Berberine‑calcium alginate-coated macrophage membrane-derived nanovesicles for the oral treatment of ulcerative colitis.

In this study, we developed calcium alginate-coated nanovesicles derived from macrophage membranes loaded with berberine (Ber@MVs-CA) for the oral treatment of ulcerative colitis (UC). Ber@MVs-CA demonstrates resistance to gastric acid and controlled drug release in the colonic pH environment, while actively targeting sites of ulcerative colitis injury. pH-responsive release of Ber in Ber@MVs-CA was confirmed through in vitro release experiments.

Single organic electrode for multi-system dual-ion symmetric batteries.

The large void space of organic electrodes endows themselves with the capability to store different counter ions without size concern. In this work, a small-molecule organic bipolar electrode called diquinoxalino[2,3-a:2',3'-c]phenazine-2,6,10-tris(phenoxazine) (DQPZ-3PXZ) is designed. Based on its robust solid structure by the π conjugation of diquinoxalino[2,3-a:2',3'-c]phenazine (DQPZ) and phenoxazine (PXZ), DQPZ-3PXZ can indiscriminately and stably host 5 counter ions with different charge and size (Li, Na, K, PF and FSI).

Preparation of Biomimetic Selenium-Baicalein Nanoparticles and Their Targeted Therapeutic Application in Nonsmall Cell Lung Cancer.

In this study, we prepared bionic selenium-baicalein nanoparticles (ACM-SSe-BE) for the targeted treatment of nonsmall cell lung cancer. Due to the coating of the A549 membrane, the system has homologous targeting capabilities, allowing for the preparation of target tumor cells. The borate ester bond between selenium nanoparticles (SSe) and baicalein (BE) is pH-sensitive and can break under acidic conditions in the tumor microenvironment to achieve the targeted release of BE at the tumor site.

A dual-target SPR screening system for simultaneous ligand discovery of SARS-CoV-2 spike protein and its receptor ACE2 from Chinese herbs.

Traditional Chinese Medicine (TCM) is a supremely valuable resource for the development of drug discovery. Few methods are capable of hunting for potential molecule ligands from TCM towards more than one single protein target. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed to perform targeted compound screening of two key proteins involved in the cellular invasion process of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): the spike (S) protein receptor binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2).

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype.

CMNet: deep learning model for colon polyp segmentation based on dual-branch structure.

Purpose: Colon cancer is one of the top three diseases in gastrointestinal cancers, and colon polyps are an important trigger of colon cancer. Early diagnosis and removal of colon polyps can avoid the incidence of colon cancer. Currently, colon polyp removal surgery is mainly based on artificial-intelligence (AI) colonoscopy, supplemented by deep-learning technology to help doctors remove colon polyps.

Micropore-Forming Gelatin Methacryloyl (GelMA) Bioink Toolbox 2.0: Designable Tunability and Adaptability for 3D Bioprinting Applications.

It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen.

Application oriented bioaugmentation processes: Mechanism, performance improvement and scale-up.

Bioaugmentation is an optimization method with great potential to improve the treatment effect by introducing specific strains into the biological treatment system. In this study, a comprehensive review of the mechanism of bioaugmentation from the aspect of microbial community structure, the optimization methods facilitating application as well as feasible approaches of scale-up application has been provided. The different contribution of indigenous and exogenous strains was critically analyzed, the relationship between microbial community variation and system performance was clarified.

Quantitative Systems Pharmacology Modeling of PBMC-Humanized Mouse to Facilitate Preclinical Immuno-oncology Drug Development.

Progress in immunotherapy has resulted in explosively increased new therapeutic interventions and they have shown promising results in the treatment of cancer. Animal testing is performed to provide preliminary efficacy and safety data for drugs under development prior to clinical trials. However, translational challenges remain for preclinical studies such as study design and the relevance of animal models to humans.

Quantitative systems pharmacology model predictions for efficacy of atezolizumab and nab-paclitaxel in triple-negative breast cancer.

Background: Immune checkpoint blockade therapy has clearly shown clinical activity in patients with triple-negative breast cancer, but less than half of the patients benefit from the treatments. While a number of ongoing clinical trials are investigating different combinations of checkpoint inhibitors and chemotherapeutic agents, predictive biomarkers that identify patients most likely to benefit remains one of the major challenges. Here we present a modular quantitative systems pharmacology (QSP) platform for immuno-oncology that incorporates detailed mechanisms of immune-cancer cell interactions to make efficacy predictions and identify predictive biomarkers for treatments using atezolizumab and nab-paclitaxel.

Development of the computational antibiotic screening platform (CLASP) to aid in the discovery of new antibiotics.

Bacterial colonization of biotic and abiotic surfaces and antibiotic resistance are grand challenges with paramount societal impacts. However, in the face of increasing bacterial resistance to all known antibiotics, efforts to discover new classes of antibiotics have languished, creating an urgent need to accelerate the antibiotic discovery pipeline. A major deterrent in the discovering of new antibiotics is the limited permeability of molecules across the bacterial envelope.

High-Level Antibiotic Tolerance of a Clinically Isolated Enterococcus faecalis Strain.

Bacteria can survive antibiotic treatment both by acquiring antibiotic resistance genes and through mechanisms of tolerance that are based on phenotypic changes and the formation of metabolically inactive cells. Here, we report an strain ( UM001B) that was isolated from a cystic fibrosis patient and had no increase in resistance but extremely high-level tolerance to ampicillin, vancomycin, and tetracycline. Specifically, the percentages of cells that survived 3.

Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model.

Background: T cells have been recognized as core effectors for cancer immunotherapy. How to restore the anti-tumor ability of suppressed T cells or improve the lethality of cytotoxic T cells has become the main focus in immunotherapy. Bispecific antibodies, especially bispecific T cell engagers (TCEs), have shown their unique ability to enhance the patient's immune response to tumors by stimulating T cell activation and cytokine production in an MHC-independent manner.

QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.

Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune-related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently, complex, whole-body, quantitative systems pharmacology (QSP) models have become increasingly popular for discovery and development. QSP modeling has the potential to discover novel predictive biomarkers as well as test the efficacy of treatment plans and combination therapies through virtual clinical trials.

A Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor.

Cancer immunotherapy has recently drawn remarkable attention as promising results in the clinic have shown its ability to improve the overall survival, and T cells are considered to be one of the primary effectors for cancer immunotherapy. Enhanced and restored T cell tumoricidal activity has shown great potential for killing cancer cells. Bispecific T cell engagers (TCEs) are a growing class of molecules that are designed to bind two different antigens on the surface of T cells and cancer cells to bring them in close proximity and selectively activate effector T cells to kill target cancer cells.

Interaction of amphiphilic coumarin with DPPC/DPPS lipid bilayer: effects of concentration and alkyl tail length.

In this work, interactions between amphiphilic amino methyl coumarin and dipalmitoyl-sn-glycero-3-phosphocholine/dipalmitoyl-sn-glycero-3-phosphoserine (DPPC/DPPS) lipid bilayer were investigated. A combination of experimental techniques (zeta potential, fluorescence spectroscopy, and differential scanning calorimetry) along with molecular dynamics simulations was employed to examine the influence of alkyl tail length and concentration of the amphiphilic coumarin on the lipid bilayer. Alkyl tails comprising 5(C), 9(C), and 12(C) carbon atoms were conjugated to amino methyl coumarin via a single-step process.

The Influence of Water on Choline-Based Ionic Liquids.

Choline and geranic acid (CAGE)-based ionic liquids have been recently developed for applications in drug delivery. Understanding the microscopic structures of CAGE in the presence of water is critical for its continued use in biomedical applications as it will undoubtedly come into contact with water in physiological fluids. Water can drastically impact the physicochemical properties of the ionic liquids, including CAGE.

Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE).

The continued emergence of antibiotic-resistant organisms has severely depleted our arsenal of effective antimicrobials. Ionic liquids (ILs) show great promise as antibacterial agents but understanding the mechanism of attack on bacterial cells is key to ensuring that design of IL-based biocides impart maximum efficacy with minimal toxicity, while also avoiding the potential for the target organisms to become resistant. Here we report the antibacterial attributes of a set of choline and geranate (CAGE)-based ILs and identify the mechanism by which they interact with the Gram-negative cell wall of .

Dynamics of OmpF Trimer Formation in the Bacterial Outer Membrane of Escherichia coli.

The self-assembly of outer membrane protein F (OmpF) in the outer membrane of Escherichia coli Gram-negative bacteria was studied using multiscale molecular dynamics simulations. To accommodate the long time scale required for protein assembly, coarse-grained parametrization of E. coli outer membrane lipids was first developed.

Modeling Diversity in Structures of Bacterial Outer Membrane Lipids.

Lipopolysaccharides (LPSs) are vital components of the outer membrane of Gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A, a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structures and their immunogenic potencies.

Simulating Gram-Negative Bacterial Outer Membrane: A Coarse Grain Model.

The cell envelope of Gram-negative bacteria contains a lipopolysaccharide (LPS) rich outer membrane that acts as the first line of defense for bacterial cells in adverse physical and chemical environments. The LPS macromolecule has a negatively charged oligosaccharide domain that acts as an ionic brush, limiting the permeability of charged chemical agents through the membrane. Besides the LPS, the outer membrane has radially extending O-antigen polysaccharide chains and β-barrel membrane proteins that make the bacterial membrane physiologically unique compared to phospholipid cell membranes.