Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both ...broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.
Chemical modification of antimicrobial peptides augments their antibacterial action
via
multiple mechanisms.
Robust and centimeter-level Real-time Kinematic (RTK)-based Global Navigation Satellite System (GNSS) positioning is of paramount importance for emerging GNSS applications, such as drones and ...automobile systems. However, the performance of conventional single-rover RTK degrades greatly in urban environments due to signal blockage and strong multipath. The increasing use of multiple-antenna/rover configurations for attitude determination in the above precise positioning applications, just as well, allows more information involved to improve RTK positioning performance in urban areas. This paper proposes a dual-antenna constraint RTK algorithm, which combines GNSS measurements of both antennas by making use of the geometric constraint between them. By doing this, the reception diversity between two antennas can be taken advantage of to improve the availability and geometric distribution of GNSS satellites, and what is more, the redundant measurements from a second antenna help to weaken the multipath effect on the first antenna. Particularly, an Ambiguity Dilution of Precision (ADOP)-based analysis is carried out to explore the intrinsic model strength for ambiguity resolution (AR) with different kinds of constraints. Based on the results, a Dual-Antenna with baseline VEctor Constraint algorithm (RTK) is developed. The primary advantages of the reported method include: 1) Improved availability and success rate of RTK, even if neither of the two single-antenna receivers can successfully solve the AR problem; and 2) reduced computational burden by adopting the concept of measurement projection. Simulated and real data experiments are performed to demonstrate robustness and precision of the algorithm in GNSS-challenged environments.
With the increasing proportion of wind turbines in power grids, they are required to have capabilities of active and efficient virtual inertial response to maintain grid frequency stability. However, ...the virtual inertial control methods currently used in doubly-fed induction generator (DFIG) units suffer from a secondary frequency drop (SFD) problem. Although the SFD can be inhibited by reducing the active power support strength of the DFIG units during inertia response, it will undoubtedly weaken the virtual inertia of the units. Therefore, how to eliminate the SFD while increasing the virtual inertia of the units is a worthy issue for studying. To solve this issue, a wind-storage combined virtual inertial control system based on quantization and regulation decoupling of active power increments is proposed in this paper. First, by setting the parameters of a proportional–differential (P-D) algorithm, the total active power increments required for virtual inertial response are quantified at the DFIG level. Secondly, a curve-shifting method based on the rate of change of frequency is adopted to adjust the active power output of the DFIG units. Finally, a battery energy storage system (BESS) is used to compensate for the power shortages of the units according to the quantized value of the active power increments. Simulations show that the control method can not only eliminate SFD but also effectively increase the system’s virtual inertia.
Post-harvest rot causes enormous economic loss to the global kiwifruit industry. Currently, there are no effective fungicides to combat the disease. It is unclear whether silver nanoparticles (AgNPs) ...are effective in controlling post-harvest rot and, if so, what the underlying antifungal mechanism is. Our results indicated that 75 ppm AgNPs effectively inhibited the mycelial growth and spore germination of four kiwifruit rot pathogens:
Alternaria alternata
,
Pestalotiopsis microspora
,
Diaporthe actinidiae
, and
Botryosphaeria dothidea
. Additionally, AgNPs increased the permeability of mycelium’s cell membrane, indicating the leakage of intracellular substance. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations revealed that AgNPs induced pathogen hypha shrinkage and distortion, as well as vacuolation in hypha cells, implying that AgNPs caused cellular and organelle structural degradation. The transcriptome sequencing of mycelium treated with AgNPs (24 h / 48 h) was performed on the Illumina Hiseq 4000 sequencing (RNA-Seq) platform. For the time points of 24 h and 48 h, AgNPs treatment resulted in 1,178 and 1,461 differentially expressed genes (DEGs) of
A. alternata
, 517 and 91 DEGs of
P. microspora
, 1,287 and 65 DEGs of
D. actinidiae
, 239 and 55 DEGs of
B. dothidea
, respectively. The DEGs were found to be involved in “catalytic activity,” “small molecule binding,” “metal ion binding,” “transporter activity,” “cellular component organization,” “protein metabolic process,” “carbohydrate metabolic process,” and “establishment of localization.” Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis also revealed that “carbohydrate metabolism,” “amino acid metabolism,” “energy metabolism,” and “xenobiotics biodegradation and metabolism” of “metabolism processes” were the most highly enriched pathways for these DEGs in four pathogens, with “cellular processes” being particularly enriched for
B. dothidea.
Furthermore, quantitative polymerase chain reactions (qPCRs) were used to validate the RNA-seq results. It was also confirmed that AgNPs could significantly reduce the symptoms of kiwifruit rot without leaving any Ag
+
residue on the peel and flesh of kiwifruit. Our findings contributed to a better understanding of the antifungal effect and molecular mechanisms of AgNPs against pathogens causing kiwifruit post-harvest rot, as well as a new perspective on the application of this novel antifungal alternative to fruit disease control.
The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved ...mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two‐phase systems are utilized to generate programmable hydrogel ionic circuits. High‐conductivity salt‐solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous‐based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light‐emitting diode (LED)‐based displays, skin‐mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems.
Programmable hydrogel ionic circuits completely composed of salt, water, and biofriendly hydrogels are developed based on salt/poly(ethylene glycol) aqueous two‐phase systems. Such systems enable designer electronics that match the properties of biological systems and route high‐resolution ionic electrical signals between engineered and living systems while avoiding tissue damage. Such platforms may form the basis of future biointegrated electronic systems.
Natural systems display sophisticated control of light-matter interactions at multiple length scales for light harvesting, manipulation, and management, through elaborate photonic architectures and ...responsive material formats. Here, we combine programmable photonic function with elastomeric material composites to generate optomechanical actuators that display controllable and tunable actuation as well as complex deformation in response to simple light illumination. The ability to topographically control photonic bandgaps allows programmable actuation of the elastomeric substrate in response to illumination. Complex three-dimensional configurations, programmable motion patterns, and phototropic movement where the material moves in response to the motion of a light source are presented. A "photonic sunflower" demonstrator device consisting of a light-tracking solar cell is also illustrated to demonstrate the utility of the material composite. The strategy presented here provides new opportunities for the future development of intelligent optomechanical systems that move with light on demand.
The self-noise level of a seismometer can determine the performance of the seismic instrument and limit the ability to use seismic data to solve geoscience problems. Accurately measuring and ...simultaneously comparing the self-noise models from different types of seismometers has long been a challenging task due to the constraints of observation conditions. In this paper, the self-noise power spectral density (PSD) values of nine types of seismometers are calculated using four months of continuous seismic waveforms from Malingshan seismic station, China, and nine self-noise models are obtained based on the probability density function (PDF) representation. For the seismometer STS-2.5, the self-noise levels on the horizontal channels (E−W and N−S) are significantly higher than that on the vertical channel (U−D) in the microseism band (0.1 Hz to 1 Hz), which is a computing bias caused by the misalignment between the sensors in the horizontal direction, while the remarkably elevated noise on the horizontal channels at the low frequencies (<0.6 Hz) may originate from the local variation of atmospheric pressure. As for the very broadband seismometers Trillium-Horizon-120 and Trillium-120PA, and the ultra-broadband seismometers Trillium-Horizon-360 and CMG-3T-360, there is a trade-off between the microseism band range and low-frequency range in the PSD curves of the vertical channel. When the level of self-noise in the microseism band is high, the self-noise at low frequencies is relatively low. Although compared with the other very broadband seismometers, the self-noise level of the vertical component of the STS-2.5 is 3 dB to 4 dB lower at frequencies less than 1 Hz, the self-noise level of the STS-2.5 at high frequencies (>2 Hz) is slightly higher than others. From our observations, we conclude that the nine seismometers cannot reach the lowest noise level in all frequency bands within the working range.
Abstract This study intends to inspect the effects of acute aerobic exercise (AE) on resting state functional connectivity (RSFC) in motor cortex of college students and the moderating effect of ...fitness level. Methods: 20 high fitness level college students and 20 ordinary college students were recruited in public. Subjects completed 25 min of moderate- and high-intensity acute aerobic exercise respectively by a bicycle ergometer, and the motor cortex’s blood oxygen signals in resting state were monitored by functional Near Infrared Spectroscopy (fNIRS, the Shimadzu portable Light NIRS, Japan) in pre- and post-test. Results: At the moderate intensity level, the total mean value of RSFC pre- and post-test was significantly different in the high fitness level group (pre-test 0.62 ± 0.18, post-test 0.51 ± 0.17, t (19) = 2.61, p = 0.02, d = 0.58), but no significant change was found in the low fitness level group. At the high-intensity level, there was no significant difference in the difference of total RSFC between pre- and post-test in the high and low fitness group. According to and change trend of 190 “edges”: at the moderate-intensity level, the number of difference edges in the high fitness group ( d = 0.58, 23) were significantly higher than those in the low fitness group ( d = 0.32, 15), while at high-intensity level, there was a reverse trend between the high fitness group ( d = 0.25, 18) and the low fitness group ( d = 0.39, 23). Conclusions: moderate-intensity AE can cause significant changes of RSFC in the motor cortex of college students with high fitness, while high fitness has a moderating effect on the relationship between exercise intensity and RSFC. RSFC of people with high fitness is more likely to be affected by AE and show a wider range of changes.
With the development of power modules for high voltage, high temperature, and high power density, their size is becoming smaller, and the packaging insulation experiences higher electrical, thermal, ...and mechanical stress. Packaging insulation needs to meet the requirement that internal electric field, temperature, and mechanical stress should be as low as possible. Focusing on the coupling principles and optimization design among electrical, thermal, and mechanical stresses in the power module packaging insulation, a multi-objective optimization design method based on Spice circuit, finite element field numerical calculation, and multi-objective gray wolf optimizer (MOGWO) is proposed. The packaging insulation optimal design of a 1.2 kV SiC MOSFET half-bridge power module is presented. First, the high field conductivity characteristics of the substrate ceramic and encapsulation silicone of the packaging insulation material were tested at different temperatures and external field strengths, which provided the key insulation parameters for the calculation of electric field distribution. Secondly, according to the mutual coupling principles among electric–thermal–mechanical stress, the influence of packaging structure parameters on the electric field, temperature, and mechanical stress distribution of packaging insulation was studied by finite element calculation and combined with Spice circuit analysis. Finally, the MOGWO algorithm was used to optimize the electric field, temperature, and mechanical stress in the packaging insulation. The optimal structural parameters of the power module were used to fabricate the corresponding SiC MOSFET module. The fabricated module is compared with a commercial module by the double-pulse experiment and partial discharge experiment to verify the feasibility of the proposed design method.
The tumor microenvironment (TME) is known to have a strong influence on tumorigenesis, with various components being involved in tumor suppression and tumor growth. A protumorigenic TME is ...characterized by an increased infiltration of tumor associated macrophages (TAMs), where their presence is strongly associated with tumor progression, therapy resistance, and poor survival rates. This association between the increased TAMs and poor therapeutic outcomes are stemming an increasing interest in investigating TAMs as a potential therapeutic target in cancer treatment. Prominent mechanisms in targeting TAMs include: blocking recruitment, stimulating repolarization, and depletion methods. For enhancing targeting specificity multiple nanomaterials are currently being explored for the precise delivery of chemotherapeutic cargo, including the conjugation with TAM-targeting peptides. In this paper, we provide a focused literature review of macrophage biology in relation to their role in tumorigenesis. First, we discuss the origin, recruitment mechanisms, and phenotypic diversity of TAMs based on recent investigations in the literature. Then the paper provides a detailed review on the current methods of targeting TAMs, including the use of nanomaterials as novel cancer therapeutics.
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