Deciphering the Transcriptional Regulatory Network Governing Starch and Storage Protein Biosynthesis in Wheat for Breeding Improvement.

Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis, transcriptome, and epigenome profiling is conducted across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlight accessible promoter regions' crucial role as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. Integration of time-serial RNA-seq and ATAC-seq enables the construction of a hierarchical transcriptional regulatory network governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibit overlap with genetic regions associated with grain size and quality traits, and their functional significance is validated through expression-phenotype association analysis among wheat accessions and loss-of-function mutants. Functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrates its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. Excellent TaABI3-A1Hap1 with enhanced grain weight is selected during the breeding process in China, linked to altered expression levels. This study unveils key regulators, advancing understanding of SSP and starch biosynthesis regulation and contributing to breeding enhancement.

Radiation Patterns of RF Wireless Devices Implanted in Small Animals: Unexpected Deformations Due to Body Resonance.

One challenge in designing RF wireless bioelectronic devices is the impact of the interaction between electromagnetic waves and host body tissues on far-field wireless performance. In this article, we investigate a peculiar phenomenon of implantable RF wireless devices within a small-scale host body related to the deformation of the directivity pattern. Radiation measurements of subcutaneously implanted antennas within rodent cadavers show that the direction of maximum radiation is not always identical with the direction to the closest body-air interface, as one would expect in larger-scale host bodies. For an implanted antenna in the back of a mouse, we observed the maximum directivity in the ventral direction with 4.6 dB greater gain compared to the nearest body-air interface direction. Analytic analysis within small-scale spherical body phantoms identifies two main factors for these results: the limited absorption losses due to the small body size relative to the operating wavelength and the high permittivity of the biological tissues of the host body. Due to these effects, the entire body acts as a dielectric resonator antenna, leading to deformations of the directivity pattern. These results are confirmed with the practical example of a wirelessly powered 2.4-GHz optogenetic implant, demonstrating the significance of the judicious placement of external antennas to take advantage of the deformation of the implanted antenna pattern. These findings emphasize the importance of carefully designing implantable RF wireless devices based on their placements and relative electrical dimensions in small-scale animal models.

A modularized high-power ultra-wideband radiation system based on the space-synthesis method.

In this paper, a high-power ultra-wideband radiation system, composed of multiply radiation modules, is developed based on the space-synthesis method. The radiation module mainly consists of a transistorized pulser, a 2 × 2 combined antenna array, and a power divider. To improve the out parameters [the amplitude, the pulse repetition frequency (PRF), and the rise time] of the transistorized pulser based on the Marx circuit, the influence of the traveling wave process on the output pulse must be concerned. Based on the theoretical analysis, the printed circuit board circuit parameters and the circuit structure of the pulser are optimized. To improve the power synthesis efficiency, the pulse jitter characteristic of the pulser is improved by replacing the conventional base triggering mode with the collector voltage ramp triggering mode for the first-stage avalanche transistor in the pulser. The previous optimized antenna array is utilized in this radiation system, which has a better radiation performance in the prescribed aperture area. In addition, based on the gradient microstrip structure, the power divider integrated with the pulser is designed, which has the advantages of wide bandwidth, low loss, and light weight. Experimental results show that the peak effective potential rEp of the radiation system of 20 radiation modules is 221.8 kV, the maximum PRF could reach 10 kHz, and the half-power radiation angles of its radiation field are about 5° in both the E plane and the H plane. More radiation modules could be integrated into the system to achieve a higher electric field in the future.

Cdc25C/cdc2/cyclin B, raf/MEK/ERK and PERK/eIF2α/CHOP pathways are involved in forskolin-induced growth inhibition of MM.1S cells by G2/M arrest and mitochondrion-dependent apoptosis.

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM.

A wideband picosecond pulsed electric fields (psPEF) exposure system for the nanoporation of biological cells.

The effects and mechanisms of ultrashort and intense pulsed electric fields on biological cells remain some unknown. Especially for picosecond pulsed electric fields (psPEF) with a high pulse repetition rate, electroporation or nanoporation effects could be induced on cell membranes and intracellular organelle membranes. In this work, the design, implementation, and experimental validation of a wideband psPEF exposure system (WPES) is reported, comprising picosecond pulser and wideband biochip, for the in vitro exposure of suspended cells to high-intensity psPEF. Excited by repetitive picosecond pulses (the duration of 200 ps and the amplitude of a few kilovolts), the proposed biochip adopts grounded coplanar waveguide (GCPW) for a wide working bandwidth, which was fabricated with 160 µm thick electrodes for uniform distribution of psPEF in the cross-section. To ensure that only psPEF is generated in the biological medium containing cells except for ionic current, this work proposes to install capillary tubes in the electrode gaps for electrical insulation and cells delivery. By electrical measurements in the time domain and frequency domain, the exposure system is adapted for local generation of extremely high-intensity psPEF with the 3 dB bandwidth up to 4.2 GHz. Furthermore, biological experiments conducted on the developed exposure system verified its capability to permeabilize biological cells under the exposure of high-intensity psPEF.

Assessment of the anti-virulence potential of extracts from four plants used in traditional Chinese medicine against multidrug-resistant pathogens.

BACKGROUND: Multidrug-resistant pathogens are resistant to many antibiotics and associated with serious infections. Amomum tsaoko Crevost et Lemaire, Sanguisorba officinalis, Terminalia chebula Retz and Salvia miltiorrhiza Bge, are all used in Traditional Chinese Medicine (TCM) against multidrug-resistant pathogens, and the purpose of this study was to evaluate the antibacterial and anti-virulence activity of extracts derived from them. METHODS: The antibacterial activity of ethanol and aqueous extracts from these four plants was examined against several multi-drug resistant bacterial strains, and their anti-virulence potential (including quorum quenching activity, biofilm inhibition, and blocking production of virulence factor δ-toxin) was assessed against different S. aureus strains. The chemical composition of the most effective extract was determined by LC-FTMS. RESULTS: Only extracts from S. officinalis and A. tsaoko were shown to exhibit limited growth inhibition activity at a dose of 256 µg·mL-1. The S. officinalis ethanol extract, the ethanol and aqueous extract of A. tsaoko, and the aqueous extract of S. miltiorrhiza all demonstrated quorum quenching activity, but didn't significantly inhibit bacterial growth. The ethanol extract of S. officinalis inhibited bacterial toxin production and biofilm formation at low concentrations. Chemical composition analysis of the most effective extract of S. officinalis showed that it mainly contained saponins. CONCLUSIONS: The most active extract tested in this study was the ethanol root extract of S. officinalis. It inhibited δ-toxin production and biofilm formation at low concentrations and saponins may be its key active components. While the four plants showed no direct antibacterial effects, their anti-virulence properties may be key to fighting bacterial infections.

High power and high pulse repetition frequency transistorized pulser by time base stability improvement and power synthesis technique.

Output power of a transistorized pulser is usually limited by the power capacity of avalanche transistors. To improve the total output power, the power synthesis method is widely used, in which a single pulser with high output power and high time base stability is required. However, the time base stability tends to deteriorate as the output power increases. To improve the output power under the premise of high time base stability, from the perspective of carrier movement, the mechanisms of pulse jitter and pulse drift are investigated. It is found that the pulse jitter is caused by time dispersion of the ionization process in the collector depletion region, while the pulse drift is due to the decrement of the diffusion coefficient Dn and the electron mobility µn, which are both temperature-dependent. Based on the microscopic theoretical study, some macroscopic improvements on the time base stability are made. Some parameters of the trigger pulse and the circuit (e.g., charging capacitance) are optimized experimentally. Consequently, we achieved a pulser with an amplitude of 1.8 kV, pulse jitter of 25 ps, pulse drift of 100 ps/min at a pulse repetition frequency (PRF) of 100 kHz. Additionally, a new parameter k, the product of the highest PRF f and the peak power Ep, is defined to evaluate the output power. With almost the same time base stability, the proposed pulser has a k of 6.48 GHz W, which is improved significantly. Finally, a synthesized pulser with an amplitude of 2.5 kV and highest PRF of 100 kHz is achieved.

A portable ultrawideband electromagnetic radiator with a 1.4 MW/50 kHz solid-state subnanosecond pulser.

In this note, a portable ultrawideband (UWB) electromagnetic radiator is developed based on a transistorized pulser with the peak power of 1.4 MW, the rise time less than 150 ps, and the repetition frequency of 50 kHz. To generate high-amplitude pulses, a 100-stage Marx circuit with parallel connection of multiple transistors is proposed. To improve the pulse repetition rate, the parallel charging Marx circuit is adopted with ferrite beads connected in series between stages for high isolation of pulses. In order to radiate the UWB electromagnetic pulse directionally, a compact combined antenna array is fabricated and connected with the pulser via a coaxial feeding module. The effective potential of the UWB radiator reaches 10.5 kV with the band range (-10 dB) from 173 MHz to 2.32 GHz.

Design, synthesis and biological evaluation of N1-(isoquinolin-5-yl)-N2-phenylpyrrolidine-1,2-dicarboxamide derivatives as potent TRPV1 antagonists.

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on a N1-(isoquinolin-5-yl)-N2-phenylpyrrolidine-1,2-dicarboxamide platform that evolved from a 5-aminoisoquinoline urea lead. Advancing the SAR of this series led to the eventual identification of 3b, comprising a p-Br substituted phenyl. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 3b displayed potent antagonism activated by capsaicin (IC50 = 0.084 µM) and protons (IC50 = 0.313 µM). In the preliminary analgesic and body temperature tests, 3b exhibited good efficacy in capsaicin-induced and heat-induced pain models and without hyperthermia side-effect. On the basis of its superior profiles, 3b could be considered as the lead candidate for the further development of antinociceptive drugs.

Effect of Selective Laser Melting Process Parameters on Microstructure and Properties of Co-Cr Alloy.

Due to the rapid melting and solidification mechanisms involved in selective laser melting (SLM), CoCrMo alloys fabricated by SLM differ from the cast form of the same alloy. In this study, the relationship between process parameters and the morphology and macromechanical properties of cobalt-chromium alloy micro-melting pools is discussed. By measuring the width and depth of the molten pool, a theoretical model of the molten pool is established, and the relationship between the laser power, the scanning speed, the scanning line spacing, and the morphology of the molten pool is determined. At the same time, this study discusses the relationship between laser energy and molding rate. Based on the above research, the optimal process for the laser melting of cobalt-chromium alloy in the selected area is obtained. These results will contribute to the development of biomedical CoCr alloys manufactured by SLM.

Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H2S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H2S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B9, containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H2S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H2S-releasing capability.