A parametric study of motion and attachment to capillary walls of circulating tumor cells (CTCs) interacting with non-activated and activated platelets.

Background And Objective: Our previous research examined the biophysical conditions required for CTC arrest using a custom-built solid-fluid 2D axisymmetric computational model. Application of that model resulted in calculating the limiting conditions under which a CTC can pass through a narrowed capillary with a platelet attached to the capillary wall. This paper is a step forward in determining the effects of a selected set of parameters: number of platelets, CTC diameter, stiffness, and ligand-receptor bond stiffness of the CTC (with or without attached platelets) on the CTC trajectory, its axial position, and its attachment to the wall.

Developing 3D bioprinting for organs-on-chips.

Organs-on-chips (OoCs) have significantly advanced biomedical research by precisely reconstructing human microphysiological systems with biomimetic functions. However, achieving greater structural complexity of cell cultures on-chip for enhanced biological mimicry remains a challenge. To overcome these challenges, 3D bioprinting techniques can be used in directly building complex 3D cultures on chips, facilitating the engineering of organ-level models.

Research progress on human papillomavirus-negative cervical cancer: A review.

Cervical cancer is the fourth most common cancer in women worldwide. The vast majority of cervical cancers are associated with human papillomavirus (HPV) infection, but a small proportion of cervical cancers occur independently of HPV infection, with different subtypes having varying rates of occurrence. Despite the presence of false negatives in current testing, improving the accuracy of detection is crucial for studying the pathogenesis of HPV-negative cervical cancer and improving the prognosis of these patients.

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.

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.

Rapid and Accurate Detection of SARS-CoV-2 Using an iPad-Controlled, High-Throughput, Portable, and Multiplex ve-Chip Platform (Cube).

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most effective measures to control the coronavirus disease 2019 (COVID-19) pandemic. However, there is still lack of an ideal detection platform capable of high sample throughput, portability, and multiplicity. Herein, by combining Hive-Chip (capillary microarray) and reverse transcriptional loop-mediated isothermal amplification (RT-LAMP), we developed an iPad-controlled, high-throughput (48 samples at one run), portable (smaller than a backpack), multiplex (monitoring 8 gene fragments in one reaction), and real-time detection platform for SARS-CoV-2 detection.

Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis.

Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH-NADPH-SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore.

A Bidirectional Single-Cell Migration and Retrieval Chip for Quantitative Study of Dendritic Cell Migration.

Dendritic cell (DC) migration is a fundamental step during execution of its adaptive immunity functions. Studying DC migration characteristics is critical for development of DC-dependent allergy treatments, vaccines, and cancer immunotherapies. Here, a microfluidics-based single-cell migration platform is described that enables high-throughput and precise bidirectional cell migration assays.

Development and validation of a novel immunotype for prediction of overall survival in patients with clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor. The purpose of the present study was to establish a novel immunotype for different immune infiltration and overall survival (OS) of patients with ccRCC.

Methods: Based on the Cancer Genome Atlas Project (TCGA) database (discovery set), a novel immunotype was established using ssGSEA methods.

Biodegradable peptide polymers as alternatives to antibiotics used in aquaculture.

The pressure of antimicrobial resistance has forced many countries to reduce or even prohibit the use of antibiotics in feed. Therefore, it is an urgent need to develop alternatives to antibiotics to control infectious diseases in feed and aquaculture. To address this long-lasting challenge, we prepared peptide polymers that display potent and broad-spectrum activity against common pathogenic bacteria in aquaculture, low hemolysis and low cytotoxicity, and do not induce bacteria to develop resistance or cross-resistance to antibiotics.

An Effective Strategy to Develop Potent and Selective Antifungal Agents from Cell Penetrating Peptides in Tackling Drug-Resistant Invasive Fungal Infections.

The high mortality rate of invasive fungal infections and quick emergence of drug-resistant fungal pathogens urgently call for potent antifungal agents. Inspired by the cell penetrating peptide (CPP) octaarginine (R8), we elongated to 28 residues poly(d,l-homoarginine) to obtain potent toxicity against both fungi and mammalian cells. Further incorporation of glutamic acid residues shields positive charge density and introduces partial zwitterions in the obtained optimal peptide polymer that displays potent antifungal activity against drug-resistant fungi superior to antifungal drugs, excellent stability upon heating and UV exposure, negligible and toxicity, and strong therapeutic effects in treating invasive fungal infections.

Heterochiral β-Peptide Polymers Combating Multidrug-Resistant Cancers Effectively without Inducing Drug Resistance.

Multidrug resistance to chemotherapeutic drugs is one of the major causes for the failure of cancer treatment. Therefore, there is an urgent need to develop anticancer agents that can combat multidrug-resistant cancers effectively and mitigate drug resistance. Here, we report a rational design of anticancer heterochiral β-peptide polymers as synthetic mimics of host defense peptides to combat multidrug-resistant cancers.

Microbial Metabolite Inspired β-Peptide Polymers Displaying Potent and Selective Antifungal Activity.

Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL-diaminopropionic acid) (PDAP) from the ring-opening polymerization of β-amino acid N-thiocarboxyanhydrides, by mimicking ε-poly-lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis.

Short Guanidinium-Functionalized Poly(2-oxazoline)s Displaying Potent Therapeutic Efficacy on Drug-Resistant Fungal Infections.

New antifungals are urgently needed to combat invasive fungal infections, due to limited types of available antifungal drugs and frequently encountered side effects, as well as the quick emergence of drug-resistance. We previously developed amine-pendent poly(2-oxazoline)s (POXs) as synthetic mimics of host defense peptides (HDPs) to have antibacterial properties, but with poor antifungal activity. Hereby, we report the finding of short guanidinium-pendent POXs, inspired by cell-penetrating peptides, as synthetic mimics of HDPs to display potent antifungal activity, superior mammalian cells versus fungi selectivity, and strong therapeutic efficacy in treating local and systemic fungal infections.

Secondary Amine Pendant β-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs.

A Cryptic Palmitoyl Chain Involved in Safracin Biosynthesis Facilitates Post-NRPS Modifications.

This study confirmed the participation of a cryptic palmitoyl fatty acyl chain in the biosynthesis of safracin and unraveled a previously ignored peptidase for the removal of the precursor. Furthermore, the post-assembly line tailoring steps are extensively studied in terms of the methyltransferase SacI-catalyzed N-methylation and the FAD-dependent monooxygenase SacJ-catalyzed A-ring oxidation. The timing of these post-NRPS steps is also addressed in this work.

Addressing MRSA infection and antibacterial resistance with peptoid polymers.

Methicillin-Resistant Staphylococcus aureus (MRSA) induced infection calls for antibacterial agents that are not prone to antimicrobial resistance. We prepare protease-resistant peptoid polymers with variable C-terminal functional groups using a ring-opening polymerization of N-substituted N-carboxyanhydrides (NNCA), which can provide peptoid polymers easily from the one-pot synthesis. We study the optimal polymer that displays effective activity against MRSA planktonic and persister cells, effective eradication of highly antibiotic-resistant MRSA biofilms, and potent anti-infectious performance in vivo using the wound infection model, the mouse keratitis model, and the mouse peritonitis model.

Superfast and Water-Insensitive Polymerization on α-Amino Acid N-Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator.

We design the tetraalkylammonium carboxylate-initiated superfast polymerization on α-amino acid N-carboxyanhydrides (NCA) for efficient synthesis of polypeptides. Carboxylates, as a new class of initiator for NCA polymerization, can initiate the superfast NCA polymerization without the need of extra catalysts and the polymerization can be operated in open vessels at ambient condition without the use of glove box. Tetraalkylammonium carboxylate-initiated polymerization on NCA easily affords block copolymers with at least 15 blocks.

Recent Advances in Microfluidic Platforms for Programming Cell-Based Living Materials.

Cell-based living materials, including single cells, cell-laden fibers, cell sheets, organoids, and organs, have attracted intensive interests owing to their widespread applications in cancer therapy, regenerative medicine, drug development, and so on. Significant progress in materials, microfabrication, and cell biology have promoted the development of numerous promising microfluidic platforms for programming these cell-based living materials with a high-throughput, scalable, and efficient manner. In this review, the recent progress of novel microfluidic platforms for programming cell-based living materials is presented.

The membrane-targeting mechanism of host defense peptides inspiring the design of polypeptide-conjugated gold nanoparticles exhibiting effective antibacterial activity against methicillin-resistant .

Multidrug-resistant bacterial infections are a grand challenge to global medical and health systems. Therefore, it is urgent to develop versatile antibacterial strategies that can combat bacterial resistance without displaying toxicity. Here, we synthesize antibacterial polypeptide-conjugated gold nanoparticles that exhibit potent antibacterial activities against clinically isolated multiple drug resistance Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus, and excellent in vitro and in vivo biocompatibility.