Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines.

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.

Txt2Img-MHN: Remote Sensing Image Generation From Text Using Modern Hopfield Networks.

The synthesis of high-resolution remote sensing images based on text descriptions has great potential in many practical application scenarios. Although deep neural networks have achieved great success in many important remote sensing tasks, generating realistic remote sensing images from text descriptions is still very difficult. To address this challenge, we propose a novel text-to-image modern Hopfield network (Txt2Img-MHN). The main idea of Txt2Img-MHN is to conduct hierarchical prototype learning on both text and image embeddings with modern Hopfield layers. Instead of directly learning concrete but highly diverse text-image joint feature representations for different semantics, Txt2Img-MHN aims to learn the most representative prototypes from text-image embeddings, achieving a coarse-to-fine learning strategy. These learned prototypes can then be utilized to represent more complex semantics in the text-to-image generation task. To better evaluate the realism and semantic consistency of the generated images, we further conduct zero-shot classification on real remote sensing data using the classification model trained on synthesized images. Despite its simplicity, we find that the overall accuracy in the zero-shot classification may serve as a good metric to evaluate the ability to generate an image from text. Extensive experiments on the benchmark remote sensing text-image dataset demonstrate that the proposed Txt2Img-MHN can generate more realistic remote sensing images than existing methods. Code and pre-trained models are available online (https://github.com/YonghaoXu/Txt2Img-MHN).

Ultrashort All-Hydrocarbon Stapled α-Helix Amphiphile as a Potent and Stable Antimicrobial Compound.

The ravaging effect of drug-resistant bacteria has heightened the need for the development of membrane-soluble antimicrobial peptides (AMPs). However, their potential for clinical use is hindered by issues such as poor biocompatibility, salt sensitivity, and proteolytic lability. In this study, a series of ultrashort stapled cyclization heptapeptides were obtained by inserting all-hydrocarbon staples. StRRL with the highest therapeutic index (TI = 36.3) was selected after evaluating its antibacterial and toxic activity. Furthermore, stRRL demonstrated exceptional performance in high-protease and high-salt environments, making it an effective weapon against bacteria like Escherichia coli in a mouse peritonitis-sepsis model. The membrane lytic mechanism of stRRL, which operates from outside to inside, gives it a low drug-resistant tendency. This suggests that stRRL has the potential to replace antibiotics as a powerful candidate in tackling bacterial infection. In conclusion, the ultrashort all-hydrocarbon stapled antimicrobial amphiphiles inaugurated a novel entrance to the advancements of highly stable peptide compounds.

Self-Assembly of Antimicrobial Peptide-Based Micelles Breaks the Limitation of Trypsin.

Targeting the limitation of antimicrobial peptides (AMPs) application in vivo, self-assembled AMPs library with specific nanostructures is expected to gradually overtake monomer AMPs libraries in the future. Peptide polymers are fascinating self-assembling nanoscale structures that have great advantage in biomedical applications because of their satisfactory biocompatibility and versatile properties. Herein, we describe a strategy for inducing the self-assembly of T9W into nanostructured antimicrobial micelles with evidently improved pharmacological properties, that is, PEGylation at the C-terminal of T9W (CT9W1000), an antibacterial biomaterial that self-assembles in aqueous media without exogenous excipients, has been developed. Compared with parental molecular, the CT9W1000 is more effective against Pseudomonas aeruginosa, and its antibacterial spectrum had also been broadened. Additionally, CT9W1000 micelles had higher stability under salt ion, serum, and acid-base environments. Importantly, the self-assembled structure is highly resistant to trypsin degradation, probably allowing T9W to be applied in clinical settings in the future. Mechanistically, by acting on membranes and through supplementary bactericidal mechanisms, CT9W1000 micelles contribute to the antibacterial process. Collectively, CT9W1000 micelles exhibited good biocompatibility in vitro and in vivo, resulting in highly effective treatment in a mouse acute lung injury model induced by P. aeruginosa PAO1 without drug resistance. These advances may profoundly accelerate the clinical transformation of T9W and promote the development of a combination of peptide-based antibiotics and PEGylated nanotechnology.

Effect of Sintering Temperatures on Grain Coarsening Behaviors and Mechanical Properties of W-NiTi Heavy Tungsten Alloys.

W-NiTi tungsten heavy alloys were prepared by an infiltration process using submicron W powders, and the effect of sintering temperatures on grain-coarsening behaviors and the mechanical properties of W-NiTi tungsten heavy alloys were investigated. The microstructures and mechanical properties were investigated using scanning electron microscopy, X-ray diffraction and compression tests. The results showed that tungsten particles were uniformly distributed in the NiTi binder. The W-NiTi tungsten heavy alloys consisted of B19'-NiTi and body-centered cubic W phases. The average tungsten particle sizes of W-NiTi tungsten heavy alloys sintered at 1400 °C, 1480 °C and 1560 °C were 2.62 µm, 4.04 µm and 5.20 µm, respectively. The average tungsten particle size increased with sintering temperatures, while the densities decreased at higher temperatures. The cavities retained in the W-NiTi tungsten heavy alloy sintered at 1560 °C, which degraded the mechanical properties. The calculated grain growth activation energy of W particles in the NiTi binder was 330 kJ/mol, which was higher than those in conventional W-NiFe and W-NiCo tungsten heavy alloys. The higher activation energy means more difficult diffusion process of W atoms in NiTi binders during sintering. Therefore, finer-grained heavy tungsten alloys were more easily obtained by using NiTi binders. Yield strength of W-NiTi tungsten heavy alloys decreased with increasing sintering temperatures due to coarsened tungsten particles.

High-Hole-Mobility Metal-Organic Framework as Dopant-Free Hole Transport Layer for Perovskite Solar Cells.

A dopant-free hole transport layer with high mobility and a low-temperature process is desired for optoelectronic devices. Here, we study a metal-organic framework material with high hole mobility and strong hole extraction capability as an ideal hole transport layer for perovskite solar cells. By utilizing lifting-up method, the thickness controllable floating film of Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 at the gas-liquid interface is transferred onto ITO-coated glass substrate. The Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 film demonstrates high compactness and uniformity. The root-mean-square roughness of the film is 5.5 nm. The ultraviolet photoelectron spectroscopy and the steady-state photoluminescence spectra exhibit the Ni3(HITP)2 film can effectively transfer holes from perovskite film to anode. The perovskite solar cells based on Ni3(HITP)2 as a dopant-free hole transport layer achieve a champion power conversion efficiency of 10.3%. This work broadens the application of metal-organic frameworks in the field of perovskite solar cells.

[Application of supramolecular peptide self-assembly in biomedicine].

In recent years, peptide self-assembly has received much attention because of its ability to form regular and ordered structures with diverse functions. Self-assembled peptides can form aggregates with defined structures under specific conditions. They show different characteristics and advantages (e.g., good biocompatibility and high stability) compared with monomeric peptides, which form the basis for potential application in the fields of drug delivery, tissue engineering, and antiseptics. In this paper, the molecular mechanisms, types and influencing factors of forming self-assembled peptides were reviewed, followed by introducing the latest advances on fibrous peptide hydrogels and self-assembled antimicrobial peptides. Furthermore, the challenges and perspectives for peptide self-assembly technology were discussed.

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability.

The increasing prevalence of antibacterial resistance globally underscores the urgent need for updated antimicrobial peptides (AMPs). Here, we describe a strategy for inducing the self-assembly of protegrin-1 (PG-1) into nanostructured antimicrobial agents with significantly improved pharmacological properties. Our strategy involves PEGylation in the terminals of PG-1 and subsequent self-assembly in aqueous media in the absence of exogenous excipients. Compared with the parent PG-1, the therapeutic index (TI) of NPG750(TIGram-negative bacteria = 17.07) and CPG2000(TIAll = 26.02) was increased. Importantly, NPG750 and CPG2000 offered higher stability toward trypsin degradation. Mechanistically, NPG750 and CPG2000 exerted their bactericidal activity by membrane-active mechanisms due to which microbes were not prone to develop resistance. Our findings proved PEGylation as a simple yet versatile strategy for generating AMP-derived bioactive drugs with excellent antitrypsin hydrolytic ability and lower cytotoxicity. This provides a theoretical basis for the further clinical application of AMPs.

De novo design of a pH-triggered self-assembled ß-hairpin nanopeptide with the dual biological functions for antibacterial and entrapment.

BACKGROUND: Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. RESULTS: A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation-π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 µg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 µg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 µg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety. CONCLUSIONS: Our study revealed the antibacterial activity of a short ß-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections.

Systematically Studying the Optimal Amino Acid Distribution Patterns of the Amphiphilic Structure by Using the Ultrashort Amphiphiles.

Amphipathicity has traditionally been considered to be essential for the de novo design or systematic optimization of antimicrobial peptides (AMPs). However, the current research methods to study the relationship between amphiphilicity and antimicrobial activity are inappropriate, because the key parameters (hydrophobicity, positive charge, etc.) and secondary structure of AMPs are changed. To systematically and accurately study the effects of amphiphilicity on antimicrobial properties of AMPs, we designed parallel series of AMPs with a different order of amino acids in a sequence composed only of Arg and either Trp (WR series) or Leu (LR series), under conditions in which other vital parameters were fixed. Furthermore, based on the WR and LR peptides that can form stable amphiphilic ß-sheet structures in the anionic membrane-mimetic environment, we found that high ß-sheet amphipathic was accompanied by strong antimicrobial activity. Of such peptides, W5 ([RW]4W) and L5 ([RL]4L) with a nicely amphipathic ß-sheet structure possessed the optimal therapeutic index. W5 and L5 also exhibited high stability in vitro and a potent membrane-disruptive mechanism. These results suggest that the alternate arrangement of hydrophobic and hydrophilic residues to form a stable amphipathic ß-sheet structure is an essential factor that significantly affects the antimicrobial properties.

Therapeutic Potential of Trp-Rich Engineered Amphiphiles by Single Hydrophobic Amino Acid End-Tagging.

End-tagging with a single hydrophobic residue contributes to improve the cell selectivity of antimicrobial peptides (AMPs), but systematic studies have been lacking. Thus, this study aimed to systematically investigate how end-tagging with hydrophobic residues at the C-terminus and Gly capped at the N-terminus of W4 (RWRWWWRWR) affects the bioactivity of W4 variants. Among all the hydrophobic residues, only Ala end-tagging improved the antibacterial activity of W4. Meanwhile, Gly capped at the N-terminus could promote the helical propensity of the end-tagged peptides in dodecylphosphocholine micelles, increasing their antimicrobial activities. Of these peptides, GW4A (GRWRWWWRWRA) showed the best antibacterial activity against the 19 species of bacteria tested (GMMIC = 1.86 µM) with low toxicity, thus possessing the highest cell selectivity (TIall = 137.63). It also had rapid sterilization, good salt and serum resistance, and LPS-neutralizing activity. Antibacterial mechanism studies showed that the short peptide GW4A killed bacteria by destroying cell membrane integrity and causing cytoplasmic leakage. Overall, these findings suggested that systematic studies on terminal modifications promoted the development of peptide design theory and provided a potential method for optimization of effective AMPs.

Highly Selective and Reversible Sulfur Dioxide Adsorption on a Microporous Metal-Organic Framework via Polar Sites.

It is very challenging to achieve efficient and deep desulfurization, especially in flue gases with an extremely low SO2 concentration. Herein, we report a microporous metal-organic framework (ELM-12) with specific polar sites and proper pore size for the highly efficient SO2 removal from flue gas and other SO2-containing gases. A high SO2 capacity of 61.2 cm3·g-1 combined with exceptionally outstanding selectivity of SO2/CO2 (30), SO2/CH4 (871), and SO2/N2 (4064) under ambient conditions (i.e., 10:90 mixture at 298 K and 1 bar) was achieved. Notably, the SO2/N2 selectivity is unprecedented among ever reported values of porous materials. Moreover, the dispersion-corrected density functional theory calculations illustrated the superior SO2 capture ability and selectivity arise from the high-density SO2 binding sites of the CF3SO3- group in the pore cavity (Sδ+···Oδ- interactions) and aromatic linkers in the pore walls (Hδ+···Oδ- interactions). Dynamic breakthrough experiments confirm the regeneration stability and excellent separation performance. Furthermore, ELM-12 is also stable after exposure to SO2, water vapor, and organic solvents.