Delivery of Encapsulated Intelligent Engineered Probiotic for Inflammatory Bowel Disease Therapy.

Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis.

Open-vessel polymerization of N-carboxyanhydride (NCA) for polypeptide synthesis.

Synthetic polypeptides, also known as poly(α-amino acids), have the same polyamide backbone structures as natural proteins and peptides. As an important class of biomaterials, polypeptides have been widely used because of their biocompatibility, bioactivity and biodegradability. Ring-opening polymerization of N-carboxyanhydride (NCA) is a classical and widely used method for the synthesis of polypeptides.

Safety evaluation of extracorporeal shockwave lithotripsy for pancreatic stones: Experience based on a large chronic pancreatitis cohort.

Background: The safety of extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and adverse events were not evaluated and classified within large sample population. This study aimed to evaluate the safety and classify the adverse events of P-ESWL based on a large sample cohort.

Methods: This is an observational study based on the large prospective chronic pancreatitis (CP) cohort.

Signature Search Polestar: a comprehensive drug repurposing method evaluation assistant for customized oncogenic signature.

Summary: The burgeoning high-throughput technologies have led to a significant surge in the scale of pharmacotranscriptomic datasets, especially for oncology. Signature search methods (SSMs), utilizing oncogenic signatures formed by differentially expressed genes through sequencing, have been instrumental in anti-cancer drug screening and identifying mechanisms of action without relying on prior knowledge. However, various studies have found that different SSMs exhibit varying performance across pharmacotranscriptomic datasets.

Recent Advances and Future Developments in the Preparation of Polypeptides via -Carboxyanhydride (NCA) Ring-Opening Polymerization.

Polypeptides have the same or similar backbone structures as proteins and peptides, rendering them as suitable and important biomaterials. Amino acid -carboxyanhydrides (NCA) ring-opening polymerization has been the most efficient strategy for polypeptide preparation, with continuous advance in the design of initiators, catalysts and reaction conditions. This Perspective first summarizes the recent progress of NCA synthesis and purification.

Long-term clinical outcomes of extracorporeal shockwave lithotripsy and endoscopic retrograde cholangiopancreatography for pancreatic duct stone treatment in patients with chronic pancreatitis.

Background And Aims: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP.

Methods: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study.

AI-guided few-shot inverse design of HDP-mimicking polymers against drug-resistant bacteria.

Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives to antibiotics and have large-scale untapped potential. Artificial intelligence (AI) exhibits promising performance on large-scale chemical-content design, however, existing AI methods face difficulties on scarcity data in each family of HDP-mimicking polymers (<10), much smaller than public polymer datasets (>10), and multi-constraints on properties and structures when exploring high-dimensional polymer space. Herein, we develop a universal AI-guided few-shot inverse design framework by designing multi-modal representations to enrich polymer information for predictions and creating a graph grammar distillation for chemical space restriction to improve the efficiency of multi-constrained polymer generation with reinforcement learning.

An Assay for Immunogenic Detection of Anti-PEG Antibody.

With the increasing use of polyethylene glycol (PEG) based proteins and drug delivery systems, anti-PEG antibodies have commonly been detected among the population, causing the accelerated blood clearance and hypersensitivity reactions, poses potential risks to the clinical efficacy and safety of PEGylated drugs. Therefore, vigilant monitoring of anti-PEG antibodies is crucial for both research and clinical guidance regarding PEGylated drugs. The enzyme-linked immunosorbent assay (ELISA) is a common method for detecting anti-PEG antibodies.

Reversing Anticancer Drug Resistance by Synergistic Combination of Chemotherapeutics and Membranolytic Antitumor β-Peptide Polymer.

Multidrug resistance is the main obstacle to cancer chemotherapy. Overexpression of drug efflux pumps causes excessive drug efflux from cancer cells, ultimately leading to drug resistance. Hereby, we raise an effective strategy to overcome multidrug resistance using a synergistic combination of membranolytic antitumor β-peptide polymer and chemotherapy drugs.

A dual-targeting antifungal is effective against multidrug-resistant human fungal pathogens.

Drug-resistant fungal infections pose a significant threat to human health. Dual-targeting compounds, which have multiple targets on a single pathogen, offer an effective approach to combat drug-resistant pathogens, although ensuring potent activity and high selectivity remains a challenge. Here we propose a dual-targeting strategy for designing antifungal compounds.

ApoE-functionalization of nanoparticles for targeted brain delivery-a feasible method for polyplexes?

The blood-brain barrier (BBB) poses a major obstacle in the treatment of all types of central nervous system (CNS) diseases. Small interfering RNA (siRNA) offers in principle a promising therapeutic approach by downregulating disease-related genes via RNA interference. However, the BBB is a formidable barrier for macromolecules such as nucleic acids.

Peptide-Mimicking Poly(2-oxazoline)s Possessing Potent Antifungal Activity and BBB Penetrating Property to Treat Invasive Infections and Meningitis.

Invasive fungal infections, including meningitis, cause a high mortality rate due to few available antifungal drugs and frequently associated side effects and quick emergence of drug-resistant fungi. The restrictive permeability of the blood-brain barrier (BBB) further limits the efficacy of antifungal agents substantially in treating meningitis. Hereby, we design and synthesize guanidinium-functionalized poly(2-oxazoline)s by mimicking cell-penetrating peptides.

Facile Construction of Antimicrobial Surface via One-Step Co-Deposition of Peptide Polymer and Dopamine.

The infections associated with implantable medical devices can greatly affect the therapeutic effect and impose a heavy financial burden. Therefore, it is of great significance to develop antimicrobial biomaterials for the prevention and mitigation of healthcare-associated infections. Here, a facile construction of antimicrobial surface via one-step co-deposition of peptide polymer and dopamine is reported.

Universal and One-Step Modification to Render Diverse Materials Bioactivation.

Bioactive materials that can support cell adhesion and tissue regeneration are greatly in demand in clinical applications. Surface modification with bioactive molecules is an efficient strategy to convert conventional bioinert materials into bioactive materials. However, there is an urgent need to find a universal and one-step modification strategy to realize the above transformation for bioactivation.

Convenient and Controllable Synthesis of Poly(2-oxazoline)-Conjugated Doxorubicin for Regulating Anti-Tumor Selectivity.

Polyethylene glycol (PEG)-doxorubicin (DOX) conjugation is an important strategy to improve toxicity and enhance clinically therapeutic efficacy. However, with the frequent use of PEG-modified drugs, the accumulation of anti-PEG antibodies has become a tough issue, which limits the application of PEG-drug conjugation. As an alternative solution, poly(2-oxazoline) (POX)-DOX conjugation has shown great potential in the anti-tumor field, but the reported conjugation process of POX with DOX has drawbacks such as complex synthetic steps and purification.

Protein corona investigations of polyplexes with varying hydrophobicity - From method development to in vitro studies.

In the field of non-viral drug delivery, polyplexes (PXs) represent an advanced investigated and highly promising tool for the delivery of nucleic acids. Upon encountering physiological fluids, they adsorb biological molecules to form a protein corona (PC), that influence PXs biodistribution, transfection efficiencies and targeting abilities. In an effort to understand protein - PX interactions and the effect of PX material on corona composition, we utilized cationic branched 10 kDa polyethyleneimine (b-PEI) and a hydrophobically modified nylon-3 polymer (NM/CP) within this study to develop appropriate methods for PC investigations.

Direct Identification and Quantitation of Protein Peptide Powders Based on Multi-Molecular Infrared Spectroscopy and Multivariate Data Fusion.

Given that protein peptide powders (PPPs) from different biological sources were inherited with diverse healthcare functions, which aroused adulteration of PPPs. A high-throughput and rapid methodology, united multi-molecular infrared (MM-IR) spectroscopy with data fusion, could determine the types and component content of PPPs from seven sources as examples. The chemical fingerprints of PPPs were thoroughly interpreted by tri-step infrared (IR) spectroscopy, and the defined spectral fingerprint region of protein peptide, total sugar, and fat was 3600-950 cm, which constituted MIR finger-print region.

Integrated network pharmacology and fecal metabolomic analysis of the combinational mechanisms of Shexiang Baoxin Pill against atherosclerosis.

Shexiang Baoxin Pill (SBP) has an excellent therapeutic effect on atherosclerosis (AS), but the combinational mechanisms of SBP against AS remain unclear. This study aimed to investigate the combinational mechanisms of SBP against AS by comprehensive network pharmacology and fecal metabolomic analysis. , one of the adjuvant medicines in SBP, is an animal medicine with a narrow therapeutic window.

Host-Defense-Peptide-Mimicking β-Peptide Polymer Acting as a Dual-Modal Antibacterial Agent by Interfering Quorum Sensing and Killing Individual Bacteria Simultaneously.

Host defense peptides (HDPs) are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate, but their clinical applications are limited by proteolytic instability, high-cost, and complicated synthesis process. Here, we report a host-defense-peptide-mimicking β-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions, excellent antimicrobial efficiency even at high density of bacteria, and low cost for preparation. The β-peptide polymer demonstrated quorum sensing (QS) interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes.

Switching from membrane disrupting to membrane crossing, an effective strategy in designing antibacterial polypeptide.

Drug-resistant bacterial infections have caused serious threats to human health and call for effective antibacterial agents that have low propensity to induce antimicrobial resistance. Host defense peptide-mimicking peptides are actively explored, among which poly-β-l-lysine displays potent antibacterial activity but high cytotoxicity due to the helical structure and strong membrane disruption effect. Here, we report an effective strategy to optimize antimicrobial peptides by switching membrane disrupting to membrane penetrating and intracellular targeting by breaking the helical structure using racemic residues.

Advance in the Polymerization Strategy for the Synthesis of β-Peptides and β-Peptoids.

Peptide mimics, possessing excellent biocompatibility and protease stability, have attracted broad attention and research in the biomedical field. β-Peptides and β-peptoids, as two types of vital peptide mimics, have demonstrated great potential in the field of foldamers, antimicrobials and protein binding, etc. Currently, the main synthetic strategies for β-peptides and β-peptoids include solid-phase synthesis and polymerization.

Ginsenoside Rc ameliorated atherosclerosis regulating gut microbiota and fecal metabolites.

Atherosclerosis (AS) and the accompanied cardiovascular diseases (CVDs) were the leading cause of death worldwide. Recently, the association between CVDs, gut microbiota, and metabolites had aroused increasing attention. In the study, we headed our investigation into the underlying mechanism of ginsenoside Rc (GRc), an active ingredient of ginsenosides used for the treatment of CVDs, in apolipoprotein E-deficient (ApoE) mice with high-fat diet (HFD).

A Polymeric Strategy Empowering Vascular Cell Selectivity and Potential Application Superior to Extracellular Matrix Peptides.

Endothelialization of vascular implants plays a vital role in maintaining the long-term vascular patency. In situ endothelialization and re-endothelialization is generally achieved by selectively promoting endothelial cell (EC) adhesion and, meanwhile, suppressing smooth muscle cell (SMC) adhesion. Currently, such EC versus SMC selectivity is achieved and extensively used in vascular-related biomaterials utilizing extracellular-matrix-derived EC-selective peptides, dominantly REDV and YIGSR.

Advance and Designing Strategies in Polymeric Antifungal Agents Inspired by Membrane-Active Peptides.

The high-mortality invasive fungal infections seriously threaten the lives of immunocompromised people. Host defense peptides and cell-penetrating peptides are representative membrane-active peptides with different functions. Among them, host defense peptides mimicking is a valid strategy in the design of synthetic antifungal agents.