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N‐acyl iminophosphoranes have shown significant potentials in various areas. This paper presents two electrochemical strategies for the successful construction of a series of substituted N‐acyl iminophosphoranes using electrochemical activation of hydroxylamines or dioxazolones to generate unprotected amide radicals and radical anions. The simple undivided cell with inexpensive electrode setups (graphite felts, carbon rods, and copper sheets) provides excellent substrates tolerance under mild conditions. This simple electrochemical construction of N‐acyl iminophosphoranes also has good scalability, practicability and extensibility. Furthermore, synthetic transformations of the N‐acyl iminophosphorane products have demonstrated the application potentials of the P=N bond. [ABSTRACT FROM AUTHOR]

Adebrelimab, a novel anti‐PD‐L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first‐line treatment for extensive‐stage small‐cell lung cancer in 2023. A two‐compartment model with empirical time‐varying CL for adebrelimab was established based on data from 263 patients receiving body weight‐based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti‐drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non‐responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure–response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight‐based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non‐invasive diagnosis method based on serum markers, such as α‐fetoprotein (AFP), and des‐γ‐carboxy‐prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere‐coated three‐dimensional (3D) hierarchical porous chip, named a SiO2‐chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non‐HCC and HCC subjects are enriched using an SiO2‐chip and performed RNA sequencing to identify HCC‐related long non‐coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT‐1 and EGFR‐AS‐1 are two HCC‐related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT‐PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy‐based approach for noninvasive and reliable HCC detection is developed. [ABSTRACT FROM AUTHOR]

The electromechanical properties of [001]‐textured Mn‐PMN‐PZT ceramics are characterized under a hydrostatic pressure of up to 400 MPa. The dielectric constant of textured ceramics increases first and then decreases as pressure increases. A comparison of the electromechanical constants sij, kij, and dij (i, j = 1, 3) obtained by the method of direct calculation and admittance fitting is displayed in this work. The results show that the two methods can obtain similar results at lower pressures. When the pressure is relatively high, the loss cannot be ignored, and the results of the two methods are quite different. The admittance fitting method gives a more accurate piezoelectric constant. Under 400 MPa, textured ceramics have k31 = 0.55, d31 = 321 pC/N, k33 = 0.89, and d33 = 702 pC/N, while random ceramics have k31 = 0.33, d31 = 92 pC/N, k33 = 0.71, and d33 = 230 pC/N. The large piezoelectric properties of textured ceramics under high pressure make them potential underwater transducers. [ABSTRACT FROM AUTHOR]

Design of a projecting‐receiving dual‐purpose transducer is challenging due to the difficulty of synthesizing piezoelectric materials with combinatory "soft" properties (high piezoelectric coefficient d) and "hard" properties (low dielectric loss and high mechanical quality factor Qm). In this study, we provide a different perspective to address this challenge via exploiting single‐crystal‐like electrostriction coefficient Q33 through the fabrication of grain oriented or textured "hard" piezoelectric ceramics. Mn‐doped 0.27Pb(In1/2Nb1/2)O3–0.41Pb(Mg1/3Nb2/3)O3–0.32PbTiO3 (Mn:PIN–PMN–PT) piezoelectric ceramics with a high [0 0 1]c texture fraction of 99% were synthesized, which exhibit three times greater piezoelectric properties (d33 ∼ 828 pC/N) than random counterparts (d33 ∼ 251 pC/N), while maintaining low loss (tan δ ∼ 0.5%, Qm = 443). According to the formula d33=2Q33Prε33${d}_{{\mathrm{33}}}{\mathrm{\ = \ 2}}{Q}_{{\mathrm{33}}}\ {P}_{\mathrm{r}}\ {\varepsilon }_{{\mathrm{33}}}$, the large improvement of d33 in textured ceramics is mainly due to a doubling increase in dielectric constant ε33 and Q33 (∼0.057 m4/C2). Notably, the Q33 exhibits remarkable similarity to that of PMN–PT single crystals, further contributing to the enhanced piezoelectric performance of textured ceramics. Phase field model of ferroelectrics was performed to understand the texturing on Q33 and elucidate the underlying mechanism at the domain level. The textured ceramics exhibit excellent combinatory "soft" and "hard" properties, which are the promising materials for developing projecting‐receiving dual‐purpose transducers with high efficiency and high sensitivity. [ABSTRACT FROM AUTHOR]

[001] textured 0.40BiScO3‐0.60PbTiO3‐0.125 mol%Nb5+ (BS‐60PT‐0.125Nb) high‐temperature piezoelectric ceramics were synthesized using templated grain growth process. A high texture degree F001 of 99% was obtained using 2 vol% BaTiO3 (BT) templates. The piezoelectric charge constant d33 and the unipolar strain under 40 kV cm−1 at room temperature for the textured ceramics are 646 pC N−1 and 0.36%, respectively, which is over two times as those for untextured ceramics (∼243 pC N−1 and 0.17%). The electrostriction Q33 value of the textured sample remarkably increased from 0.034 m4 C−2 to 0.068 m4 C−2 under 30 kV cm−1, showing a twice higher than untextured. Compared with random ceramics, the improvement piezoelectric response of the textured ceramics is primarily attributed to the increase of the dielectric constant εr and electrostriction coefficient Q33 along [001] orientation, which is originating from the anisotropy of piezoelectricity. The BS‐60PT‐0.125Nb textured ceramics have large piezoelectric response and ultrahigh electrostriction with high temperature stability (high depolarization temperature Td of ∼360°C and high Curie temperature Tc of 421°C), showing great potential for the piezoelectric applications at high temperatures. [ABSTRACT FROM AUTHOR]

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion. Methods: A single‐centre, open‐label, single‐arm, fixed‐sequence clinical trial in 18 patients with prostate cancer. Results: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (Cmax) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration–time curve (AUC0–t)was 20.577 and 7.320 h ng/mL, geometric mean AUC0–∞ was 20.949 and 7.451 h ng/mL, mean half‐life (t1/2) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean Cmax of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC0–t was 1003.896 and 380.158 h ng/mL, geometric mean AUC0–∞ was 1038.054 and 401.387 h ng/mL, mean t1/2 was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean Cmax of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC0–t was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC0–∞ was 15 218.158 and 5364.625 h ng/mL, mean t1/2 were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively. Conclusion: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half‐lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion. [ABSTRACT FROM AUTHOR]

Anlotinib is a small molecule of novel tyrosine kinase inhibitor initially approved to treat non‐small cell lung cancer in China. Drug–drug interaction (DDI) is an extrinsic factor important for the appropriate use of anlotinib in clinical practice. In vitro experiments demonstrated that anlotinib is a substrate of cytochrome P450 (CYP) enzymes and moderate inhibitor of several common ones; however, no clinical DDI studies have been performed to investigate inhibitory effects of anlotinib on these CYP enzymes. Thus, its drug label recommends avoiding co‐administration with substrates of these enzymes, which have narrow therapeutic windows. In this study, we performed a CYP450 inhibition study, followed by gathering in vitro and clinical pharmacokinetic data to build the first physiologically based pharmacokinetic (PBPK) model of anlotinib. The verified model was subsequently used to predict the DDI mediated by anlotinib. As a result, the marginal plasma exposure changes of typical CYP3A and CYP2C9 substrates were less than the bioequivalence threshold, indicating that anlotinib has a very low potential of causing clinically meaningful DDI through the inhibition of several major CYP enzymes. According to the FDA's latest guideline on DDI, the established model with the simulation results may support the revision of anlotinib labelling without further clinical studies, lifting unnecessary restrictions on anlotinib regimens. [ABSTRACT FROM AUTHOR]

Summary: High‐frequency force balance test is a major technical means to evaluate the wind effect of super high‐rise buildings. Most super high‐rise buildings have the characteristic that the first two‐order modal frequencies are close, and thus, considerable modal coupling effects (MCEs) may occur under wind load. For a balance model system (BMS), MCEs increase the difficulty of correcting aerodynamic distortion signals. For the wind‐induced vibration analysis of a structural system (PSS), the calculation results of the wind‐induced response and the equivalent static wind load (ESWL) may be significantly affected without considering MCE. Based on the above‐mentioned signal distortion of BMS and the modal coupling problem of PSS, this study proposes a wind‐induced vibration calculation method for the two coupled systems (BMS and PSS). The method uses the second‐order blind identification technique based on complex modal theory and the Bayesian spectral density method considering full aerodynamic characteristics to achieve effective correction of the distortion signal in BMS. In addition, it deduces the calculation method of the wind‐induced response and ESWL considering the three‐dimensional coupled vibration of a super high‐rise building. The wind effect calculation results of a 528‐m super high‐rise building confirm the necessity and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

High‐temperature capacitors have become an important research topic recently as commercially available capacitors cannot fulfill the new requirements from industry. In this work, a new ceramic ternary system (1 − x)[0.9Na0.5Bi0.5TiO3‐0.1BiAlO3]‐xNaNbO3 is introduced, and the effects of NaNbO3 concentration on macroscopic phase structure, locally disordered structure, dielectric properties, conduction properties, and energy storage properties are studied. At the optimum composition of x = 0.30, an ultrawide temperature range (−90 and 320 °C) covering both stable permittivity (Δε′/ε′25°C ≤ ± 15%) and low dielectric loss (tan δ ≤ 0.02) can be obtained. Additionally, this material has a high RC constant of 2.8 s and a high energy storage efficiency of 88% under the electric field of 60 kV cm−1 at room temperature. Therefore, this work provides a very promising candidate for dielectrics used in multilayer ceramic capacitors (MLCC) in an ultrawide operating temperature range. [ABSTRACT FROM AUTHOR]

The geometries and energetics of complexes of Hg(II) and Pb(II) with sulfur- and aminopyridine-containing chelating resin including crosslinked polystyrene immobilizing 2-aminopyridine via sulfur-containing (PVBS-AP), sulfoxide-containing (PVBSO-AP), and sulfone-containing (PVBSO-AP) spacer arms have been investigated theoretically, and thus interactions of the metal ions with chelating resins were evaluated. The results indicate that PVBS-AP behaves as a tridentate ligand to coordinate with the metal ions by S and two N atoms to form chelating compounds with S atom playing a dominant role in the coordination, whereas PVBSO-AP and PVBSO-AP interact with metal cations, respectively, in a tricoordinate manner by O and two N atoms forming chelating complexes. Furthermore, it is revealed that O and N2 atoms of PVBSO-AP are the main contributor of coordination to Hg(II), whereas N2 atom of PVBSO-AP is mainly responsible for the coordination to Hg(II). For PVBSO-AP-Pb and PVBSO-AP-Pb complex, the coordination is dominated by the synergetic effect of N1, N2, and O atoms. Natural bond orbital and second-order perturbation analyses suggest that the charge transfer from the chelating resins to metal ions is mainly dominated by the interactions of lone pair of electrons of the donor atoms with the unoccupied orbitals of metal ions. Hg(II) complexes exhibit larger binding energies than the corresponding Pb(II) complexes, implying the chelating resins exhibit higher affinity toward Hg(II), which is consistent with the experimental results. Combined the theoretical and experimental results, further understanding of the structural information of the complexes and the coordination mechanism was achieved. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011 [ABSTRACT FROM AUTHOR]