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Fungal infection threatens human health worldwide due to the limited arsenal of antifungals and the rapid emergence of resistance. Epidermal growth factor receptor (EGFR) is demonstrated to mediate epithelial cell endocytosis of the leading human fungal pathogen, Candida albicans. However, whether EGFR inhibitors act on fungal cells remains unknown. Here, we discovered that the specific EGFR inhibitor osimertinib mesylate (OSI) potentiates azole efficacy against diverse fungal pathogens and overcomes azole resistance. Mechanistic investigation revealed a conserved activity of OSI by promoting intracellular fluconazole accumulation via inhibiting Pdr5 and disrupting V-ATPase function via targeting Vma1 at serine 274, eventually leading to inactivation of the global regulator TOR. Evaluation of the in vivo efficacy and toxicity of OSI demonstrated its potential clinical application in impeding fluconazole resistance. Thus, the identification of OSI as a dual action antifungal with co-targeting activity proposes a potentially effective therapeutic strategy to treat life-threatening fungal infection and overcome antifungal resistance. [ABSTRACT FROM AUTHOR]

Hydrogen cyanide (HCN) is a crucial building block for various industrial chemicals in organic synthesis. Due to its high toxicity to humans and the environment, meticulous care is required in the synthesis, use, and disposal of HCN and its derivatives. This study investigated the premature failure of the HCN reactor, a core component of the HCN production system. Despite a design life of 20 years, the reactor experienced abnormal leakage after only 4 years of operation. Comprehensive investigations revealed that corrosion pits caused by localized corrosion formed at the circumferential welding seam of the reactor shell. This problem was further aggravated by vortex scouring from the pressurized water medium. Additionally, residual stress at the welding seam contributed to decreased toughness. The analysis highlighted the intricate relationship between localized corrosion and vortex scouring as the primary mechanisms leading to perforation and leakage of the reactor shell. Based on these findings, effective countermeasures were proposed to prevent similar future failures, potentially enhancing the operational safety and reliability of the HCN production system. • Premature failure of the HCN reactor occurred after only 4 years, despite a 20-year design life. • Localized corrosion pits formed at the circumferential welding seam of the reactor shell, leading to abnormal leakage. • Vortex scouring of pressurized water worsened the problem, highlighting the link between corrosion and hydraulic forces. • Proposed countermeasures aim to prevent similar failures, enhancing operational safety and reliability in HCN production. [ABSTRACT FROM AUTHOR]

• The purpose of this article is to study a power flow algorithm with strong convergence, initial value adaptability, and efficiency. • This paper proposes a two-part alternating iterative framework based on dynamic equivalent admittance. • The proposed algorithm has universality for well-and ill-conditioned systems. • The proposed method combines the convergence characteristics of the Z-bus Gauss method and Newton's method, so it is easy to implement based on existing program codes. Power flow is an extensively used tool in various operations and planning of power systems. In this paper, we propose an efficient hybrid method for solving the power flow problems in ill-conditioned power systems. This method is implemented in a framework of two-part alternating iteration. In Part I of this method, PV bus voltages are regarded as constant and PQ bus voltages are updated by the Z-bus Gauss method. In Part II of this method, PQ bus loads are equivalent to dynamic admittances, and PV bus voltage angles are updated by Newton's method. The values of PQ bus voltage magnitudes and PV bus voltage angles are passed between Part I and Part II. The proposed method is validated in well- and ill-conditioned systems and compared with several well-known power flow methods. Results show that the proposed method is robust and efficient to address the issues related with large-scale ill-conditioned power systems and it is not significantly affected by the considered initial guess. [ABSTRACT FROM AUTHOR]

• Main landing gear door of a civil aircraft underwent abnormal cracking during a flight test. • The crack initiated at the upper edge corner of the main landing gear door. • The assembly gap between the hinge joint and the upper edge of outer landing gear door was insufficient. • Internal defects in the sandwich composite structure of the landing gear door were also found. Among the myriad structural and moving components integral to civil aircraft, only a select few confront the dual challenges of meeting aerodynamic and mechanical performance criteria, a circumstance exemplified by landing gear doors. The failure of landing gear poses a substantial threat to both the structural integrity and the safety of an aircraft during flight. Surprisingly, the existing literature lacks an in-depth investigation into the failure of landing gear doors. This paper addresses this gap by examining the abnormal cracking failure observed in the main landing gear door of a civil aircraft. The purpose of this paper is to find out the root cause of the failure, so a comprehensive investigation of the landing gear outer door is carried out. This investigation employed various techniques, including computed tomography, three-dimensional scanning analysis, macroscopic and microscopic morphology analysis using optical microscopy, three-dimensional stereomicroscopy, scanning electron microscopy, and micro-area composition analysis using energy dispersive spectrometry. Through repeated sorting and comprehensive analysis of various failure forms and defects, the root causes of the main landing gear door failure were conclusively identified. Evidence revealed that the crack originated at the upper edge corner of the main landing gear door, precisely where abnormal contact and wear with the hinge joint occurred. Targeted countermeasures were proposed from aspects such as design, manufacturing, and installation, and the suggested improvements were adopted. [ABSTRACT FROM AUTHOR]

• The cyclic wetting and drying had a deterioration effect on the down-slope rock bridge, and it affected the failure mode. • AE multi-parameters exhibited obvious critical slowing down phenomenon before the failure. • The timeliness of the failure prediction for specimens with different cyclic wetting and drying was discussed. Down-slope rock bridge in slopes and dangerous rock masses are often affected by cyclic wetting and drying, leading to severe geological disasters. In order to investigate the deterioration mechanism, deformation failure mode and instability precursor information of sandstone down-slope rock bridge under different cyclic wetting and drying, uniaxial compression tests combined with acoustic emission (AE) tests were conducted. The failure of the specimen experienced four stages. As the number of the cyclic wetting and drying increased, the specimen's uniaxial compressive strength and elastic modulus decreased, and the failure mode transitioned from tensile to shear. Utilizing the critical slowing down theory, the variance and autocorrelation coefficient curves of AE multi-parameters were analyzed. The abrupt change of RA value, RA/AF value, and b value at the crack damage stress point and the abrupt change of the peak frequency lagging behind the crack damage stress point can be used as the precursors of instability. The instability precursor identified based on the peak frequency variance is closer to the specimen's peak stress point and can be used for short-term failure prediction. The autocorrelation coefficient curve of AE multi-parameters aligned with the variance curve, indicating that with an increased number of cyclic wetting and drying, the instability precursor appeared earlier, leading to a larger failure prediction time interval. [ABSTRACT FROM AUTHOR]