Identification and functional characterization of ABC transporters for selenium accumulation and tolerance in soybean.

ATP-binding cassette (ABC) transporters were crucial for various physiological processes like nutrition, development, and environmental interactions. Selenium (Se) is an essential micronutrient for humans, and its role in plants depends on applied dosage. ABC transporters are considered to participate in Se translocation in plants, but detailed studies in soybean are still lacking. We identified 196 ABC genes in soybean transcriptome under Se exposure using next-generation sequencing and single-molecule real-time sequencing technology. These proteins fell into eight subfamilies: 8 GmABCA, 51 GmABCB, 39 GmABCC, 5 GmABCD, 1 GmABCE, 10 GmABCF, 74 GmABCG, and 8 GmABCI, with amino acid length 121-3022 aa, molecular weight 13.50-341.04 kDa, and isoelectric point 4.06-9.82. We predicted a total of 15 motifs, some of which were specific to certain subfamilies (especially GmABCB, GmABCC, and GmABCG). We also found predicted alternative splicing in GmABCs: 60 events in selenium nanoparticles (SeNPs)-treated, 37 in sodium selenite (Na2SeO3)-treated samples. The GmABC genes showed differential expression in leaves and roots under different application of Se species and Se levels, most of which are belonged to GmABCB, GmABCC, and GmABCG subfamilies with functions in auxin transport, barrier formation, and detoxification. Protein-protein interaction and weighted gene co-expression network analysis suggested functional gene networks with hub ABC genes, contributing to our understanding of their biological functions. Our results illuminate the contributions of GmABC genes to Se accumulation and tolerance in soybean and provide insight for a better understanding of their roles in soybean as well as in other plants.

Mirror Symmetry Broken of Sound Vortex Transmission in a Single Passive Metasurface via Phase Coupling.

Asymmetric transmission in a passive vortex system is highly desirable, as it enables the development of compact vortex-based devices. However, breaking the mirror symmetry of transmission via a single metasurface poses challenges due to the inherent symmetric transmission properties in reciprocity. Here, we theoretically propose and experimentally demonstrate a novel transmission-reflection phase coupling mechanism to achieve the broken mirror symmetry of sound vortex transmission. This mechanism establishes a special coupling link between transmission and reflection waves, superimposing asymmetric reflection phases on the transmission phases. By utilizing a single passive phase gradient metasurface with asymmetric reflection phase twists, distinct transmission phase twists for mirror-symmetric incident vortices can be achieved within a cylindrical waveguide. This is typically difficult to imple-ment in a reciprocal system. Numerical and experimental results both demonstrate the broken mirror symmetry of vortex transmission and reflection. Our findings offer a new strategy for controlling vortex wave propagation, which may inspire new directional applications and extend to the field of photonics.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Extracting Stress-Related EEG Patterns From Pre-Sleep EEG for Forecasting Slow-Wave Sleep Deficiency.

Sleep is vital to our daily activity. Lack of proper sleep can impair functionality and overall health. While stress is known for its detrimental impact on sleep quality, the precise effect of pre-sleep stress on subsequent sleep structure remains unknown. This study introduced a novel approach to study the pre-sleep stress effect on sleep structure, specifically slow-wave sleep (SWS) deficiency. To achieve this, we selected forehead resting EEG immediately before and upon sleep onset to extract stress-related neurological markers through power spectra and entropy analysis. These markers include beta/delta correlation, alpha asymmetry, fuzzy entropy (FuzzEn) and spectral entropy (SpEn). Fifteen subjects were included in this study. Our results showed that subjects lacking SWS often exhibited signs of stress in EEG, such as an increased beta/delta correlation, higher alpha asymmetry, and increased FuzzEn in frontal EEG. Conversely, individuals with ample SWS displayed a weak beta/delta correlation and reduced FuzzEn. Finally, we employed several supervised learning models and found that the selected neurological markers can predict subsequent SWS deficiency. Our investigation demonstrated that the classifiers could effectively predict varying levels of slow-wave sleep (SWS) from pre-sleep EEG segments, achieving a mean balanced accuracy surpassing 0.75. The SMOTE-Tomek resampling method could improve the performance to 0.77. This study suggests that stress-related neurological markers derived from pre-sleep EEG can effectively predict SWS deficiency. Such information can be integrated with existing sleep-improving techniques to provide a personalized sleep forecasting and improvement solution.

Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti-cardiac fibrosis activity.

Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW-7197 (vactosertib) and 14 times that of the clinical candidate LY-2157299. The selectivity index of 16f against p38α mitogen-activated protein kinase was >109, which was much higher than that of positive controls (EW-7197: >41, and LY-2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α-smooth muscle actin (α-SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP-1)/matrix metalloproteinase 13 (MMP-13) in transforming growth factor-ß-induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.

In Situ Fabrication of Silver Nanoparticle-Decorated Polymeric Vesicles for Antibacterial Applications.

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) for the produced AgNP-decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP-decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 µg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP-decorated vesicles.

Two B-box proteins orchestrate vegetative and reproductive growth in summer chrysanthemum.

Floral transition, the switch from vegetative to reproductive growth, is extremely important for the growth and development of flowering plants. In the summer chrysanthemum, CmBBX8, a member of the subgroup II B-box (BBX) family, positively regulates the transition by physically interacting with CmERF3 to inhibit CmFTL1 expression. In this study, we show that CmBBX5, a B-box subgroup I member comprising two B-boxes and a CCT domain, interacts with CmBBX8. This interaction suppresses the recruitment of CmBBX8 to the CmFTL1 locus without affecting its transcriptional activation activity. CmBBX5 overexpression led to delayed flowering under both LD (long-day) and SD (short-day) conditions, while lines expressing the chimeric repressor gene-silencing (CmBBX5-SRDX) exhibited the opposite phenotype. Subsequent genetic evidence indicated that in regulating flowering, CmBBX5 is partially dependent on CmBBX8. Moreover, during the vegetative growth period, levels of CmBBX5 expression were found to exceed those of CmBBX8. Collectively, our findings indicate that both CmERF3 and CmBBX5 interact with CmBBX8 to dampen the regulation of CmFTL1 via distinct mechanisms, which contribute to preventing the premature flowering of summer chrysanthemum.

Polarization-insensitive high-numerical-aperture metalens for wide-field super-resolution imaging.

The development of super-oscillatory lens (SOL) offers opportunities to realize far-field label-free super-resolution microscopy. Most microscopes based on a high numerical aperture (NA) SOL operate in the point-by-point scanning mode, resulting in a slow imaging speed. Here, we propose a high-NA metalens operating in the single-shot wide-field mode to achieve real-time super-resolution imaging. An optimization model based on the exhaustion algorithm and angular spectrum (AS) theory is developed for metalens design. We numerically demonstrate that the optimized metalens with an NA of 0.8 realizes the imaging resolution (imaging pixel size) about 0.85 times the Rayleigh criterion. The metalens can achieve super-resolution imaging of an object with over 200 pixels, which is one order of magnitude higher than the unoptimized metalens. Our method provides an avenue toward single-shot far-field label-free super-resolution imaging for applications such as real-time imaging of living cells and temporally moving particles.

Application of 18ß-glycyrrhetinic acid in the structural modification of natural products: a review.

18ß-Glycyrrhetinic acid (GA) is an oleane-type pentacyclic triterpene saponin obtained from glycyrrhizic acid by removing 2 glucuronic acid groups. GA and its analogues are active substances of glycyrrhiza aicd, with similar structure and important pharmacological effects such as anti-inflammatory, anti-diabetes, anti-tumor and anti-fibrosis. Although GA combined compounds are in the clinical trial stages, its application potential is severely restricted by its low bioavailability, water solubility and membrane permeability. In this article, synthetic methods and structure-activity relationships (SARs) of GA derivatives from 2018 to present are reviewed based on pharmacological activity. It is hoped that this review can provide reference for the future development of potential GA preclinical candidate compounds, and furnish ideas for the development of pentacyclic triterpenoid lead compounds.

Oxalisxishuiensis (Oxalidaceae), a new species from Danxia landforms in Guizhou, China.

Oxalisxishuiensis, a new species of Oxalidaceae from Danxia landforms of Xishui County, Guizhou, China, is described and illustrated. It is morphologically similar to O.wulingensis by the two lateral leaflets arranged at about 180° angle and oblong pink petals with lilac veins, but clearly differs from the latter by leaflets almost as long as wide, obliquely obcordate lateral leaflets, shorter peduncles, longer capsule (1.2-1.5 cm vs. 0.5-0.7 cm) and alveolate seeds.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Rational engineering S1' substrate binding pocket to enhance substrate specificity and catalytic activity of thermal-stable keratinase for efficient keratin degradation.

This study reports the rational engineering of the S1' substrate-binding pocket of a thermally-stable keratinase from Pseudomonas aeruginosa 4-3 (4-3Ker) to improve substrate specificity to typical keratinase (K/C > 0.5) and catalytic activity without compromising thermal stability for efficient keratin degradation. Of 10 chosen mutation hotspots in the S1' substrate-binding pocket, the top three mutations M128R, A138V, and V142I showing the best catalytic activity and substrate specificity were identified. Their double and triple combinatorial mutants synergistically overcame limitations of single mutants, fabricating an excellent M128R/A138V/V142I triple mutant which displayed a 1.21-fold increase in keratin catalytic activity, 1.10-fold enhancement in keratin/casein activity ratio, and a 3.13 °C increase in half-inactivation temperature compared to 4-3Ker. Molecular dynamics simulations revealed enhanced flexibility of critical amino acid residues at the substrate access tunnel, improved global protein rigidity, and heightened hydrophobicity within the active site likely underpinned the increased catalytic activity and substrate specificity. Additionally, the triple mutant improved the feather degradation rate by 32.86 % over the wild-type, far exceeding commercial keratinase in substrate specificity and thermal stability. This study exemplified engineering a typical keratinase with enhanced substrate specificity, catalytic activity, and thermal stability from thermally-stable 4-3Ker, providing a more robust tool for feather degradation.

Synthesis of easily-modified and useful dibenzo-[b,d]azepines by palladium(II)-catalyzed cyclization/addition with a green solvent.

A novel strategy in which palladium(II)-catalyzed tandem cyclization is used to obtain N-heterocyclic architectures containing a seven-membered ring has been developed and used to synthesize a series of derivatives. The reaction uses an eco-friendly mixed solvent (water : EtOH = 2 : 1) instead of DMSO and maintains a high yield (91%). Its potential application value and reaction mechanism have also been explored.

DNA Methylation Analysis Reveals Potential Mechanism in Takifugu rubripes Against Cryptocaryon irritans Infection.

Takifugu rubripes (T. rubripes) is a valuable commercial fish, and Cryptocaryon irritans (C. irritans) has a significant impact on its aquaculture productivity. DNA methylation is one of the earliest discovered ways of gene epigenetic modification and also an important form of modification, as well as an essential type of alteration that regulates gene expression, including immune response. To further explore the anti-infection mechanism of T. rubripes in inhibiting this disease, we determined genome-wide DNA methylation profiles in the gill of T. rubripes using whole-genome bisulfite sequencing (WGBS) and combined with RNA sequence (RNA-seq). A total of 4659 differentially methylated genes (DMGs) in the gene body and 1546 DMGs in the promoter between the infection and control group were identified. And we identified 2501 differentially expressed genes (DEGs), including 1100 upregulated and 1401 downregulated genes. After enrichment analysis, we identified DMGs and DEGs of immune-related pathways including MAPK, Wnt, ErbB, and VEGF signaling pathways, as well as node genes prkcb, myca, tp53, and map2k2a. Based on the RNA-Seq results, we plotted a network graph to demonstrate the relationship between immune pathways and functional related genes, in addition to gene methylation and expression levels. At the same time, we predicted the CpG island and transcription factor of four immune-related key genes prkcb and mapped the gene structure. These unique discoveries could be helpful in the understanding of C. irritans pathogenesis, and the candidate genes screened may serve as optimum methylation-based biomarkers that can be utilized for the correct diagnosis and therapy T. rubripes in the development of the ability to resist C. irritans infection.

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids.

Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 µM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-ß-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.

Uptake patterns for nitrogen and sulfur source by aquatic plants and various nitrogen acquisition strategies: Affected by mining activities.

Understanding the nitrogen and sulfur uptake strategies of mine plants, including sources and preferences for nitrogen forms (ammonium nitrogen (NH4+) vs nitrate nitrogen (NO3-)), is critical to improving understanding of the role of plants in participating in the biogeochemical cycles of nitrogen and sulfur in mining areas. In this study, the stable N and S isotopic compositions of two species of aquatic plants (calamus and reed) in Linhuan mining area were analyzed to determine their absorption strategies for different nitrogen and sulfur sources. The results showed that river water was the largest source of nitrogen and sulfur, contributing 54.6% and 53.9% respectively. NO3- is the main form of nitrogen uptake by reed and calamus, followed by NH4+. In order to adapt to the change of nitrogen form in the environment, reed and calamus tend to absorb and utilize NO3- to maintain their absorption of nitrogen. Mine effluents from mining activities provide at least 12.9% and 16.8% sulfate to reed and calamus respectively, and the effect of mine effluents on reed and calamus sulfur has been underestimated. This study reveals the key factors controlling plant isotope composition, and the use of nitrogen and sulfur isotope composition of aquatic plants can help quantify the level of influence of mining activities, and understand the biogeochemical cycle of nitrogen and sulfur in mining areas.

Synthesis and Characterization of a New Carbon-11 Labeled Positron Emission Tomography Radiotracer for Orexin 2 Receptors Neuroimaging.

Purpose: Orexin receptors (OXRs) play a crucial role in modulating various physiological and neuropsychiatric functions within the central nervous system (CNS). Despite their significance, the precise role of OXRs in the brain remains elusive. Positron emission tomography (PET) imaging is instrumental in unraveling CNS functions, and the development of specific PET tracers for OXRs is a current research focus. Methods: The study investigated MDK-5220, an OX2R-selective agonist with promising binding properties (EC50 on OX2R: 0.023 µM, Ki on hOX2R: 0.14 µM). Synthesized and characterized as an OX2R PET probe, [11C]MDK-5220 was evaluated for its potential as a tracer. Biodistribution studies in mice were conducted to assess OX2R binding selectivity, with particular attention to its interaction with P-glycoprotein (P-gp) on the blood-brain barrier. Results: [11C]MDK-5220 exhibited promising attributes as an OX2R PET probe, demonstrating robust OX2R binding selectivity in biodistribution studies. However, an observed interaction with P-gp impacted its brain uptake. Despite this limitation, [11C]MDK-5220 presents itself as a potential candidate for further development. Discussion: The study provides insights into the functionality of the OX system and the potential of [11C]MDK-5220 as an OX2R PET probe. The observed interaction with P-gp highlights a consideration for future modifications to enhance brain uptake. The findings pave the way for innovative tracer development and propel ongoing research on OX systems, contributing to a deeper understanding of their role in the CNS. Conclusion: [11C]MDK-5220 emerges as a promising OX2R PET probe, despite challenges related to P-gp interaction. This study lays the foundation for further exploration and development of PET probes targeting OXRs, opening avenues for advancing our understanding of OX system functionality within the brain.

Repeated Ketamine Anesthesia during the Neonatal Period Impairs Hippocampal Neurogenesis and Long-Term Neurocognitive Function by Inhibiting Mfn2-Mediated Mitochondrial Fusion in Neural Stem Cells.

The mechanism of ketamine-induced neurotoxicity development remains elusive. Mitochondrial fusion/fission dynamics play a critical role in regulating neurogenesis. Therefore, this study was aimed to evaluate whether mitochondrial dynamics were involved in ketamine-induced impairment of neurogenesis in neonatal rats and long-term synaptic plasticity dysfunction. In the in vivo study, postnatal day 7 (PND-7) rats received intraperitoneal (i.p.) injection of 40 mg/kg ketamine for four consecutive times at 1 h intervals. The present findings revealed that ketamine induced mitochondrial fusion dysfunction in hippocampal neural stem cells (NSCs) by downregulating Mitofusin 2 (Mfn2) expression. In the in vitro study, ketamine treatment at 100 µM for 6 h significantly decreased the Mfn2 expression, and increased ROS generation, decreased mitochondrial membrane potential and ATP levels in cultured hippocampal NSCs. For the interventional study, lentivirus (LV) overexpressing Mfn2 (LV-Mfn2) or control LV vehicle was microinjected into the hippocampal dentate gyrus (DG) 4 days before ketamine administration. Targeted Mfn2 overexpression in the DG region could restore mitochondrial fusion in NSCs and reverse the inhibitory effect of ketamine on NSC proliferation and its faciliatory effect on neuronal differentiation. In addition, synaptic plasticity was evaluated by transmission electron microscopy, Golgi-Cox staining and long-term potentiation (LTP) recordings at 24 h after the end of the behavioral test. Preconditioning with LV-Mfn2 improved long-term cognitive dysfunction after repeated neonatal ketamine exposure by reversing the inhibitory effect of ketamine on synaptic plasticity in the hippocampal DG. The present findings demonstrated that Mfn2-mediated mitochondrial fusion dysfunction plays a critical role in the impairment of long-term neurocognitive function and synaptic plasticity caused by repeated neonatal ketamine exposure by interfering with hippocampal neurogenesis. Thus, Mfn2 might be a novel therapeutic target for the prevention of the developmental neurotoxicity of ketamine.

Quantum squeezing-induced quantum entanglement and EPR steering in a coupled optomechanical system.

We propose a theoretical project in which quantum squeezing induces quantum entanglement and Einstein-Podolsky-Rosen steering in a coupled whispering-gallery-mode optomechanical system. Through pumping the χ(2)-nonlinear resonator with the phase matching condition, the generated squeezed resonator mode and the mechanical mode of the optomechanical resonator can generate strong quantum entanglement and EPR steering, where the squeezing of the nonlinear resonator plays the vital role. The transitions from zero entanglement to strong entanglement and one-way steering to two-way steering can be realized by adjusting the system parameters appropriately. The photon-photon entanglement and steering between the two resonators can also be obtained by deducing the amplitude of the driving laser. Our project does not need an extraordinarily squeezed field, and it is convenient to manipulate and provides a novel and flexible avenue for diverse applications in quantum technology dependent on both optomechanical and photon-photon entanglement and steering.

Advances in macrophage and T cell metabolic reprogramming and immunotherapy in the tumor microenvironment.

Macrophages and T cells in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. However, TME is also characterized by metabolic reprogramming, which may affect macrophage and metabolic activity of T cells and promote tumor escape. Immunotherapy is an approach to fight tumors by stimulating the immune system in the host, but requires support and modulation of cellular metabolism. In this process, the metabolic roles of macrophages and T cells become increasingly important, and their metabolic status and interactions play a critical role in the success of immunotherapy. Therefore, understanding the metabolic state of T cells and macrophages in the TME and the impact of metabolic reprogramming on tumor therapy will help optimize subsequent immunotherapy strategies.