Unveiling Vacuolar H+-ATPase Subunit a as the Primary Target of the Pyridinylmethyl-Benzamide Fungicide, Fluopicolide.

An estimated 240 fungicides are presently in use, but the direct targets for the majority remain elusive, constraining fungicide development and efficient resistance monitoring. In this study, we found that Pcα-actinin knockout did not influence the sensitivity of Phytophthora capsici to fluopicolide, which is a notable oomycete inhibitor. Using a combination of Bulk Segregant Analysis Sequencing and Drug Affinity Responsive Target Stability (DARTS) assays, the vacuolar H+-ATPase subunit a (PcVHA-a) was pinpointed as the target protein of fluopicolide. We also confirmed four distinct point mutations in PcVHA-a responsible for fluopicolide resistance in P. capsici through site-directed mutagenesis. Molecular docking, ATPase activity assays, and a DARTS assay suggested a fluopicolide-PcVHA-a interaction. Sequence analysis and further molecular docking validated the specificity of fluopicolide for oomycetes or fish. These findings support the claim that PcVHA-a is the target of fluopicolide, proposing vacuolar H+-ATPase as a promising target for novel fungicide development.

Excellent Energy-Storage Performance in Lead-Free Capacitors with Highly Dynamic Polarization Heterogeneous Nanoregions.

Lead-free dielectric ceramics with excellent energy-storage performance are crucial to the development of the next-generation advanced pulse power capacitors. However, low energy-storage density limits the evolution of capacitors toward lightweight, miniaturization, and integration. Here, an effective strategy of constructing highly dynamic polarization heterogeneous nanoregions is proposed in lead-free relaxors to realize an ultrahigh energy-storage density of ≈8.0 J cm-3 , making almost ten times the growth of energy-storage density compared with pure Bi0.5 Na0.5 TiO3 ceramic, accompanied by a higher energy efficiency of ≈80% as well as an ultrafast discharge rate of ≈20 ns. Ultrasmall polarization heterogeneous nanoregions with different orientations and ultrahigh flexibility, and significantly decreased grain size to submicron lead to reduced heat loss, improved breakdown electric field and polarization, enhanced relaxation, and delayed polarization saturation behaviors, contributing to the remarkable energy-storage performance. Moreover, the breakdown path distribution or electrical tree evolution behaviors are systematically studied to reveal the origin of ultrahigh breakdown electric field through phase field simulations. This work demonstrates that constructing highly dynamic polarization heterogeneous nanoregions is a powerful approach to develop new lead-free dielectric materials with high energy-storage performance.

Kalman filter-based model predictive control for drag-free satellite under actuator failures and input saturations.

This paper studies the problem of fault-tolerant control for the drag-free satellite subject to actuator failures and input saturations. Particularly, a new Kalman filter-based model predictive control method for the drag-free satellite is proposed. Based on the developed dynamic model and the Kalman filter strategy, a new fault-tolerant design scheme is presented for the challenging situation where the satellite is subject to measurement noise and external disturbance. With the designed controller, the robustness of the system can be guaranteed, and the problem caused by actuator constraints and faults can be solved. Finally, the correctness and effectiveness of the proposed method are verified by numerical simulations.

Adaptive Control for Gravitational Wave Detection Formation Considering Time-Varying Communication Delays.

A distributed six-degree-of-freedom (6-DOF) cooperative control for multiple spacecraft formation is investigated considering parametric uncertainties, external disturbances, and time-varying communication delays. Unit dual quaternions are used to describe the kinematics and dynamics models of the 6-DOF relative motion of the spacecraft. A distributed coordinated controller based on dual quaternions with time-varying communication delays is proposed. The unknown mass and inertia, as well as unknown disturbances, are then taken into account. An adaptive coordinated control law is developed by combining the coordinated control algorithm with an adaptive algorithm to compensate for parametric uncertainties and external disturbances. The Lyapunov method is used to prove that the tracking errors converge globally asymptotically. Numerical simulations show that the proposed method can realize cooperative control of attitude and orbit for the multi-spacecraft formation.

Continuous Low-Thrust Maneuver Planning for Space Gravitational Wave Formation Reconfiguration Based on Improved Particle Swarm Optimization Algorithm.

This study proposes a three-spacecraft formation reconfiguration strategy of minimum fuel for space gravitational wave detection missions in the high Earth orbit (105 km). For solving the limitations of measurement and communication in long baseline formations, a control strategy of a virtual formation is applied. The virtual reference spacecraft provides a desired relative state between the satellites, which is then used to control the motion of the physical spacecraft to maintain the desired formation. A linear dynamics model based on relative orbit elements' parameterization is used to describe the relative motion in the virtual formation, which facilitates the inclusion of J2, SRP, and lunisolar third-body gravity effects and provides a direct insight into the relative motion geometry. Considering the actual flight scenarios of gravitational wave formations, a formation reconfiguration strategy based on continuous low thrust is investigated to achieve the desired state at a given time while minimizing interference to the satellite platform. The reconfiguration problem is considered a constrained nonlinear programming problem, and an improved particle swarm algorithm is developed to solve this problem. Finally, the simulation results demonstrate the performance of the proposed method in improving the maneuver sequence distribution and optimizing maneuver consumption.

Attitude-Orbit Coupled Control of Gravitational Wave Detection Spacecraft with Communication Delays.

In order to meet the position and attitude requirements of spacecrafts and test masses for gravitational-wave detection missions, the attitude-orbit coordination control of multiple spacecrafts and test masses is studied. A distributed coordination control law for spacecraft formation based on dual quaternion is proposed. By describing the relationship between spacecrafts and test masses in the desired states, the coordination control problem is converted into a consistent-tracking control problem in which each spacecraft or test mass tracks its desired states. An accurate attitude-orbit relative dynamics model of the spacecraft and the test masses is proposed based on dual quaternions. A cooperative feedback control law based on a consistency algorithm is designed to achieve the consistent attitude tracking of multiple rigid bodies (spacecraft and test mass) and maintain the specific formation configuration. Moreover, the communication delays of the system are taken into account. The distributed coordination control law ensures almost global asymptotic convergence of the relative position and attitude error in the presence of communication delays. The simulation results demonstrate the effectiveness of the proposed control method, which meets the formation-configuration requirements for gravitational-wave detection missions.

Baseline sensitivity and control efficacy of a new QiI fungicide, florylpicoxamid, against Botrytis cinerea.

BACKGROUND: Gray mold caused by Botrytis cinerea is an airborne plant pathogen with a necrotrophic lifestyle that infects more than 200 crops worldwide. Florylpicoxamid is a second-generation picolinamide fungicide inspired by a natural product. Florylpicoxamid targets the Qi site of the mitochondrial cytochrome bc1 complex and is currently being registered in China for the control of gray mold in a variety of crops. Although a broad spectrum of activity and attributes have been reported for florylpicoxamid, little is known about its effectiveness against gray mold or its protective and curative properties. RESULTS: Florylpicoxamid exhibited substantial inhibitory activity against 12 tested species of plant-pathogenic fungi, with effective concentration for 50% growth inhibition (EC50 ) values ranging from 0.017 to 2.096 µg ml-1 . A total of 129 isolates of B. cinerea from ten regions were tested for their sensitivity to florylpicoxamid, and the mean EC50 value was 0.04 ± 0.017 µg ml-1 . Furthermore, florylpicoxamid was observed to substantially inhibit all developmental stages of B. cinerea, with mycelial development, sclerotium germination, germ tube elongation and conidial germination being restrained with an EC50 value of 0.051 ± 0.0072, 0.012 ± 0.0069, 0.019 ± 0.0041 and 0.0062 ± 0.0007 µg ml-1 , respectively. No cross-resistance was observed between florylpicoxamid and quinone outside inhibitor (QoI), methyl benzimidazole carbamates or succinate dehydrogenase inhibitor. Florylpicoxamid also exhibited protective and curative activity against the development of B. cinerea infection in tests on tomato fruits. At application rates of 90, 112.5 and 135 g a.i. ha-1 , florylpicoxamid was also observed to provide more-effective control than boscalid (300 g a.i. ha-1 ). CONCLUSION: This study demonstrated that the novel fungicide florylpicoxamid exhibits strong inhibitory activity against B. cinerea, regardless of the resistance profiles of those isolates to tested fungicides with different modes of action. This makes florylpicoxamid a powerful new solution to optimize gray mold control and manage fungicide resistance. © 2022 Society of Chemical Industry.

Analysis of resistance risk and resistance-related point mutations in Cyt b of QioI fungicide ametoctradin in Phytophthora litchii.

BACKGROUND: Litchi downy blight, caused by Phytophthora litchii, is one of the most important diseases of litchi. Ametoctradin, as the only QioI (quinone inside and outside inhibitor) fungicide, has been registered in China in 2019. However, the ametoctradin-resistance risk and molecular basis in Phytophthora litchii have not been reported. RESULTS: In this study, the sensitivity profile of 144 Phytophthora litchii strains to ametoctradin was determined, with a mean median effective concentration (EC50 ) value of 0.1706 ± 0.091 µg mL-1 . Nine stable resistant Phytophthora litchii mutants [resistance factor (RF) > 400] were derived from sensitive isolates using fungicide adaption. The compound fitness index of three resistant-mutants (HN10-1-1, HN10-1-2 and HN10-2-1) was similar or higher than that of their parental isolates in vitro. All these ametoctradin-resistant mutants were sensitive to metalaxyl, dimethomorph, oxathiapiprolin and cyazofamid. Two point mutations, leading to the S33L and D228N changes in PlCyt b (cytochrome b) were found in ametoctradin-resistant mutants. Eight ametoctradin-resistant mutants containing S33L showed increased sensitivity to azoxystrobin and amisulbrom, and one mutant containing D228N exhibited increased sensitivity to cyazofamid. In vitro enzyme activity test showed that ametoctradin could not inhibit the activity of cytochrome bc1 complex with S33L and D228N point mutation. AS-PCR primers were designed based on the S33L change to detect the ametoctradin-resistant strains in the future. CONCLUSION: These results suggest that Phytophthora litchii has a medium to high resistance risk to ametoctradin in the laboratory. Two changes, S33L and D228N, in PlCyt b are likely to be associated with the observed ametoctradin resistance. © 2022 Society of Chemical Industry.

Structural and electrochemical corrosion studies of spin coated ZrO2 thin films over stainless steel alloy for bone defect applications.

Sol-Gel-based reaction mixture sols have been long used to fabricate dense and uniform bioactive coatings with superior mechanical stability over metallic implants. On account of precise control over synthesis, fabrication, formed and low temperature of processing, this technology is one of the most feasible routes to produce bio-ceramic coatings. The study aims to develop a physical barrier over metal implants in form of bioinert Zirconia coatings, phase-stabilized using Dysprosium. The metallic substrates were cut into 10 mm × 10 mm samples and diamond polished after being polished with a 1000 grade emery sheet. Novel spin-coated zirconia films were fabricated over 316L Stainless steel substrates and were sintered at 600°C to obtain firm and uniform crack-free coatings. The thickness of the coatings was determined by ELCA-D meter thermal analysis was performed using TGA-DTA. Phase determination was performed using X-Ray diffraction followed by morphological investigations using Scanning electron microscopy. The corrosion resistance was evaluated with Polarization studies and electrokinetic data was derived using Tafel extrapolation. Biocompatibility evaluation was performed against MG-63 cell lines and RBCs along with bone-forming ability in vitro in SBF. Stable crack-free 3 Layer coatings fabricated at 2000 rpm for 3 s with a thickness of around 1 µm were found to be optimal for corrosion resistance behavior of steel implants at a low ICorr value of 0.501 µA/cm2 and adhesion strength of 40.93 MPa when untreated falling down to 39.92 MPa when immersed in SBF. The study concludes that medium rpm coatings sustain enough sol to produce crack-free coatings that form a strong physical barrier between body fluid and implant surface thereby reducing the attack of corrosive ions and protecting the implant surface without participating in any form of bioactivity but supporting native bone regeneration capabilities.

Designing Artificial Vibration Modes of Piezoelectric Devices Using Programmable, 3D Ordered Structure with Piezoceramic Strain Units.

Piezoelectric ceramic devices, which utilize multifarious vibration modes to realize electromechanical coupling and energy conversions, are extensively used in high-technological fields. However, the excitation of basic modes is mainly subjected to natural eigenfrequency of ceramic devices, which is related to the structure and material parameters. Herein, inspired by metamaterial theory, a programmable, 3D ordered structure with piezoceramic strain units (3D OSPSU) is developed to artificially generate basic modes in a broad frequency band other than only in narrow eigenfrequency. A (2 × 2 × 2) arrayed, co-fired, multilayer 3D OSPSU is painstakingly designed and fabricated for generating basic modes, such as flexural, extension, shear, torsion, and even coupled modes at nonresonance. To validate the 3D OSPSU method, a five-degree-of-freedom micro-nano actuating platform based on only one co-fired multilayer ceramic is constructed. The proposed methodology provides a new paradigm for creating extraordinary material properties of piezoelectric ceramics and will inspire brand-new piezoelectric device designs.

Characterization of Prochloraz Resistance in Fusarium fujikuroi from Heilongjiang Province in China.

Prochloraz is widely used to control rice bakanae disease caused by Fusarium fujikuroi. The current study was aimed at monitoring the development of F. fujikuroi resistance to prochloraz in the Heilongjiang Province and analyzing the fitness of F. fujikuroi strains with different resistance levels. The results indicated that most of the 89 F. fujikuroi strains collected from the Heilongjiang Province were resistant to prochloraz, with resistance frequency reaching 92.1%. To assess the field resistance risk of prochloraz, 21 F. fujikuroi strains with different resistance levels were selected to investigate their biological characteristics and assess their fitness. Mycelial growth, sporulation, and germination rates were significantly different among the tested strains. However, when grouped into two subpopulations, no significant difference was tested between prochloraz-resistant and prochloraz-sensitive strains. Pathogenicity assays revealed that the disease severity index of prochloraz-resistant strains was higher than that of prochloraz-sensitive strains. Cross-resistance assays showed no cross-resistance between prochloraz and five other fungicides, namely phenamacril, ipconazole, tebuconazole, carbendazim, and fluopyram. Ffcyp51A gene overexpression was observed in the prochloraz-resistant F. fujikuroi strains after exposure to prochloraz. Collectively, these results indicated that F. fujikuroi resistance against prochloraz was severe. Furthermore, prochloraz-resistant strains were highly fit and could potentially become a dominant population in rice fields, consequently resulting in yield loss.

Efficient Energy-Transfer-Induced High Photoelectric Conversion in a Dye-Encapsulated Ionic Pyrene-Based Metal-Organic Framework.

The relationship between the aggregation states of pyrene-based linkers and the photoluminescence/photoelectric performance was well studied by the formation of an anionic metal-organic framework, [BMI]2[Mg3(TBAPy)2(H2O)4]·2dioxane, which shows highly enhanced light-harvesting and photoelectric conversion efficiency by the encapsulation of D-π-A cation dyes.

Tailoring Artificial Mode to Enable Cofired Integration of Shear-type Piezoelectric Devices.

Low-temperature cofired ceramic technology is the prerequisite for producing advanced integrated piezoelectric devices that enable modern micro-electromechanical systems because of merits such as high level of compactness and ultralow drive voltage. However, piezoceramic structure with shear-type outputs, as a most fundamental functional electronic element, has never been successfully fabricated into multilayer form by the cofired method for decades. Technical manufacture requirements of parallel applied electric fields and polarization are theoretically incompatible with intrinsically orthogonal orientations in naturally occurring shear modes. Herein, inspired by the philosophy of building metamaterial from identical unit cells, an artificial prototype device with distinctive patterned electrodes and arrayed piezoceramic subunits is designed and fabricated, which is proved to perfectly generate synthetic face shear deformation. At the same drive voltage, an enhanced shear-type displacement output by over an order of magnitude is observed beyond previous d15-mode bulk elements. Further results of guided wave-based structural health monitoring and force sensing confirm that the methodology wipes out a tough piezoelectric technique barrier, and promises to fundamentally enlighten advances of integrated shear-mode piezoelectric devices for augmented actuation, sensing, and transduction applications.

Designing Ordered Structure with Piezoceramic Actuation Units (OSPAU) for Generating Continual Nanostep Motion.

Continual precision actuations with nanoscale resolution over large ranges have extensive requirements in advanced intelligent manufacturing and precise surgical robots. To produce continual nanostep motion, conventionally, multiple pairs of piezo-actuators are employed to operate in inchworm principle under complex three- or four-phase timing signal drive. Inspired by the idea of ordered structures with functional units, a much simpler nanostep piezoelectric actuator consisting of (2 × 2) arrayed, cofired multilayer piezoceramic actuation units is developed, which operates in an artificially generated quasi shear mode (AGQSM) that is missing in natural piezoelectric ceramics. Under only one-phase square-wave voltage drive, the actuator can produce a stable, continual nanostep motion in two ways at nonresonant frequencies, and the obtained minimum step displacement is as low as 7 nm in open control, indicating its potential application as a precise finger or knife actuator in surgical robots. This work is of great guiding significance for future actuator designs using the methodology of ordered structure with piezoceramic actuation units and AGQSM.

A Piezoelectric and Electromagnetic Dual Mechanism Multimodal Linear Actuator for Generating Macro- and Nanomotion.

Fast actuation with nanoprecision over a large range has been a challenge in advanced intelligent manufacturing like lithography mask aligner. Traditional stacked stage method works effectively only in a local, limited range, and vibration coupling is also challenging. Here, we design a dual mechanism multimodal linear actuator (DMMLA) consisted of piezoelectric and electromagnetic costator and coslider for producing macro-, micro-, and nanomotion, respectively. A DMMLA prototype is fabricated, and each working mode is validated separately, confirming its fast motion (0~50 mm/s) in macromotion mode, micromotion (0~135 µm/s) and nanomotion (minimum step: 0~2 nm) in piezoelectric step and servomotion modes. The proposed dual mechanism design and multimodal motion method pave the way for next generation high-precision actuator development.

Designing electromechanical metamaterial with full nonzero piezoelectric coefficients.

Designing topological and geometrical structures with extended unnatural parameters (negative, near-zero, ultrahigh, or tunable) and counterintuitive properties is a big challenge in the field of metamaterials, especially for relatively unexplored materials with multiphysics coupling effects. For natural piezoelectric ceramics, only five nonzero elements in the piezoelectric matrix exist, which has impeded the design and application of piezoelectric devices for decades. Here, we introduce a methodology, inspired by quasi-symmetry breaking, realizing artificial anisotropy by metamaterial design to excite all the nonzero elements in contrast to zero values in natural materials. By elaborately programming topological structures and geometrical dimensions of the unit elements, we demonstrate, theoretically and experimentally, that tunable nonzero or ultrahigh values of overall effective piezoelectric coefficients can be obtained. While this work focuses on generating piezoelectric parameters of ceramics, the design principle should be inspirational to create unnatural apparent properties of other multiphysics coupling metamaterials.

Enhanced Resonance Magnetoelectric Coupling in (1-1) Connectivity Composites.

Bulk-magnetoelectric (ME) composites consisting of various piezoelectric and piezomagnetic materials with (3-0), (3-1), (2-2), and (2-1) connectivity are proposed in a bid to realize strong ME coupling for next-generation electronic-device applications. Here, 1D (1-1) connectivity ME composites consisting of a [011]-oriented Pb(Mg,Nb)O3 -PbTiO3 (PMN-PT) single-crystal fiber laminated with laser-treated amorphous FeBSi alloy (Metglas) and operating in L-T mode (longitudinally magnetized and transversely poled) are reported, which exhibit an enhanced resonant ME coupling coefficient of ≈7000 V cm-1  Oe-1 , which is nearly seven times higher than the best result published previously, and also a superhigh magnetic sensitivity of 1.35 × 10-13 T (directly detected) at resonance at room temperature, representing a significant advance in bulk magnetoelectric materials. The theoretical analyses based on magnetic-circuit and equivalent-circuit methods show that the enhancement in ME coupling can be attributed to the reduction in resonance loss of laser-treated Metglas alloy due to nanocrystallization and the strong magnetic-flux-concentration effect in (1-1) configuration composites.

Tanshinol sustained-release pellets with absorption enhancer: optimization, characterization, pharmacokinetics and pharmacodynamics.

The objective of this study was to develop tanshinol sustained-release pellets (TS-SRPs) for the treatment of angina. Considering the poor intestinal absorption of TS, sodium caprate (SC) was used as an absorption enhancer for bioavailability improvement. Single-pass intestinal perfusion in rats demonstrated that the permeability of TS was remarkably enhanced, when the weight ratio of TS to SC was 1:3. Then, the cores were prepared with TS, SC and MCC at a weight ratio of 1:3:16 via extrusion-spheronization, followed by coating with Eudragit® RS30D/RL30D dispersion (9:1, w/w). In vitro release studies revealed that release methods and rotation rates had no significant effects on the drug release of optimized TS-SC-SRPs except for the dissolution media. The release behavior was characterized as non-Fick diffusion mechanism. The pellets possessed a dispersion-layered spherical structure and were stable during three months of storage at 40 °C/75% RH. Compared with TS immediate-release pellets, the AUC0-24 in healthy rabbits was increased by 1.97-fold with prolonged MRT (p < .05). Pharmacodynamic studies in rabbits with angina showed that the optimized TS-SC-SRPs had a steady and improved efficacy with synchronous drug concentration-efficacy. Consequently, preparation of sustained-release pellets with absorption enhancer provides a potential strategy to prolong the release and enhance the efficacy for hydrophilic drugs with poor intestinal absorption.

Bioavailability and foam cells permeability enhancement of Salvianolic acid B pellets based on drug-phospholipids complex technique.

This study investigated phospholipids complex (PC) loaded pellets of poorly permeable Salvianolic acid B (SalB), in which PC was to improve the liposolubility and permeability of SalB. Transmission electron microscopy observation, differential scanning calorimetry measurement, infrared spectroscopy analysis, n-octanol/water partition coefficient study, and foam cell permeability research were employed to prove the complex formation. Pellets containing SalB phospholipids complex (SalB-PC) were prepared via extrusion/spheronization technique. The optimal pellets obtained with 30% SalB-PC, 15% Kollidon®CL-SF, 15% Flowlac®100, and 40% MCC exhibited a very homogeneous size distribution, the shortest disintegration time, highest crushing force, appreciable spherical shape, and a fast drug release behavior. Following hydration, the droplet size distribution of SalB-PC pellets was nearly same to its PC (85.4±16 and 73.5±12nm). In vivo performance showed SalB-PC pellets presented significantly larger AUC(0-)(t), which was 0.58 times more than that of physical mixtures (PMs) and 1.57 times more than that of SalB pellets. C(max) of SalB-PC pellets were also increased by 0.26-fold and 0.80-fold as that of PMs and SalB pellets, respectively. In conclusion, extrusion/spheronization could be a suitable technique to prepare PC loaded pellets, which could effectively preserve the properties of PC to improve the permeability and bioavailability of highly water-soluble drug.

Release behavior of tanshinone IIA sustained-release pellets based on crack formation theory.

The objective of this study was to investigate the drug release mechanism and in vivo performance of Tanshinone IIA sustained-release pellets, coated with blends of polyvinyl acetate (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A formulation screening study showed that pellets coated with PVAc-PVA-PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24 h sustained release, irrespective of the coating weight (from 2% to 10%). Both the microscopic observation and mathematical model gave further insight into the underlying release mechanism, indicating that diffusion through water-filled cracks was dominant for the control of drug release. In vivo test showed that the maximum plasma concentration of sustained-release pellets was decreased from 82.13 ± 17.05 to 40.50 ± 11.72 ng mL as that of quick-release pellets. The time of maximum concentration, half time, and mean residence time were all prolonged from 3.80 ± 0.40 to 8.02 ± 0.81 h, 4.28 ± 1.21 to 8.18 ± 2.06 h, and 8.60 ± 1.59 to 17.50 ± 2.78 h, compared with uncoated preparations. A good in vitro-in vivo correlation was characterized by a high coefficient of determination (r = 0.9772). In conclusion, pellets coated with PVAc-PVA-PEG could achieve a satisfactory sustained-release behavior based on crack formation theory.