A Lipid with Lewis Pair-Mediated Targeting and Multiple Stimuli-Responsive Delivery of Antibiotics for Bacterial Infections.

Integrating both targeted delivery and stimulus-responsive release into a single small molecule for drug delivery presents challenges related to synthesis, stability, and efficacy. In this study, single-molecular lipids incorporating a Lewis pair (Lp-lipids) are described, composed of a Lewis acid (phenylboronic acid) and a Lewis base (amine) within a single small molecular structure, to formulate lipid nanoparticles for antibiotic delivery. For targeted delivery to bacterial biofilms, the phenylboronic acid selectively binds to bacteria or biofilms by forming boronate ester bonds with diols in the microbial dextran or peptidoglycan.

A bacteriophage protein-driven platform for rapid and precise diagnosis of bacterial pathogens from blood samples.

The rapid emergence of antibiotic-resistant pathogens underscores the urgent need for fast, accurate, and accessible diagnostics to guide targeted therapy and mitigate resistance. Conventional methods for identifying bacterial infections are slow, labor-intensive, and costly, necessitating alternative approaches. Here, we developed an integrated diagnostic platform that employs bacteriophage-derived receptor-binding proteins (RBPs) and endolysin cell wall-binding domains (CBDs) for rapid bloodstream pathogen detection.

Quaternized chitosan-coated PLGA nanoparticles co-deliver resveratrol and all-trans retinoic acid to enhance humoral immunity, cellular immunity and gastrointestinal mucosal immunity.

Conventional vaccine adjuvants are limited by their mechanisms of action and administration routes, often failing to simultaneously elicit robust systemic and mucosal immune responses. This limitation compromises the establishment of dual protective barriers during early pathogen invasion. Therefore, we developed an innovative poly (lactic-co-glycolic acid) (PLGA) nanoparticle-based adjuvant system (Res/RA QCS NPs) featuring quaternized chitosan (QCS) surface modification for ovalbumin (OVA) delivery, co-encapsulating dual immunomodulators - resveratrol (Res) and all-trans retinoic acid (RA).

AmpHGT: expanding prediction of antimicrobial activity in peptides containing non-canonical amino acids using multi-view constrained heterogeneous graph transformer.

Background: Antimicrobial peptide (AMP) prediction has been extensively studied in recent years. However, many existing models do not fully leverage the intrinsic chemical structures of AMPs, such as atomic composition and sidechain group characteristics. Instead, these models often focus on letter composition, positional encodings, and pre-defined chemical-physical descriptors.

Rhein restores the sensitivity of carrying multidrug-resistant to colistin.

The emergence of the colistin resistance gene has resulted in a significant reduction in the clinical efficacy of colistin against infections caused by multidrug-resistant Gram-negative pathogens. A cost-effective approach for restoring the efficacy of antibiotics is to formulate synergistic antibiotic combinations with natural compounds that target the resistance of multidrug-resistant bacteria. In this study, we have demonstrated that rhein can effectively restore the sensitivity of -positive to colistin, both and .

Enhanced mucosal immune response through nanoparticle delivery system based on chitosan-catechol and a recombinant antigen targeted towards M cells.

In mucosal vaccination, the targeted delivery of antigens through M (microfold) cells is essential for initiating a robust antigen-specific immune response. In the present study, we devised a nano-delivery platform to target M cells. This platform involved coating mesoporous silica nanoparticles (MSN) with a mucoadhesive chitosan-catechol (Chic) layer, incorporating a recombinant antigen to form nanoparticles that enhance the immune response.

Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies.

The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic-resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bactericidal activity through a mechanism distinct from that of clinically used antibiotics.

Engineered Hybrid Lantibiotic that Selectively Combats Infections Caused by .

The rapid emergence of antibiotic-resistant strains of presents a substantial challenge to global public health, underscoring the urgent need for novel antibiotics with diverse mechanisms of action. In this study, we conducted mutagenesis on the -terminal region of the lantibiotic ripcin C to enhance its antimicrobial efficacy against . The resulting optimized variant, ripcin C, demonstrated potent and selective antimicrobial activity, with a minimal inhibitory concentration of 2-4 mg/L against .

Myricetin inhibits transmissible gastroenteritis virus replication by targeting papain-like protease deubiquitinating enzyme activity.

Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This α-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination.

Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance.

Polymyxins have been regarded as an efficient therapeutic against many life-threatening, multidrug resistant Gram-negative bacterial infections; however, the cytotoxicity and emergence of drug resistance associated with polymyxins have greatly hindered their clinical potential. Herein, the reaction-induced self-assembly (RISA) of polymyxins and natural aldehydes in aqueous solution is presented. The resulting assemblies effectively mask the positively charged nature of polymyxins, reducing their cytotoxicity.

Guiding antibiotics towards their target using bacteriophage proteins.

Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity.

Pathogen-Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization.

Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan-catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions.

Gallnut tannic acid alleviates gut damage induced by in broilers by enhancing barrier function and modulating microbiota.

Pullorum disease (PD) is a bacterial infection caused by () that affects poultry. It is highly infectious and often fatal. Antibiotics are currently the mainstay of prophylactic and therapeutic treatments for PD, but their use can lead to the development of resistance in pathogenic bacteria and disruption of the host's intestinal flora.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II.

Rat Hepatocytes Protect against Lead-Cadmium-Triggered Apoptosis Based on Autophagy Activation.

Lead and cadmium are foodborne contaminants that threaten human and animal health. It is well known that lead and cadmium produce hepatotoxicity; however, defense mechanisms against the co-toxic effects of lead and cadmium remain unknown. We investigated the mechanism of autophagy (defense mechanism) against the co-induced toxicity of lead and cadmium in rat hepatocytes (BRL-3A cells).

A supramolecular hydrogel dressing with antibacterial, immunoregulation, and pro-regeneration ability for biofilm-associated wound healing.

Chronic wound treatment has emerged as a significant healthcare concern worldwide due to its substantial economic burden and the limited effectiveness of current treatments. Effective management of biofilm infections, regulation of excessive oxidative stress, and promotion of tissue regeneration are crucial for addressing chronic wounds. Hydrogel stands out as a promising candidate for chronic wound treatment.

Brevicidine acts as an effective sensitizer of outer membrane-impermeable conventional antibiotics for treatment.

The antibiotic resistance of poses a significant threat to global public health, especially those strains that are resistant to carbapenems. Therefore, novel strategies are desperately needed for the treatment of infections caused by antibiotic-resistant . In this study, we report that brevicidine, a bacterial non-ribosomally produced cyclic lipopeptide, shows synergistic effects with multiple outer membrane-impermeable conventional antibiotics against .

Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway.

Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug.

Seeing the Invisibles: Detection of Peptide Enantiomers, Diastereomers, and Isobaric Ring Formation in Lanthipeptides Using Nanopores.

Mass spectrometry (MS) is widely used in proteomic analysis but cannot differentiate between molecules with the same mass-to-charge ratio. Nanopore technology might provide an alternative method for the rapid and cost-effective analysis and sequencing of proteins. In this study, we demonstrate that nanopore currents can distinguish between diastereomeric and enantiomeric differences in l- and d-peptides, not observed by conventional MS analysis, down to individual d-amino acids in small opioid peptides.

Burkill alleviates LPS/D-GalN-induced acute liver failure by modulating apoptosis and oxidative stress signaling pathways.

Burkill is widely distributed along the southwestern region of China. It is known as "Dida" in Tibetan and "Qingyedan" in Chinese medicine. It was used in folk medicine to treat hepatitis and other liver diseases.

Preparation, characterization and protective effect of chitosan - Tripolyphosphate encapsulated dihydromyricetin nanoparticles on acute kidney injury caused by cisplatin.

Dihydromyricetin (DMY) is a natural dihydroflavonol compound known for its diverse pharmacological benefits. However, its limited stability and bioavailability posed significant challenges for further applications. To address these issues, in this study, an ion crosslinking method was utilized to prepare chitosan nanoparticles that were loaded with DMY.

Exosomes from tannic acid-stimulated macrophages accelerate wound healing through miR-221-3p mediated fibroblasts migration by targeting CDKN1b.

Tannic acid (TA) and its extraction were traditionally used for treatment of traumatic bleeding in China, and in the previous study we have demonstrated that TA could accelerate cutaneous wound healing in rats. We attempted to decipher the mechanism of TA in promoting wound healing. In this study, we found that TA could enhance the growth of macrophages and inhibit the release of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8 and IL-10) through inhibition of NF-κB/JNK pathway.