Creation of memory-memory entanglement in a metropolitan quantum network.

Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.

Characterization of an Acinetobacter baumannii Monofunctional Phosphomethylpyrimidine Kinase That Is Inhibited by Pyridoxal Phosphate.

Thiamin and its phosphate derivatives are ubiquitous molecules involved as essential cofactors in many cellular processes. The de novo biosynthesis of thiamin employs the parallel synthesis of 4-methyl-5-(2-hydroxyethyl)thiazole (THZ-P) and 4-amino-2-methyl-5(diphosphooxymethyl) pyrimidine (HMP) pyrophosphate (HMP-PP), which are coupled to generate thiamin phosphate. Most organisms that can biosynthesize thiamin employ a kinase (HMPK or ThiD) to generate HMP-PP. In nearly all cases, this enzyme is bifunctional and can also salvage free HMP, producing HMP-P, the monophosphate precursor of HMP-PP. Here we present high-resolution crystal structures of an HMPK from Acinetobacter baumannii (AbHMPK), both unliganded and with pyridoxal 5-phosphate (PLP) noncovalently bound. Despite the similarity between HMPK and pyridoxal kinase enzymes, our kinetics analysis indicates that AbHMPK accepts HMP exclusively as a substrate and cannot turn over pyridoxal, pyridoxamine, or pyridoxine nor does it display phosphatase activity. PLP does, however, act as a weak inhibitor of AbHMPK with an IC50 of 768 µM. Surprisingly, unlike other HMPKs, AbHMPK catalyzes only the phosphorylation of HMP and does not generate the diphosphate HMP-PP. This suggests that an additional kinase is present in A. baumannii, or an alternative mechanism is in operation to complete the biosynthesis of thiamin.

PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway.

OBJECTIVE: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms. METHODS: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry. RESULTS: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells. CONCLUSION: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.

Causality of the gut microbiome and atherosclerosis-related lipids: a bidirectional Mendelian Randomization study.

AIMS: Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids. METHODS: We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates. RESULTS: The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362-0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis. CONCLUSION: The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.

Microcystin-RR promote lipid accumulation through CD36 mediated signal pathway and fatty acid uptake in HepG2 cells.

Microcystins (MC)-RR is a significant analogue of MC-LR, which has been identified as a hepatotoxin capable of influencing lipid metabolism and promoting the progression of liver-related metabolic diseases. However, the toxicity and biological function of MC-RR are still not well understood. In this study, the toxic effects and its role in lipid metabolism of MC-RR were investigated in hepatoblastoma cells (HepG2cells). The results demonstrated that MC-RR dose-dependently reduced cell viability and induced apoptosis. Additionally, even at low concentrations, MC-RR promoted lipid accumulation through up-regulating levels of triglyceride, total cholesterol, phosphatidylcholines and phosphatidylethaolamine in HepG2 cells, with no impact on cell viability. Proteomics and transcriptomics analysis further revealed significant alterations in the protein and gene expression profiles in HepG2 cells treated with MC-RR. Bioinformatic analysis, along with subsequent validation, indicated the upregulation of CD36 and activation of the AMPK and PI3K/AKT/mTOR in response to MC-RR exposure. Finally, knockdown of CD36 markedly ameliorated MC-RR-induced lipid accumulation in HepG2 cells. These findings collectively suggest that MC-RR promotes lipid accumulation in HepG2 cells through CD36-mediated signal pathway and fatty acid uptake. Our findings provide new insights into the hepatotoxic mechanism of MC-RR.

Expression and characterization of the new antimicrobial peptide AP138L-arg26 anti Staphylococcus aureus.

The low activity and yield of antimicrobial peptides (AMPs) are pressing problems. The improvement of activity and yield through modification and heterologous expression, a potential way to solve the problem, is a research hot-pot. In this work, a new plectasin-derived variant L-type AP138 (AP138L-arg26) was constructed for the study of recombination expression and druggablity. As a result, the total protein concentration of AP138L-arg26 was 3.1 mg/mL in Pichia pastoris X-33 supernatant after 5 days of induction expression in a 5-L fermenter. The recombinant peptide AP138L-arg26 has potential antibacterial activity against selected standard and clinical Gram-positive bacteria (G+, minimum inhibitory concentration (MIC) 2-16 µg/mL) and high stability under different conditions (temperature, pH, ion concentration) and 2 × MIC of AP138L-arg26 could rapidly kill Staphylococcus aureus (S. aureus) (> 99.99%) within 1.5 h. It showed a high safety in vivo and in vivo and a long post-antibiotic effect (PAE, 1.91 h) compared with vancomycin (1.2 h). Furthermore, the bactericidal mechanism was revealed from two dimensions related to its disruption of the cell membrane resulting in intracellular potassium leakage (2.5-fold higher than control), and an increase in intracellular adenosine triphosphate (ATP), and reactive oxygen species (ROS), the decrease of lactate dehydrogenase (LDH) and further intervening metabolism in S. aureus. These results indicate that AP138L-arg26 as a new peptide candidate could be used for more in-depth development in the future. KEY POINTS: • The AP138L-arg26 was expressed in the P. pastoris expression system with high yield • The AP138 L-arg26 showed high stability and safety in vitro and in vivo • The AP138L-arg26 killed S. aureus by affecting cell membranes and metabolism.

Pharmacokinetics and pharmacodynamics of antibacterial peptide NZX in Staphylococcus aureus mastitis mouse model.

Staphylococcus aureus is associated with dairy mastitis, which causes serious economic losses to dairy farming industry. Antibacterial peptide NZX showed good antibacterial activity against S. aureus. This study aimed to evaluate pharmacokinetics and pharmacodynamics of NZX against S. aureus-induced mouse mastitis. NZX exhibited potent in vitro antibacterial activity against the test S. aureus strains (minimal inhibitory concentration (MIC): 0.23-0.46 µM), low mutant prevention concentration (MPC: 1.18-3.68 µM), and a long post antibiotic effect (PAE: 2.20-8.84 h), which was superior to those of lincomycin and ceftiofur. Antibacterial mechanisms showed that NZX could penetrate the cell membrane, resulting in obvious cell membrane perforation and morphological changes, and bind to intracellular DNA. Furthermore, NZX had a good stability in milk environment (retention rate: 85.36%, 24 h) than that in mammary homogenate (47.90%, 24 h). In mouse mastitis model, NZX (25-400 µg/gland) could significantly reduce the bacterial load of mammary tissue in a dose-dependent manner. In addition, NZX (100 µg/gland) could relieve the inflammatory symptoms of mammary tissue, and significantly decreased its pathological scores. The concentration-time curve of NZX (100 µg/gland) in the mammary tissue was plotted and the corresponding pharmacokinetic parameters were obtained by non-compartment model calculation. Those parameters of Tmax, T1/2, Cmax and AUC were 0.5 h, 35.11 h, 32.49 µg/g and 391 µg·h/g, respectively. Therefore, these results suggest that NZX could act as a promising candidate for treating dairy mastitis disease caused by S. aureus. KEY POINTS: • NZX could kill S. aureus by dual mechanism involved in membrane and DNA disruption • NZX could relieve S. aureus-induced mouse mastitis • Pharmacokinetic parameters of NZX in mouse mammary gland were obtained.

Fault logic and data-driven model for operation reliability analysis of the flap deflection angle.

To effectively perform the reliability analysis of the flap deflection angle, the reliability analysis framework is developed by introducing fault logic and a data-driven model. Herein, the fault logic analysis is used to study the fault mechanism and filter out the characteristic fault parameters that can be used to collect input data for data-driven modelling; the data-driven modelling is employed to establish a reliability analysis model with a small amount of input data. Under this proposed framework, the improved dung beetle optimization algorithm for back propagation (IDBO-BP) method is developed to perform the reliability modelling of the flap deflection angle. To validate the effectiveness of the proposed framework, we study the fault logic of flap symmetry and establish a surrogate model of flap deflection based on the fault parameters and the IDBO-BP algorithm. According to the predicted results of the flap deflection angle, the reliability model based on the fault mechanism can reflect the actual flap motion. At the same time, the proposed IDBO-BP algorithm has excellent modelling and simulation property by comparing with other optimization algorithms. Thus, the efforts of this study provide a new solution to the problem of reliable analysis with uncertain fault parameters. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Effects of dietary supplementation of bovine lactoferrin on growth performance, immune function and intestinal health in weaning piglets.

Weaning is a crucial period in the pig's life cycle, which is frequently followed by gastrointestinal (GI) infections, diarrhea and even death. This study focused on the impact of bovine lactoferrin (bLF) supplementation on the intestinal health of weaning piglets. Weaning piglets (Duroc × Landrace × Yorkshire, 23 days) were randomly allocated into four groups, which included negative control group (CON): basic diet; positive control group (ANT): basic diet + 20 mg/kg flavomycin + 100 mg/kg aureomycin; treatment group bLF-A: basic diet + 1 g/kg bLF; treatment group bLF-B: basic diet + 3 g/kg bLF. The result showed that dietary supplementation of bLF can improve growth performance and reduce diarrhea, which exhibits dose-dependency (P < 0.05). Compared with CON group, supplementation with bLF significantly improved immunity, and increased villus height and ratio of villus height/crypt depth at the small intestinal mucosa (P < 0.05). The mRNA expression of claudin-1, occludin and ZO-1 was greatly increased in the ileum of bLF group on days 7 and 14 (P < 0.05). Furthermore, the supplementation of bLF increased the abundance of Lactobacillus and Bifidobacterium and decreased the abundance of Escherichia coli in the cecum on day 7 (P < 0.05). The dietary supplementation of bLF enhanced the growth performance, reduced diarrhea rate in weaning piglets by improving intestinal immunity, morphology and barrier function, balancing intestinal microbiota. And bLF can be a promising feed additive in relieving stress situation of weaning piglets.

High-Yield Preparation of American Oyster Defensin (AOD) via a Small and Acidic Fusion Tag and Its Functional Characterization.

The marine peptide, American oyster defensin (AOD), is derived from Crassostrea virginica and exhibits a potent bactericidal effect. However, recombinant preparation has not been achieved due to the high charge and hydrophobicity. Although the traditional fusion tags such as Trx and SUMO shield the effects of target peptides on the host, their large molecular weight (12-20 kDa) leads to the yields lower than 20% of the fusion protein. In this study, a short and acidic fusion tag was employed with a compact structure of only 1 kDa. Following 72 h of induction in a 5 L fermenter, the supernatant exhibited a total protein concentration of 587 mg/L. The recombinant AOD was subsequently purified through affinity chromatography and enterokinase cleavage, resulting in the final yield of 216 mg/L and a purity exceeding 93%. The minimum inhibitory concentrations (MICs) of AOD against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus galactis ranged from 4 to 8 µg/mL. Moreover, time-killing curves indicated that AOD achieved a bactericidal rate of 99.9% against the clinical strain S. epidermidis G-81 within 0.5 h at concentrations of 2× and 4× MIC. Additionally, the activity of AOD was unchanged after treatment with artificial gastric fluid and intestinal fluid for 4 h. Biocompatibility testing demonstrated that AOD, at a concentration of 128 µg/mL, exhibited a hemolysis rate of less than 0.5% and a cell survival rate of over 83%. Furthermore, AOD's in vivo therapeutic efficacy against mouse subcutaneous abscess revealed its capability to restrain bacterial proliferation and reduce bacterial load, surpassing that of antibiotic lincomycin. These findings indicate AOD's potential for clinical usage.

Perspective: A proposal on solutions of modern supply chain construction for lactoferrin.

Lactoferrin is an iron-binding glycoprotein of the transferrin family that is found in most bodily fluids of mammals and has a variety of biological and beneficial functions, with great importance in health enhancement as a supplement for humans and other animals. More than 300 t of lactoferrin were produced in 2021, and this number is expected to grow yearly by 10% to 12%, to over 580 t in 2030. With new and important functions of lactoferrin being revealed and studied, focus on its industrial production and application is increasing accordingly. However, lactoferrin is mainly sourced from cheese whey or skim milk by cation-exchange column chromatography, which is a costly and low-quality method. A potential solution for lactoferrin global supply chain construction is proposed in this article as a complement to traditional routes of purification from whey or skim milk. The large-scale production of lactoferrin, mainly by recombinant yeast, mammal, and grain systems, as well as the market niche and product design, are discussed.

A multiscale residual U-net architecture for super-resolution ultrasonic phased array imaging from full matrix capture data.

Ultrasonic phased array imaging using full-matrix capture (FMC) has raised great interest among various communities, including the nondestructive testing community, as it makes full use of the echo space to provide preferable visualization performance of inhomogeneities. The conventional way of FMC data postprocessing for imaging is through beamforming approaches, such as delay-and-sum, which suffers from limited imaging resolution and contrast-to-noise ratio. To tackle these difficulties, we propose a deep learning (DL)-based image forming approach, termed FMC-Net, to reconstruct high-quality ultrasonic images directly from FMC data. Benefitting from the remarkable capability of DL to approximate nonlinear mapping, the developed FMC-Net automatically models the underlying nonlinear wave-matter interactions; thus, it is trained end-to-end to link the FMC data to the spatial distribution of the acoustic scattering coefficient of the inspected object. Specifically, the FMC-Net is an encoder-decoder architecture composed of multiscale residual modules that make local perception at different scales for the transmitter-receiver pair combinations in the FMC data. We numerically and experimentally compared the DL imaging results to the total focusing method and wavenumber algorithm and demonstrated that the proposed FMC-Net remarkably outperforms conventional methods in terms of exceeding resolution limit and visualizing subwavelength defects. It is expected that the proposed DL approach can benefit a variety of ultrasonic array imaging applications.

Thinking on the Construction of Antimicrobial Peptide Databases: Powerful Tools for the Molecular Design and Screening.

With the accelerating growth of antimicrobial resistance (AMR), there is an urgent need for new antimicrobial agents with low or no AMR. Antimicrobial peptides (AMPs) have been extensively studied as alternatives to antibiotics (ATAs). Coupled with the new generation of high-throughput technology for AMP mining, the number of derivatives has increased dramatically, but manual running is time-consuming and laborious. Therefore, it is necessary to establish databases that combine computer algorithms to summarize, analyze, and design new AMPs. A number of AMP databases have already been established, such as the Antimicrobial Peptides Database (APD), the Collection of Antimicrobial Peptides (CAMP), the Database of Antimicrobial Activity and Structure of Peptides (DBAASP), and the Database of Antimicrobial Peptides (dbAMPs). These four AMP databases are comprehensive and are widely used. This review aims to cover the construction, evolution, characteristic function, prediction, and design of these four AMP databases. It also offers ideas for the improvement and application of these databases based on merging the various advantages of these four peptide libraries. This review promotes research and development into new AMPs and lays their foundation in the fields of druggability and clinical precision treatment.

Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.

Overweight and obese (OW/OB) adults are at increased risk of hypertension due to visceral adipose tissue (VAT) inflammation. In this study, we explored gene level differences in the VAT of hypertensive and normotensive OW/OB patients. VAT samples obtained from six OW/OB adults (three hypertensive, three normotensive) were subjected to transcriptome sequencing analysis. Gene set enrichment analysis was conducted for all gene expression data to identify differentially expressed genes (DEGs) with |log2 (fold change)| ≥ 1 and q < 0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed on the DEGs, and hub genes were identified by constructing a protein-protein interaction (PPI) network. The proposed hub genes were validated using quantitative real-time PCR in ten other samples from five hypertensive and five normotensive patients. In addition, we performed ROC analysis and Spearman correlation analysis. A total of 84 DEGs were identified between VAT samples from OW/OB patients with and without hypertension, among which 21 were significantly upregulated and 63 were significantly downregulated. Bioinformatics analysis revealed that spleen function was related to hypertension in OW/OB adults. Meanwhile, PPI network analysis identified the following top 10 hub genes: CD79A, CR2, SELL, CD22, IL7R, CCR7, TNFRSF13C, CXCR4, POU2AF1, and JAK3. Through qPCR verification, we found that CXCR4, CD22, and IL7R were statistically significant. qPCR verification suggested that RELA was statistically significant. However, qPCR verification indicated that NFKB1 and KLF2 were not statistically significant. These hub genes were mainly regulated by the transcription factor RELA. The AUC of ROC analysis for CXCR4, IL7R, and CD22 was 0.92. What is more, VAT CXCR4 and CD22 were positively related to RELA relative expression levels. Taken together, our research demonstrates that CXCR4, IL7R, and CD22 related to VAT in hypertensive OW/OB adults could serve as future therapeutic targets.

C-terminal mini-PEGylation of a marine peptide N6 had potent antibacterial and anti-inflammatory properties against Escherichia coli and Salmonella strains in vitro and in vivo.

BACKGROUND: Enteropathogenic Escherichia coli and Salmonella pullorum are two important groups of zoonotic pathogens. At present, the treatment of intestinal pathogenic bacteria infection mainly relies on antibiotics, which directly inhibit or kill the pathogenic bacteria. However, due to long-term irrational, excessive use or abuse, bacteria have developed different degrees of drug resistance. N6, an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is poorly resistant to enzymatic hydrolysis and distribution in vivo. Polyethylene glycol (PEG) is an extensively studied polymer and commonly used in protein or peptide drugs to improve their therapeutic potential. Here, we modified the N-/C-terminal or Cys residue of N6 with liner PEGn of different lengths (n = 2, 6,12, and 24), and the effects of PEGylation of N6 on the stability, toxicity, bactericidal mechanism, distribution and efficacy were investigated in vitro and in vivo. RESULTS: The antimicrobial activity of the peptide showed that PEGylated N6 at the C-terminus (n = 2, N6-COOH-miniPEG) had potent activity against Gram-negative bacteria; PEGylated N6 at the N-terminus and Cys residues showed low or no activity with increasing lengths of PEG. N6-COOH-miniPEG has higher stability in trypsin than the parent peptide-N6. N6-COOH-miniPEG significantly regulated cytokine expression in lipopolysaccharides (LPS)-induced RAW 264.7 cells, and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were reduced by 31.21%, 65.62% and 44.12%, respectively, lower than those of N6 (-0.06%, -12.36% and -12.73%); N6-COOH-miniPEG increased the level of IL-10 (37.83%), higher than N6 (-10.21%). The data indicated that N6-COOH-miniPEG has more potent anti-inflammatory and immune-regulatory effect than N6 in LPS-stimulated RAW 264.7 cells. N6-COOH-miniPEG exhibited a much wider biodistribution in mice and prolonged in vivo half-time. FITC-labeled N6-COOH-miniPEG was distributed throughout the body of mice in the range of 0.75 - 2 h after injection, while FITC-labeled N6 only concentrated in the abdominal cavity of mice after injection, and the distribution range was narrow. N6-COOH-miniPEG improved the survival rates of mice challenged with E. coli or S. pullorum, downregulated the levels of TNF-α, IL-6, IL-1ß and IL-10 in the serum of LPS-infected mice, and alleviated multiple-organ injuries (the liver, spleen, kidney, and lung), superior to antibiotics, but slightly inferior to N6. CONCLUSIONS: The antibacterial activity, bactericidal mechanism and cytotoxicity of N6-COOH-miniPEG and N6 were similar. N6-COOH-miniPEG has a higher resistance to trysin than N6. The distribution of N6-COOH-miniPEG in mice was superior to that of N6. In exploring the modulatory effects of antimicrobial peptides on cytokines, N6-COOH-miniPEG had stronger anti-inflammatory and immunomodulatory effects than N6. The results suggested that C-terminal PEGylated N6 may provide an opportunity for the development of effective anti-inflammatory and antibacterial peptides.

Di- and Tetranuclear Dysprosium Single-Molecule Magnets Bridged by Unprecedentedly Disassembled Nitrogen-Enriched Tetrazine Derivatives.

A series of di- and tetranuclear lanthanide complexes with the formulas [Dy2bmzch(tmhd)5 (CH3OH)]·CH3OH (1), [Dy2bmzch(dbm)4 (CH3O)(CH3OH)]·0.5CH3OH·0.5H2O (2), and Dy4bmzch(btfa)10 (3), where tmhd = 2,2,6,6-tetramethyl-3,5-heptanedionate, dbm = dibenzoylmethane, btfa = benzoyltrifluoroacetone, and bmzch = (Z)-N-[(E)-pyrimidin-2-ylmethylene]pyrimidine-2-carbohydrazonate, were structurally and magnetically characterized. More strikingly, although the nitrogen-enriched bridged ligand 3,6-di(pyrimidin-2-yl)-1,2,4,5-tetrazine (bmtz) was initially adopted, the structures of the complexes obtained indicated that bmtz underwent unprecedented asymmetric ring opening and generated a new ligand bmzch. Combined with different ß-diketonates, di- and tetranuclear dysprosium complexes were constructed in which the structural patterns are very sensitive to the selected ß-diketonates. In view of this, the bilateral and unilateral dinuclear Dy2 complexes 1 and 2 and tetranuclear Dy4 complex 3 were obtained by choosing different ß-diketonates. Magnetic test results reveal that both complexes 1 and 3 showcase typical slow magnetic relaxation behavior without an external direct-current field and the effective energy barrier of the latter is almost twice that of the former, while complex 2 only displays in-field single-molecule-magnetic behavior. Also of note is that these are the first tetrazine-type dysprosium-based single-molecule-magnets undergoing in situ asymmetric ring-opening reaction of this ligand that are formed.

Antibacterial peptide NZ2114-loaded hydrogel accelerates Staphylococcus aureus-infected wound healing.

Wound infection caused by Staphylococcus aureus (S. aureus) is a great challenge which has caused significant burden and economic loss to the medical system. NZ2114, a plectasin-derived peptide, is an antibacterial agent for preventing and treating S. aureus infection, especially for methicillin-resistant S. aureus (MRSA) infection. Here, three-dimensional reticulated antimicrobial peptide (AMP) NZ2114 hydrogels were developed based on hydroxypropyl cellulose (HPC) and sodium alginate (SA); they displayed sustained and stable release properties (97.88 ± 1.79% and 91.1 ± 10.52% release rate in 72 h, respectively) and good short-term cytocompatibility and hemocompatibility. But the HPC-NZ2114 hydrogel had a smaller pore size (diameter 0.832 ± 0.420 µm vs. 3.912 ± 2.881 µm) and better mechanical properties than that of the SA-NZ2114 hydrogel. HPC/SA-NZ2114 hydrogels possess efficient antimicrobial activity in vitro and in vivo. In a full-thickness skin defect model, the wound closure of the 1.024 mg/g HPC-NZ2114 hydrogel group was superior to those of the SA-NZ2114 hydrogel and antibiotic groups on day 7. The HPC-NZ2114 hydrogel accelerated wound healing by reducing inflammation and promoting the production of vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and angiogenesis (CD31) through histological and immunohistochemistry evaluation. These data indicated that the HPC-NZ2114 hydrogel is an excellent candidate for S. aureus infection wound dressing. KEY POINTS: •NZ2114 hydrogels showed potential in vitro bactericidal activity against S. aureus •NZ2114 hydrogels could release continuously for 72 h and had good biocompatibility •NZ2114 hydrogels could effectively promote S. aureus-infected wound healing.

Resistance response to Arenicin derivatives in Escherichia coli.

The rising prevalence of antibiotic resistance poses the greatest health threats. Antimicrobial peptides (AMPs) are regarded as the potentially effective therapy. To avoid current crisis of antibiotic resistance, a comprehensive understanding of AMP resistance is necessary before clinical application. In this study, the development of resistance to the anti-Gram-negative bacteria peptide N6NH2 (21 residues, ß-sheet) was characterized in E. coli ATCC25922. Three N6NH2-resistant E. coli mutants with 32-fold increase in MIC were isolated by serially passaging bacterial lineages in progressively increasing concentrations of N6NH2 and we mainly focus on the phenotype of N6NH2-resistant bacteria different from sensitive bacteria. The results showed that the resistance mechanism was attributed to synergy effect of multiple mechanisms: (i) increase biofilm formation capacity (3 ~ 4-fold); (ii) weaken the affinity of lipopolysaccharide (LPS) with N6NH2 (3 ~ 8-fold); and (iii) change the cell membrane permeability and potential. Interestingly, a chimeric peptide-G6, also a N6NH2 analog, which keep the same antibacterial activity to both wild-type and resistant clones (MIC value: 16 µg/mL), could curb N6NH2-resistant mutants by stronger inhibition of biofilm formation, stronger affinity with LPS, and stronger membrane permeability and depolarization than that of N6NH2.

A prospective on multiple biological activities of lactoferrin contributing to piglet welfare.

Piglets, especially weaning piglets, show a lower level of immunity and higher morbidity and mortality, owing to their rapid growth, physiological immaturity, and gradual reduction of maternal antibodies, which seriously affects their growth and thus, value. It is important that piglets adapt to nutrient digestion and absorption and develop sound intestinal function and colonization with gut microbiota as soon as possible during their early life stage. Lactoferrin is a natural glycoprotein polypeptide that is part of the transferrin family. It is widely found in mucosal secretions such as saliva and tears, and most highly in milk and colostrum. As a multifunctional bioactive protein and a recommended food additive, lactoferrin is a potential alternative therapy to antibiotics and health promoting additive for piglet nutrition and development. It is expected that lactoferrin, as a natural food additive, could play an important role in maintaining pig health and development. This review examines the following known beneficial effects of lactoferrin: improves the digestion and capacity for absorption in the intestinal tract; promotes the absorption of iron and reduces the incidence of iron deficiency anemia; regulates intestinal function and helps to balance the microbial biota; and enhances the resistance to disease of the piglets via modulating and enhancing the immune system.

Comparative Study of NO and CO Oxidation Reactions on Single-Atom Catalysts Anchored Graphene-like Monolayer.

Noble metal single-atom catalysts (NM-SACs) anchored at novel graphene-like supports has attracted enormous interests. Gas sensitivity, catalytic activity, and d-band centers of single NM (Pt and Pd) atoms at graphenylene (graphenylene-NM) are investigated using first-principle calculations. The adsorption geometries of gas reactants on graphenylene-NM sheets are analyzed. It is found that the adsorption energies of reactant species on graphenylene-Pt are larger than those on graphenylene-Pd, because the d-band center of the Pt atom is closeser to the Fermi level. The NO and CO oxidation reactions on graphenylene-NM are investigated via four catalytic mechanisms, including Langmuir-Hinshelwood (LH), Eley-Rideal (ER), New ER (NER), and termolecular ER (TER). The results show that the NO and CO oxidations via LH and TER mechanisms can occur owing to the relatively small energy barriers. Moreover, the interaction of 2NO+2CO via ER mechanism is the energetically more favorable reaction. Although the NO oxidation via the NER mechanism has rather low energy barriers, the reaction is unlikely to occur due to the low adsorption energy of O2 compared with CO and NO. This research may provide guidance for exploring the catalytic performance of SACs on graphene-like materials to remove toxic gas molecules.