The study consisted of single ascending doses part (part 1: 25–600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile. Results: In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (Tmax) of 1.50 to 3.00 h. The geometric median half-life (t1/2) of SHR2285 varied from 8.74 to 12.1 h across 25–600 mg single dose. Total systemic exposure of metabolite SHR164471 was approximately 1.77- to 3.61-fold that of the parent drug. The plasma concentration of SHR2285 and SHR164471 reached steady state by the morning of Day 7, with low accumulation ratio (0.956–1.20 and 1.18–1.56, respectively). The increase in pharmacokinetic exposure of SHR2285 and SHR164471 was less than dose proportional. Food has minimal effect on the pharmacokinetics of SHR2285 and SHR164471. SHR2285 produced an exposure-dependent prolongation of activated partial thromboplastin time (APTT) and a decrease in FXI activity. The maximum FXI activity inhibition rate (geometric mean) at steady state was 73.27%, 85.58%, 87.77% and 86.27% for 100–400 mg, respectively. Conclusions: SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile. ClinicalTrials.gov Identifier NCT04472819; registered on July 15, 2020. [ABSTRACT FROM AUTHOR]