Copper Nanodrugs with Controlled Morphologies through Aqueous Atom Transfer Radical Polymerization.

Copper (Cu) nanodrugs can be facilely prepared through atom transfer radical polymerization (ATRP) in an aqueous medium. However, it is difficult to control the morphology of Cu nanodrugs and thereby optimize their anticancer activity. In this work, aqueous ATRP was combined with polymerization-induced self-assembly (PISA) to prepare Cu nanodrugs with various morphologies. We mapped the relationship between polymerization condition and product morphology in which each morphology shows a wide preparation window. Decreasing the reaction temperature and feeding more Cu catalysts can improve the mobility of chains, facilitating the morphology evolution from sphere to other high-order morphologies. The resultant Cu nanodrugs with high monomer conversion and high Cu loading efficiency could be easily taken by cancer cells, showing excellent anticancer efficacy in vitro. This work proposed a potential strategy to prepare Cu nanodrugs with a specific morphology in batches, providing the method to optimize the anticancer efficacy through morphology control.

Copper Nanodrugs by Atom Transfer Radical Polymerization.

In this study, some copper catalysts used for atom transfer radical polymerization (ATRP) were explored as efficient anti-tumor agents. The aqueous solution of copper-containing nanoparticles with uniform spheric morphology was in situ prepared through a copper-catalyzed activator generated by electron transfer (AGET) ATRP in water. Nanoparticles were then directly injected into tumor-bearing mice for antitumor chemotherapy. The copper nanodrugs had prolonged blood circulation time and enhanced accumulation at tumor sites, thus showing potent antitumor activity. This work provides a novel strategy for precise and large-scale preparation of copper nanodrugs with high antitumor activity.

Cooperative, reversible self-assembly of covalently pre-linked proteins into giant fibrous structures.

We demonstrate a simple bioconjugate polymer system that undergoes reversible self-assembling into extended fibrous structures, reminiscent of those observed in living systems. It is comprised of green fluorescent protein (GFP) molecules linked into linear oligomeric strands through click step growth polymerization with dialkyne poly(ethylene oxide) (PEO). Confocal microscopy, atomic force microscopy, and dynamic light scattering revealed that such strands form high persistence length fibers, with lengths reaching tens of micrometers, and uniform, sub-100 nm widths. We ascribe this remarkable and robust form of self-assembly to the cooperativity arising from the known tendency of GFP molecules to dimerize through localized hydrophobic patches and from their covalent pre-linking with flexible PEO. Dissipative particle dynamics simulations of a coarse-grained model of the system revealed its tendency to form elongated fibrous aggregates, suggesting the general nature of this mode of self-assembly.

Catalyst- and Solvent-Free Upcycling of Poly(Ethylene Terephthalate) Waste to Biodegradable Plastics.

Poly(ethylene terephthalate) (PET) is an important polymer with annual output second only to polyethylene. Due to its low biodegradability, a large amount of PET is recycled for sustainable development. However, current strategies for PET recycling are limited by low added value or small product scale. It is urgent to make a breakthrough on the principle of PET macromolecular reaction and efficiently prepare products with high added value and wide applications. Here, the catalyst- and solvent-free synthesis of biodegradable plastics are reported through novel carboxyl-ester transesterification between PET waste and bio-based hydrogenated dimer acid (HDA), which can directly substitute some terephthalic acid (TPA) units in PET chain by HDA unit. This macromolecular reaction can be facilely carried out on current equipment in the polyester industry without any additional catalyst and solvent, thus enabling low-cost and large-scale production. Furthermore, the product semi-bio-based copolyester shows excellent mechanical properties, regulable flexibility and good biodegradability, which is expected to substitute poly(butylene adipate-co-terephthalate) (PBAT) plastic as high value-added biodegradable materials. This work provides an environmental-friendly and economic strategy for the large-scale upcycling of PET waste.

Preoperative Serum Lipids as Novel Predictors of Survival in 3575 Papillary Thyroid Cancer Patients.

PURPOSE: The objective of this study is to investigate the association between preoperative serum lipids levels and papillary thyroid cancer (PTC) patients' outcomes. METHODS: A retrospective cohort study including 3575 PTC patients from year 2012-2016 with follow-ups in our institute were enrolled. Preoperative serum lipids were divided into categorical variables by Receiver-operating curves. Univariable and multivariable cox regression models were developed and independent risk factors were used to construct a nomogram to predict disease-free survival (DFS) rate. RESULTS: Among the 3575 patients, the mean follow-up time was 56.7 months. Comparing with the patients with high level of triglycerides (TAG≥0.605 mmol/L) and high-density lipoprotein (HDL≥0.935 mmol/L), those with low level of TAG (hazard ratio [HR] 2.28 [95% CI, 1.35-3.83]) and HDL (HR 1.64, [1.02-2.62]) had a significantly higher risk of recurrence in PTCs. The 5-year DFS rate of patients with low level of TAG was 94.4%, which was much lower than that in the high level group (97.2%, P＜0.001). While TC (P = 0.13), LDL (P = 0.07) and VLDL (P = 0.15) were not statistically correlated with PTCs' recurrence. The nomogram model showed clinical predictive value with the c-index of 0.80 (95% CI 0.73-0.87) and 0.82 (95% CI 0.73-0.90) for 3- and 4-year DFS in the training cohorts. CONCLUSION: In the present study, we provide initial evidence that low levels of TAG and HDL were independently associated with the recurrence of PTC, indicating that preoperative serum concentrations of lipids are helpful in predicting PTC patients' prognosis in clinical practice.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Zinc hybrid polyester barrier membrane accelerates guided tissue regeneration.

Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.

Catalytic Amounts of an Antibacterial Monomer Enable the Upcycling of Poly(Ethylene Terephthalate) Waste.

Poly(ethylene terephthalate) (PET) is an important polymer with an annual output second only to polyethylene. The development of PET recycling technologies is therefore necessary to not only eliminate the harm associated with white pollution and microplastics, but also to reduce carbon emissions. Antibacterial PET, one of the most high-value advanced materials, has improved the ability to treat bacterial infections. However, current methods of manufacturing commercial antibacterial PET require blending with an excess of metal-based antibacterial agents, which leads to biotoxicity and a nonpersistent antibacterial activity. In addition, high-efficiency organic antibacterial agents have yet to be employed in antibacterial PET due to their poor thermal stabilities. Herein, a solid-state reaction for the upcycling of PET waste using a novel hyperthermostable antibacterial monomer is described. This reaction is catalyzed by the residual catalyst present in the PET waste. It is found that a catalytic amount of the antibacterial monomer enabled the low-cost upcycling of PET waste to produce high-value recycled PET with a strong and persistent antibacterial activity, as well as similar thermal properties to the virgin PET. This work provides a feasible and economic strategy for the large-scale upcycling of PET waste and exhibits potential for application in the polymer industry.

Construction of an antibacterial low-defect hybrid layer by facile PEI electrostatic assembly promotes dentin bonding.

Dentin bonding is the most common form of human tissue repair among tissue-biomaterial adhesions, concerning billions of people's oral health worldwide. However, insufficient adhesive infiltration in the demineralized dentin matrix (DDM) always produces numerous defects in the bonding interface termed the hybrid layer, which causes high levels of bacteria-related secondary dental diseases, and less than 50% of the bonding lasts more than 5 years. Therefore, it is urgent and vital to construct an antibacterial low-defect hybrid layer to solve the durability-related problems. A DDM with a hydrogel-like surface formed by the hydration of highly-anionic non-collagenous proteins (NCPs) is firstly used as a template to electrostatically assemble polyethyleneimine (PEI). The formation of a stable antibacterial polyelectrolyte complex of PEI/NCPs rapidly eliminates NCP hydration capacity and significantly improves the infiltration of various adhesives. Simultaneously, both the PEI during the assembly and the PEI-assembled DDM can directly destroy a biofilm of S. Mutans on the DDM. Consequently, a long-term antibacterial and low-defect hybrid layer is successfully created, which greatly improves the bonding effectiveness. This helps to improve the clinical treatment of bacteria-based dental diseases and the tooth-restoration repair effect and prevent secondary dental diseases, having significance in clinical dentistry and providing insights for other tissue-biomaterial adhesions.

Click-based injectable bioactive PEG-hydrogels guide rapid craniomaxillofacial bone regeneration by the spatiotemporal delivery of rhBMP-2.

Craniomaxillofacial bone defects result in physical and psychological dual injuries making the promotion or acceleration of bone regeneration imperative. In this work, a fully biodegradable hydrogel is facilely prepared via thiol-ene "click" reactions under human physiological conditions using multifunctional poly(ethylene glycol) (PEG) derivatives as precursors. This hydrogel shows excellent biological compatibility, enough mechanical strength, a low swelling rate and an appropriate degradation rate. Rat bone marrow mesenchymal stem cells (rBMSCs) can survive and proliferate on/in the PEG hydrogel and differentiate into osteogenic cells. The PEG hydrogel can also effectively load rhBMP-2 through the above "click" reaction. Under the physical barrier of the chemically crosslinked hydrogel network, the spatiotemporal release of rhBMP-2 effectively promotes the proliferation and osteogenic differentiation of rBMSCs at a loading concentration of 1 µg ml-1. Finally, based on a rat calvarial critical-size defect model, the rhBMP-2 immobilized hydrogel loaded with rBMSCs basically accomplishes the repair and regeneration within 4 weeks featured by remarkably enhanced osteogenesis and angiogenesis. The click-based injectable bioactive PEG hydrogel developed in the present study is a new type of bone substitute with great expectations in future clinical applications.