Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP-ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal cancer HCT116 cells and established an acquired PDD00017273-resistant HCT116RPDD cell line. In this study, we analyzed the protein levels of enzymes associated with PAR metabolism in both parental HCT116 cells and resistant HCT116RPDD cells using western blotting. PARG expression levels were similar between HCT116RPDD and HCT116 cells. However, the levels of PARP1 and ARH3 were reduced in HCT116RPDD cells compared to HCT116 cells. Nevertheless, intracellular PAR levels were elevated in HCT116RPDD cells. Interestingly, HCT116RPDD cells exhibited greater sensitivity to γ-ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5-FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116RPDD cells tended to maintain slightly higher levels of intracellular NAD+/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD+ and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP-PARG regulation.

Fossil‐based material manufacturing has long been linked to the acceleration of climate change through carbon dioxide emissions. In addition to their negative impact on the environment, the depletion of nonrenewable fossil fuels has led to a global demand for sustainable and environmentally friendly alternatives. This has sparked a surge of academic interest in the past few decades on the manufacture of bio‐based materials as substitutes for fossil‐based materials. As sustainability becomes a global imperative, bioplastics are rapidly emerging as a viable alternative to conventional petroleum‐derived plastics. These materials might be manufactured by using polymers from different bio‐based sources such as plants, animal tissues, or can have a microbial origin. Bioplastics not only offer biodegradability, thereby reducing long‐term environmental impact, but also possess various functional properties that make them suitable for diverse applications, including packaging, agriculture, textiles and pharmaceuticals. This review focuses on new developments in bioplastics regarding their material, processing, and applications. Recent developments in the preparation of bioplastics are reported, highlighting the distinct properties of each type of material according to the polymers of origin. Special attention is given to the film‐forming properties, the barrier functionality, thermal stability, and compatibility with the bioactive compounds, supported by recent empirical findings.

The DUF4465 family (DUF, domain of unknown function) contains more than 1000 members distributed across eight bacterial clades with species from diverse microenvironments including various gut microbiomes, hydrothermal vents, and soil. In the gut commensal Bacteroides thetaiotaomicron (B. theta), DUF4465 containing proteins act as high-affinity B12-binding proteins that scavenge this cofactor to ensure bacterial survival. Such B12 capture is essential for bacteria that have lost the ability to synthesize B12 de novo. This raises the question of whether B12-binding is ubiquitous across this family of proteins. Here, we show that B12-binding is a recurrent function of eight distantly related members of the DUF4465 family. It is reasonable to conclude that B12-binding is a common function of most DUF4465 proteins. These results establish DUF4465 as a structurally conserved family of augmented β-jellyroll B12-binding proteins with widespread roles in microbial competition for this essential cofactor. Impact statement DUF4465 defines a widespread, structurally conserved bacterial cobalamin-binding domain and provides a promising scaffold for protein-based B12 capture and purification.

Breast carcinoma (BC) is the most common malignancy in women, with triple-negative breast cancer (TNBC) making up 10-20% of cases. TNBC has limited targeted therapies and poor survival due to late diagnosis and metastasis. Dendrimers are precise nanostructures with a three-dimensional globular architecture designed to target the negatively charged membranes of cancer cells. This study evaluated the anticancer potential of two novel core-shell polycationic polyurea (PURE) dendrimers, PUREG4-OEI48 and PUREG4-OCEI24, targeting BC cell membranes. Both dendrimers selectively interacted with TNBC cells, inducing apoptosis, necroptosis, and ferroptosis. In vivo, they reduced tumor volume in HCC1806 xenografts, with PUREG4-OEI48 showing no toxicity, while PUREG4-OCEI24 induced mild hepatic toxicity. These results suggest PURE dendrimers are promising TNBC treatments, with further modifications needed to enhance efficacy and reduce toxicity.

Erythropoiesis is a highly coordinated process that generates mature red blood cells from hematopoietic stem-progenitor cells (HSPCs). Erythropoietin (EPO) is a major regulator of erythropoiesis and binds to the erythropoietin receptor (EPOR), leading to increased erythroid differentiation and proliferation. MicroRNAs (miRs) are important developmental regulators, and distinct miR expression patterns are associated with specific stages of hematopoietic differentiation. Expression profiling of EPO-stimulated human HSPCs revealed increased expression of miR-513a-5p in early erythroid cells. Enforced expression of miR-513a in primary human CD34+ HSPCs promoted erythroid differentiation, as determined by cell-surface marker expression and increased levels of erythroid molecules including hemoglobin. Similar results were observed in human TF-1 erythroleukemia cells, where miR-513a stimulated erythroid differentiation including increased GATA1 and hemoglobin expression and decreased GATA2 expression, even in the absence of EPO. Notably, miR-513a promoted erythroid differentiation in EPOR knockout (KO) TF-1 cells, but not in GATA1 KO TF-1 cells, indicating that miR-513a requires GATA1, but not EPOR, to stimulate erythropoiesis. Further analysis revealed that enforced expression of miR-513a was associated with reduced c-Jun and phospho-c-Jun protein levels. Overexpression of c-Jun inhibited both EPO- and miR-513a-stimulated erythropoiesis. Conversely, c-Jun KO TF-1 cells had increased hemoglobin protein expression, even in the absence of EPO, phenocopying miR-513a overexpression. In summary, this study identifies miR-513a as a positive regulator of early human erythropoiesis and supports a role for miR-513a in promoting erythroid differentiation by modulating c-Jun expression and increasing GATA1 expression.

NID2 is a key component of the BM and plays an important role in ECM organization and tumor-associated microenvironmental remodeling. In this study, full-length recombinant NID2 was used as an antigen to immunize camels, and a nanobody phage display library was constructed from peripheral blood lymphocytes. Using phage display-based screening, nanobodies recognizing distinct epitopes within the NID2 G1G2 and rod-G3 domains were isolated and characterized. Epitope specificity and competition were further analyzed by BLI, allowing the identification of nonoverlapping nanobody pairs. Based on these results, two high-affinity nanobodies were selected to establish a nanobody-based sandwich ELISA for NID2 detection. This assay enabled the detection of recombinant NID2 at concentrations down to 10 ng·mL-1 in human serum. Although the analytical sensitivity is lower than that of some commercial antibody-based ELISA kits, the nanobody-based format offers advantages in terms of recombinant production, scalability, and assay design flexibility. Collectively, this study provides a panel of domain-selective nanobodies against NID2 and establishes a nanobody-based sandwich ELISA as a methodological platform for future investigations of serum NID2 in diagnostic and translational research contexts.