Virucidal effects of eucalyptus essential oil on porcine reproductive and respiratory syndrome virus.

Currently, the efficacy of vaccination for preventing and controlling PRRSV is insufficient. Therefore, there is an urgent need for novel effective preventive strategies. This study aimed to investigate the antiviral effect of Eucalyptus essential oil (EEO) against PRRSV in vitro. Marc-145 cells were infected with PRRSV (rJXA1-R), and the toxicity of EEO in the cells was measured using the Cell Counting Kit-8 method. Additionally, the antiviral effect of EEO on PRRSV-infected cells was assessed using three treatment methods: drug administration post-PRRSV inoculation (post-treatment), drug administration before PRRSV inoculation (pre-treatment), and simultaneous drug administration and PRRSV inoculation (co-treatment). The EEO could not inhibit virus adsorption and/or replication since post-treatment and pre-treatment did not prevent viral infectivity. However, EEO exerted a significant virucidal effect on PRRSV. When PRRSV-infected cells were treated with 0.0156, 0.0312, and 0.0625% EEO, the cell survival rates were 55.37, 118.96, and 121.67%, respectively, and the titer of progeny virions decreased from 5.77 Log10TCID50 to 5.21 Log10TCID50, 0.55 Log10TCID50, and less than 0.167 Log10TCID50, respectively (where TCID50 is the 50% tissue culture infected dose). The fluorescence intensity of the PRRSV N protein significantly decreased in the indirect immunofluorescence assay. When cells were co-treated with EEO (0.0625%) and PRRSV (1000 TCID50) for 15 min, the viral particles were inactivated, and PRRSV (1000 TCID50) particles loss infectivity when the co-treatment time reached 60 min. In a word, EEO has no obvious therapeutic effect on PRRSV infection, but it can effectively inactivate virus particles and make them lose the ability to infect cells. These findings provide insights for the development and use of EEO to treat PRRS.

Functional characterisation and modification of a novel Kunitzin peptide for use as an anti-trypsin antimicrobial peptide against drug-resistant Escherichia coli.

In recent decades, antimicrobial peptides (AMPs) have emerged as highly promising candidates for the next generation of antibiotic agents, garnering significant attention. Although their potent antimicrobial activities and ability to combat drug resistance make them stand out among alternative agents, their poor stability has presented a great challenge for further development. In this work, we report a novel Kunitzin AMP, Kunitzin-OL, from the frog Odorrana lividia, exhibiting dual antimicrobial and anti-trypsin activities. Through functional screening and comparison with previously reported Kunitzin peptides, we serendipitously discovered a unique motif (-KVKF-) and unveiled its crucial role in the antibacterial functions of Kunitzin-OL by modifying it through motif removal and duplication. Among the designed derivatives, peptides 4 and 8 demonstrated remarkable antimicrobial activities and low cytotoxicity, with high therapeutic index (TI) values (TI4 = 20.8, TI8 = 20.8). Furthermore, they showed potent antibacterial efficacy against drug-resistant Escherichia coli strains and exhibited lipopolysaccharide (LPS)-neutralising activity, effectively alleviating LPS-induced inflammatory responses. Overall, our findings provide a new short motif for designing effective AMP drugs and highlight the potential of the Kunitztin trypsin inhibitory loop as a valuable motif for the design of AMPs with enhancing proteolytic stability.

Analysis of pathogen distribution and sTREM-1 and miR-126 levels in patients with pulmonary infection after craniocerebral injury.

BACKGROUND: sTREM-1H and miR-126 play crucial roles in inflammation and immune responses, yet their involvement in patients with pulmonary infection following cranial injury remains understudied. OBJECTIVE: The distribution of pathogens causing infection in patients with pulmonary infection after craniocerebral injury was explored, and the changes in the levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and miR-126 in peripheral blood were analyzed. METHODS: In this study, 60 patients (study group) with postoperative lung infection in craniocerebral injury treated from January 2019 to December 2, 2021, and 60 patients without lung infection were selected as the control group. The study group received anti-infection treatment. The infection pathogen of the study group was tested, and the changes of sTREM-1 and miR-126 levels in the peripheral blood of the study and control groups were recorded to explore the diagnosis and predictive Value of prognostic death. RESULTS: 66 pathogens were detected, including 18 gram-positive bacteria, 42 gram-negative bacteria, and 6 fungi. The sTREM-1 level was higher than the control group, and the miR-126 level was lower than the control group. By ROC curve analysis, the diagnostic AUC values of both patients were 0.907 and 0.848, respectively (P< 0.05). Compared to those in the study group, patients had decreased sTREM-1 levels and increased miR-126 levels after treatment (P< 0.05). Compared with the survival group, patients in the death group had increased sTREM-1 levels and decreased miR-126 levels, and ROC curve analysis, the predicted AUC death values were 0.854 and 0.862, respectively. CONCLUSION: Gram-negative bacteria, with increased peripheral sTREM-1 levels and decreased miR-126 levels. The levels of sTREM-1 and miR-126 have specific diagnostic and prognostic Values for pulmonary infection after craniocerebral injury. However, the study's conclusions are drawn from a limited sample and short-term data, which might limit their broader applicability. Future studies with larger populations and longitudinal designs are required to confirm these findings and determine these biomarkers' robustness across different settings. Further research should also explore how these biomarkers influence patient outcomes in craniocerebral injuries.

Enhancement of Antimicrobial Function by L/D-Lysine Substitution on a Novel Broad-Spectrum Antimicrobial Peptide, Phylloseptin-TO2: A Structure-Related Activity Research Study.

Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from Phyllomedusidae frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH2), identified from the skin secretion of Phyllomedusa tomopterna, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.

Discovery and engineering of a novel peptide, Temporin-WY2, with enhanced in vitro and in vivo efficacy against multi-drug resistant bacteria.

Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future.

Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms.

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, Odorrana andersonii, by using the 'shotgun' cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of P. aeruginosa biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by Pseudomonas aeruginosa.

1H-NMR-based metabolomics reveals the preventive effect of Enteromorpha prolifera polysaccharides on diabetes in Zucker diabetic fatty rats.

The primary objective of this investigation was to explore the beneficial impacts of Enteromorpha prolifera polysaccharide (EP) on dysglycemia in Zucker diabetic fatty (ZDF) rats, while also shedding light on its potential mechanism using 1H-NMR-based metabolomics. The results demonstrated a noteworthy reduction in fasting blood glucose (FBG, 46.3%), fasting insulin (50.17%), glycosylated hemoglobin A1c (HbA1c, 44.1%), and homeostatic model assessment of insulin resistance (HOMA-IR, 59.75%) following EP administration, while the insulin sensitivity index (ISI, 19.6%) and homeostatic model assessment of ß-cell function (HOMA-ß, 2.5-fold) were significantly increased. These findings indicate that EP enhances ß-cell function, increases insulin sensitivity, and improves insulin resistance caused by diabetes. Moreover, EP significantly reduced serum lipid levels, suggesting improvement of dyslipidemia. Through the analysis of serum metabolomics, 17 metabolites were found to be altered in diabetic rats, 14 of which were upregulated and 3 of which were downregulated. Notably, the administration of EP successfully reversed the abnormal levels of 9 out of the 17 metabolites. Pathway analysis further revealed that EP treatment partially restored metabolic dysfunction, with notable effects observed in valine, leucine, and isoleucine metabolism; aminoacyl-transfer RNA (tRNA) biosynthesis; and ketone body metabolism. These findings collectively indicate the potential therapeutic efficacy of EP in preventing glycemic abnormalities and improving insulin resistance. Thus, EP holds promise as a valuable treatment option for individuals with diabetes.

Homologous polydopamine ameliorates haemolysis of melittin for enhancing its anticancer efficacy.

Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL-polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.

An Effective Modification Strategy to Build Multifunctional Peptides Based on a Trypsin Inhibitory Peptide of the Kunitz Family.

Peptides with antimicrobial activity or protease inhibitory activity are potential candidates to supplement traditional antibiotics or cancer chemotherapies. However, the potential of many peptides are limited by drawbacks such as cytotoxicity or susceptibility to hydrolysis. Therefore, strategies to modify the structure of promising peptides may represent an effective approach for developing more promising clinical candidates. In this study, the mature peptide OSTI-1949, a Kunitz-type inhibitor from Odorrana schmackeri, and four designed analogues were successfully synthesised. In contrast to the parent peptide, the analogues showed impressive multi-functionality including antimicrobial, anticancer, and trypsin inhibitory activities. In terms of safety, there were no obvious changes observed in the haemolytic activity at the highest tested concentration, and the analogue OSTI-2461 showed an increase in activity against cancer cell lines without cytotoxicity to normal cells (HaCaT). In summary, through structural modification of a natural Kunitz-type peptide, the biological activity of analogues was improved whilst retaining low cytotoxicity. The strategy of helicity enhancement by forming an artificial α-helix and ß-sheet structure provides a promising way to develop original bioactive peptides for clinical therapeutics.

Fabrication and characterization of curcumin-loaded nanoparticles using licorice protein isolate from Radix Glycyrrhizae.

Licorice was widely used in food and herbal medicine. In its extract industry, a substantial amount of licorice protein was produced and discarded as waste. Herein, we extracted Licorice Protein Isolate (LPI) and explored its potential as a curcumin nanocarrier. Using a pH-driven method, we fabricated LPI-curcumin nanoparticles with diameters ranging from 129.30 ± 3.21 nm to 75.03 ± 1.19 nm, depending on the LPI/curcumin molar ratio. The formation of LPI-curcumin nanoparticles was primarily driven by hydrophobic interactions, with curcumin entrapped in LPI being in an amorphous form. These nanoparticles significantly enhanced curcumin properties in terms of solubility, photochemical stability, and stability under varying pH, storage, and physiological conditions. Moreover, the loaded curcumin exhibited a 2.58-fold increase in cellular antioxidant activity on RAW 264.7 cells and a 1.86-fold increase in antitumor activity against HepG2 cells compared to its free form. These findings suggested that LPI could potentially serve as a promising novel delivery material.

A promising antibiotic candidate, brevinin-1 analogue 5R, against drug-resistant bacteria, with insights into its membrane-targeting mechanism.

In recent decades, antimicrobial peptides (AMPs) have held great promise as novel antibiotic agents. However, they have generally been excluded from clinical use due to certain limitations, such as poor biocompatibility and sensitivity to environmental conditions. In this study, we report a novel brevinin-1 type antimicrobial peptide B1LTe, derived from the skin secretion of Hylarana latouchii. Although the novel peptide B1LTe exhibited remarkable antimicrobial effects, its narrow therapeutic index (TI) can result in adverse drug reactions. Thus, the rational design by systematically scanning and replacing the inherent hydrophobic and cationic residues (Leucine and Lysine) with their D-enantiomeric counterparts was conducted to enhance the application potential of B1LTe. Simultaneously, we also applied lysine-to-arginine substitution within the modification. Among the derivates, 5 R demonstrated the highest selectivity and effectiveness against Methicillin-resistant Streptococcus aureus (MRSA), clinic-isolated Streptococcus pyogenes (S. pyogenes) strain, ranging from their planktonic to biofilm cells, both in vitro and in vivo. Furthermore, the remarkable adaptation of 5 R in saline and 20% serum indicates its potential for clinical application. We employed the in silico approach, which revealed the mechanism of interaction between 5 R and bacterial membranes. In addition, further mechanistic studies of 5 R elucidated the association between the collapsed proton motive force (PMF) and membrane perturbation as peptides aggregate on the bacterial membrane. Overall, our study suggests the D-enantiomeric 5 R can be a promising antibiotic agent against MDR bacteria in further clinical development and highlights the significance of cellular PMF as a potential target for the research of peptides' mode of action.

Hybrid Membrane Camouflaged Chemodrug-Gene Nanoparticles for Enhanced Combination Therapy of Ovarian Cancer.

Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.

iTRAQ-based quantitative proteomic analysis of the antibacterial mechanism of silver nanoparticles against multidrug-resistant Streptococcus suis.

Background: The increase in antibiotic resistance of bacteria has become a major concern in clinical treatment. Silver nanoparticles (AgNPs) have significant antibacterial effects against Streptococcus suis. Therefore, this study aimed to investigate the antibacterial activity and mechanism of action of AgNPs against multidrug-resistant S. suis. Methods: The effect of AgNPs on the morphology of multidrug-resistant S. suis was observed using scanning electron microscopy (SEM). Differentially expressed proteins were analyzed by iTRAQ quantitative proteomics, and the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining. Results: SEM showed that AgNPs disrupted the normal morphology of multidrug-resistant S. suis and the integrity of the biofilm structure. Quantitative proteomic analysis revealed that a large number of cell wall synthesis-related proteins, such as penicillin-binding protein and some cell cycle proteins, such as the cell division protein FtsZ and chromosomal replication initiator protein DnaA, were downregulated after treatment with 25 µg/mL AgNPs. Significant changes were also observed in the expression of the antioxidant enzymes glutathione reductase, alkyl hydroperoxides-like protein, α/ß superfamily hydrolases/acyltransferases, and glutathione disulfide reductases. ROS production in S. suis positively correlated with AgNP concentration. Conclusion: The potential antibacterial mechanism of AgNPs may involve disrupting the normal morphology of bacteria by inhibiting the synthesis of cell wall peptidoglycans and inhibiting the growth of bacteria by inhibiting the cell division protein FtsZ and Chromosomal replication initiator protein DnaA. High oxidative stress may be a significant cause of bacterial death. The potential mechanism by which AgNPs inhibit S. suis biofilm formation may involve affecting bacterial adhesion and interfering with the quorum sensing system.

A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity.

Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and anticancer potentials have been underrated compared to other peptides discovered from natural resources. Herein, a series of analogs were designed based on the template sequence of crabrolin to study its structure-activity relationship and enhance the drug's potential by changing the number, type, and distribution of charged residues. The cationicity-enhanced derivatives were shown to have improved antibacterial and anticancer activities with a lower toxicity. Notably, the double-arginine-modified product, crabrolin-TR, possessed a potent capacity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 4 µM), which was around thirty times stronger than the parent peptide (MIC = 128 µM). Furthermore, crabrolin-TR showed an in vivo treatment efficacy in a Klebsiella-pneumoniae-infected waxworm model and was non-toxic under its maximum MBC value (MIC = 8 µM), indicating its therapeutic potency and better selectivity. Overall, we rationally designed functional peptides by progressively increasing the number and distribution of charged residues, demonstrating new insights for developing therapeutic molecules from natural resources with enhanced properties, and proposed crabrolin-TR as an appealing antibacterial and anticancer agent candidate for development.

A Novel Antimicrobial Peptide, Dermaseptin-SS1, with Anti-Proliferative Activity, Isolated from the Skin Secretion of Phyllomedusa tarsius.

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a 'shotgun' cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.

Alternative splicing events and function in the tumor microenvironment: New opportunities and challenges.

Alternative splicing controls gene expression at the transcriptional level, producing structurally and functionally distinct protein heterodimers. Aberrant alternative splicing greatly affects cell development and plays an important role in the invasion and metastasis of many types of cancer. Recently, it has been shown that alternative splicing can alter the tumor microenvironment and regulate processes such as remodeling, immunity, and inflammation in the tumor microenvironment. However, there is no comprehensive literature review of the complex relationship between alternative splicing and the tumor microenvironment. Therefore, this review aims to collect all the latest data on this topic and provide a new perspective on the therapeutic and potential prognostic markers of cancer.

Discovery and analysis of a novel antimicrobial peptide B1AW from the skin secretion of Amolops wuyiensis and improving the membrane-binding affinity through the construction of the lysine-introduced analogue.

In the development and study of antimicrobial peptides (AMPs), researchers have kept a watchful eye on peptides from the brevinin family because of their extensive antimicrobial activities and anticancer potency. In this study, a novel brevinin peptide was isolated from the skin secretions of the Wuyi torrent frog, Amolops wuyiensis (A. wuyiensisi), named B1AW (FLPLLAGLAANFLPQIICKIARKC). B1AW displayed anti-bacterial activity against Gram-positive bacteria Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus faecalis (E. faecalis). B1AW-K was designed to broaden the antimicrobial spectrum of B1AW. The introduction of a lysine residue generated an AMP with enhanced broad-spectrum antibacterial activity. It also displayed the ability to inhibit the growth of human prostatic cancer PC-3, non-small lung cancer H838, and glioblastoma cancer U251MG cell lines. In molecular dynamic (MD) simulations, B1AW-K had a faster approach and adsorption to the anionic membrane than B1AW. Therefore, B1AW-K was considered a drug prototype with a dual effect, which deserves further clinical investigation and validation.

A frog-derived antimicrobial peptide as a potential anti-biofilm agent in combating Staphylococcus aureus skin infection.

Staphylococcus aureus (S. aureus), one of the most prevalent bacteria found in atopic dermatitis lesions, can induce ongoing infections and inflammation by downregulating the expression of host defence peptides in the skin. In addition, the emergence of the 'superbug' Methicillin-resistant S. aureus (MRSA) has made the treatment of these infections more challenging. Antimicrobial peptides (AMPs), due to their potent antimicrobial activity, limited evidence of resistance development, and potential immunomodulatory effects, have gained increasing attention as potential therapeutic agents for atopic dermatitis. In this study, we report a novel AMP, brevinin-1E-OG9, isolated from the skin secretions of Odorrana grahami, which shows potent antibacterial activity, especially against S. aureus. Based on the characteristics of the 'Rana Box', we designed a set of brevinin-1E-OG9 analogues to explore its structure-activity relationship. Brevinin-1E-OG9c-De-NH2 exhibited the most potent antimicrobial efficacy in both in vitro and ex vivo studies and attenuated inflammatory responses induced by lipoteichoic acid and heat-killed microbes. As a result, brevinin-1E-OG9c-De-NH2 might represent a promising candidate for the treatment of S. aureus skin infections.

Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota.

With the rising incidence of diabetes and its onset at a younger age, the impact on the male reproductive system has gradually gained attention. Exenatide is a glucagon-like peptide-1 receptor agonist effective in the treatment of diabetes. However, its role in diabetes-induced reproductive complications has rarely been reported. The study aimed to investigate the mechanism by which exenatide improved diabetic hypogonadism by regulating gut microbiota (GM) mediated inflammation. C57BL/6J mice were equally divided into normal control (NC), diabetic model control (DM) and exenatide-treated (Exe) groups. Testicular, pancreatic, colonic, and fecal samples were collected to assess microbiota, morphologic damage, and inflammation. Exenatide significantly reduced the fasting blood glucose (FBG) level in diabetic mice, increased the testosterone level, ameliorated the pathological morphological damage of islet, colon, and testes, and reduced the expression of pro-inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in colon and testis. Furthermore, exenatide significantly reduced the abundance of some pathogenic bacteria, such as Streptococcaceae and Erysipelotrichaceae, and increased that of beneficial bacteria Akkermansia. Probiotics, such as Lactobacillus were negatively correlated with TNF-α, nuclear factor-kappa-B (NF-κB), IL-6, and FBG. Conditional pathogenic bacteria such as Escherichia/Shigella Streptococcus were positively correlated with TNF-α, NF-κB, IL-6, and FBG. The fecal bacteria transplantation experiment revealed that the abundance of pathogenic bacteria, Peptostreptococcaceae, significantly decreased from Exe group mice to pseudo-sterile diabetic mice, and the pathological damage to testes was also alleviated. These data suggested the protective effects of exenatide on male reproductive damage induced by diabetes by regulating GM.

Monitoring weed mechanical and chemical damage stress based on chlorophyll fluorescence imaging.

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq'/Fm', ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.