Macrophage manufacturing and engineering with 5'-Cap1 and N1-methylpseudouridine-modified mRNA.

Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA.

A critical time window for leukapheresis product transportation to manufacture clinical-grade dendritic cells with optimal anti-tumor activities.

Background Aims: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer. However, key aspects governing the reproducible manufacturing of high-quality DC remain incompletely defined. Here, we show that the time window between leukapheresis and DC manufacturing is critical.

A Convex Optimization Approach to Multi-Robot Task Allocation and Path Planning.

In real-world applications, multiple robots need to be dynamically deployed to their appropriate locations as teams while the distance cost between robots and goals is minimized, which is known to be an NP-hard problem. In this paper, a new framework of team-based multi-robot task allocation and path planning is developed for robot exploration missions through a convex optimization-based distance optimal model. A new distance optimal model is proposed to minimize the traveled distance between robots and their goals.

Development of a personalized dendritic cell vaccine and single-cell RNA sequencing-guided assessment of its cell type composition.

Background Aims: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective.

Methods: We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720).

A colorimetric chemical tongue detects and distinguishes between multiple analytes.

The rate-limiting step for diagnostics development is the discovery and validation of biomarker analytes. We describe a new analyte-agnostic and label-free approach based on colorimetric reactions involving type I polymerization photoinitiators. We demonstrate that a chemically diverse array of hydrogels embedded with cleaved type I photoinitiators could act as microreactors, undergoing colorimetric reactions with bound analytes.

Deep Learning-Based Complete Coverage Path Planning With Re-Joint and Obstacle Fusion Paradigm.

With the introduction of autonomy into the precision agriculture process, environmental exploration, disaster response, and other fields, one of the global demands is to navigate autonomous vehicles to completely cover entire unknown environments. In the previous complete coverage path planning (CCPP) research, however, autonomous vehicles need to consider mapping, obstacle avoidance, and route planning simultaneously during operating in the workspace, which results in an extremely complicated and computationally expensive navigation system. In this study, a new framework is developed in light of a hierarchical manner with the obtained environmental information and gradually solving navigation problems layer by layer, consisting of environmental mapping, path generation, CCPP, and dynamic obstacle avoidance.

Identification of Potential Molecular Determinants of Murine Embryonic Stem Cell Differentiation by a Transposon-Based Approach.

Embryonic stem cells (ESCs) are self-renewing pluripotent cells, capable of differentiating into all somatic cell types. The molecular control of self-renewal is relatively well-characterized, whereas how ESCs exit pluripotent state to differentiate is poorly understood. Here we identify two genes are required for differentiation and dozens of intergenic regions that potentially regulate ESC differentiation.

Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation.

The assembly of prereplicative complex (pre-RC) during G1 phase must be tightly controlled to sustain cell proliferation and maintain genomic stability. Mechanisms to prevent pre-RC formation in G2/M and S phases are well appreciated, whereas how cells ensure efficient pre-RC assembly during G1 is less clear. Here we report that cyclin K regulates pre-RC formation.

Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer.

Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations.

Chemotherapy-induced changes in cardiac capillary permeability measured by fluorescent multiple indicator dilution.

Anthracyclines cause severe irreversible cardiac toxicity. The study of changes in cardiac permeability with chemotherapy could enhance the understanding of mechanisms behind cardiac damage, and provide useful information to evaluate anthracycline cardiotoxicity. Thirty-six rats (12 Sprague-Dawley, 12 Wistar, 12 Fischer-344) were randomly assigned to control (n = 21) or doxorubicin (n = 15), and injected i.

A distinct expression pattern of cyclin K in mammalian testes suggests a functional role in spermatogenesis.

Germ cell and embryonic stem cells are inextricably linked in many aspects. Remarkably both can generate all somatic cell types in organisms. Yet the molecular regulation accounting for these similarities is not fully understood.

Thermal and pH Sensitive Multifunctional Polymer Nanoparticles for Cancer Imaging and Therapy.

In this study, we prepared novel poly(Glycerol malate co-dodecanedioate) (PGMD) NPs containing an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The PGMD polymer was prepared by thermal condensation. IR820 and DOX loaded PGMD NPs were prepared using the single oil emulsion technique.

Targeted nanoparticles for simultaneous delivery of chemotherapeutic and hyperthermia agents--an in vitro study.

The purpose of this study was to prepare targeted Poly lactide-co-glycolide (PLGA) nanoparticles with simultaneous entrapment of indocyanine green (ICG) and doxorubicin (DOX) by surface decorating them with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and imaging. ICG was chosen as an imaging and hyperthermia agent and DOX was used as a chemotherapeutic agent. ICG and DOX were incorporated into PLGA nanoparticles using the oil-in-water emulsion solvent evaporation technique.

Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating.

Background: In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of near-infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT).

Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation.

Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb).

Near-infrared fluorescing IR820-chitosan conjugate for multifunctional cancer theranostic applications.

This study reports the preparation and characterization of IR820-chitosan conjugates that have potential multifunctional imaging-hyperthermia applications in cancer. The conjugates were formulated by covalentcouplingofchitosan to a carboxyl derivatized IR820, and studied for optical imaging and hyperthermia applications. IR820-chitosan conjugates were able to generate heat upon exposure to 808nm laser and produce hyperthermic cell growth inhibition in cancer cell lines MES-SA, SKOV-3 and Dx5.

[Cloning, expression and purification of human PNAS-4].

Objective: To clone a novel apoptosis-related gene, human PNAS-4, and to get it expressed in E. coli.

Methods: Human PNAS-4 gene was amplified by RT-PCR form A549 human lung adenocarcinoma cells and inserted into pGEX-6P-1 vector.

Real-time monitoring biomarker expression of carcinoma cells by surface plasmon resonance biosensors.

A novel surface plasmon resonance (SPR) biosensor which is capable of monitoring proteomic biomarker secretion from living cells is reported here. Vascular endothelial growth factor (VEGF) secretion from living SKOV-3 ovarian cancer cells was measured for concept demonstration.

Nanoplexes for cell imaging and hyperthermia: in vitro studies.

Novel IR820-polyethylene glycol-diamine nanoplexes (IR820-PDNCs) have potential multifunctional imaging-hyperthermia applications in cancer. Nanoplexes were formulated by ionic interaction and characterized in vitro for their imaging and hyperthermia capabilities. The resulting nanoplexes were approximately 50 nm diameter, with a zeta potential of 2.

Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells.

Protein phosphorylation plays an important role in the regulation of self-renewal and differentiation of embryonic stem cells. However, the responsible intracellular kinases are not well characterized. Here, we discovered that cyclin K protein was highly expressed in pluripotent embryonic stem cells but low in their differentiated derivatives or tissue-specific stem cells.

Comparative study of the optical and heat generation properties of IR820 and indocyanine green.

AbstractNear-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration.

Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer cell lines with different drug resistance mechanisms.

Unlabelled: The purpose of this study was to compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin (DOX)-loaded poly(d,l-lactide co-glycolide) (PLGA) nanoparticle (NP) drug delivery systems in drug-resistant ovarian (SKOV-3) and uterine (MES-SA/Dx5) cancer cell lines. The cellular uptakes of DOX from nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody-conjugated DOX-loaded NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both free DOX and DNPs treatment.

Simultaneous delivery of chemotherapeutic and thermal-optical agents to cancer cells by a polymeric (PLGA) nanocarrier: an in vitro study.

Purpose: To test the effectiveness of a dual-agent-loaded PLGA nanoparticulate drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in a DOX-sensitive cell line and two resistant cell lines that have different resistance mechanisms.

Methods: The DOX-sensitive MES-SA uterine sarcoma cell line was used as a negative control. The two resistant cell lines were uterine sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P-glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to doxorubicin due to a p53 gene mutation.