Serum glycosylated hemoglobin and prostate cancer risk: Results from a systematic review and dose-response meta-analysis.

OBJECTIVES: To evaluate the correlation between serum glycosylated hemoglobin (HbA1c) levels and the risk of prostate cancer incidence and mortality, providing a comprehensive analysis to inform preventative and clinical strategies. METHODS: A systematic review and meta-analysis was conducted including studies based on their documentation of prostate cancer incidence and mortality related to HbA1c levels, with a minimum of 3 risk-related data levels. The Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for quality assessment and risk of bias evaluation. We employed generalized least squares (GLS) to assess the linear trend within individual studies and combined these estimates using a random effects model. Additionally, we utilized a restricted cubic spline (RCS) model to investigate potential nonlinear trends. RESULTS: A total of 13 studies were included in the quantitative synthesis ultimately. The quantitative analysis did not find a significant association between HbA1c levels and prostate cancer incidence. However, a significant positive correlation was revealed between HbA1c levels and both cancer-specific mortality (CSM) and all-cause mortality (ACM), with a 1% increase in HbA1c levels associated with a 26% increase in CSM and a 21% increase in ACM. CONCLUSION: The HbA1c level is significantly associated with increased prostate cancer mortality. The results highlight the importance of considering blood sugar control in the comprehensive risk assessment for prostate cancer, particularly among the nondiabetic population.

Design, synthesis and optimization of pyrazolo[3,4-b] pyridine derivatives as Hsp110-STAT3 interaction disruptors for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal cardiovascular disorder that is characterized by pulmonary vascular remodeling. Our previous results demonstrated that heat shock protein (Hsp110) was significantly activated to induce vascular remodeling by enhancing the Hsp110-STAT3 interaction. The development of inhibitors that disrupt this association represents a novel strategy for the treatment of PAH. This study is committed to finding new inhibitors targeting the Hsp110-STAT3 interaction based on the structure of the lead compound 2h. A fusion design principle was employed in conjunction with structural optimization in the identification of the compound 10b. In vitro data indicates that 10b exhibited greater potency in the inhibition of pulmonary vascular cells malignant phenotypes via impeding the chaperone function of Hsp110 and the Hsp110-STAT3 interaction. In hypoxia-induced PAH rats, administration of 10b significantly attenuated vascular remodeling and right ventricular hypertrophy by inhibiting the Hsp110-STAT3 association. In short, this work identified a novel and promising lead compound for the development of anti-PAH drugs targeting the Hsp110-STAT3 interaction.

SUMO: A new perspective to decipher fibrosis.

Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin-like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO-mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear-cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO-specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF-κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis-related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases.

Allosteric site identification, virtual screening and discovery of a sulfonamide Hsp110-STAT3 interaction inhibitor for the treatment of hypoxic pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disorder marked by vascular remodeling, which is linked to the malignant phenotypes of pulmonary vascular cells. The prevailing therapeutic approaches for PAH tend to neglect the potential role of vascular remodeling, leading to the clinical prognosis remains poor. Previously, we first demonstrated that heat shock protein (Hsp110) was significantly activated to boost Hsp110-STAT3 interaction, which resulted in abnormal proliferation and migration of human pulmonary arterial endothelial cells (HPAECs) under hypoxia. In the present study, we initially postulated the allosteric site of Hsp110, performed a virtual screening and biological evaluation studies to discover novel Hsp110-STAT3 interaction inhibitors. Here, we identified compound 29 (AN-329/43448068) as the effective inhibitor of HPAECs proliferation and the Hsp110-STAT3 association with good druggability. In vitro, 29 significantly impeded the chaperone function of Hsp110 and the malignant phenotypes of HPAECs. In vivo, 29 remarkably attenuated pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-induced PAH rats (i.g). Altogether, our data support the conclusion that it not only provides a novel lead compound but also presents a promising approach for subsequent inhibitor development targeting Hsp110-STAT3 interaction.

ß-arrestin2: an emerging player and potential therapeutic target in inflammatory immune diseases.

ß-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that ß-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-ß pathways of non-GPCRs. Earlier studies have identified that ß-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, ß-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of ß-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of ß-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases.

Synthesis of Antifouling Poly(ethylene glycol) Brushes via "Grafting to" Approach for Improved Biodistribution.

Polyethylene glycol (PEG) modification of materials has been identified to mitigate the challenge of biofouling. However, the practical application of PEGylation has been hampered by a low PEGylation density on the material surface. Therefore, developing efficient strategies to promote the PEGylation density is crucial. In this study, PEG brushes (PBs) with various structures were synthesized and their physicochemical properties and biomedical applications were investigated. Compared to benzaldehyde (BA), o-phthalaldehyde (OPA) exhibited higher reactivity with amine groups, resulting in increased grafting density (as high as 96.3%) and improved antifouling properties of PEG brushes. Bottlebrushes fabricated by PEG-OPA and polylysine demonstrated a prolonged circulation time in blood and enhanced potential for magnetic resonance imaging of tumors. Furthermore, the rigidity of the backbone was found to be crucial for the antifouling properties of PEG brushes both in vitro and in vivo. These findings are significant and provide valuable insights into designing biomaterials with superior antifouling performance.

Metal-Phenolic Vehicles Potentiate Cycle-Cascade Activation of Pyroptosis and cGAS-STING Pathway for Tumor Immunotherapy.

The treatment of triple-negative breast cancer (TNBC) faces challenges due to its limited immune response and weak tumor immunogenicity. A collaborative strategy involves combining the activation of pyroptosis and the stimulator of interferon genes (STING) pathway to enhance tumor immunogenicity and fortify the antitumor immune response, which may improve therapeutic outcomes in TNBC. In this study, we report the fabrication of a zinc-phenolic nanocapsule (RMP@Cap), which is loaded with mitoxantrone (MTO) and anti-PD-L1 antibodies (aPD-L1) and coated with erythrocyte membrane, for TNBC immunotherapy. The delivery of RMP@Cap can induce tumor cell pyroptosis and, therefore, trigger the release of mitochondrial DNA, which further combines with zinc agonists to intensify STING activation, resulting in a cascade amplification of the therapeutic effect on tumors. Additionally, the incorporation of aPD-L1 into the zinc-phenolic nanocapsule relieves the inhibitory effect of tumor cells on recruited cytotoxic T cells, thereby improving the tumor-killing capacity. Furthermore, the incorporation of a camouflaged erythrocyte membrane coating enables nanocapsules to achieve prolonged in vivo circulation, resulting in improved tumor accumulation for effective antitumor therapy. This study demonstrates a synergistic therapeutic modality involving pyroptosis, coupled with the simultaneous activation and cyclic amplification of the STING pathway in immunotherapy.

Prioritising Key Concepts for informed health choices in cancer: An evidence-based online educational programme.

Objective: The overabundance of health misinformation has undermined people's capacity to make evidence-based, informed choices about their health. Using the Informed Health Choices (IHC) Key Concepts (KCs), we are developing a two-stage education programme, Informed Health Choices-Cancer (IHC-C), to provide those impacted by cancer with the knowledge and skills necessary to think critically about the reliability of health information and claims and make well-informed choices. Stage 1 seeks to prioritise the most relevant Key Concepts. Methods: A project group and a patient and carer participation group completed a two-round prioritisation process. The process involved disseminating pre-reading materials, training sessions, and a structured judgement form to evaluate concepts for inclusion. Data from each round were analysed to reach a consensus on the concepts to include. Results: Fourteen participants were recruited and completed the first-round prioritisation. Fifteen participants undertook the second-round prioritisation. Nine Key Concepts were selected for the programme across five training sessions and two consensus meetings. Conclusion: The prioritised concepts identified represent the most pertinent aspects of cancer-related information for those impacted by the disease. By incorporating these concepts into educational materials and communication strategies, healthcare providers and organisations can potentially help cancer patients, survivors, and their loved ones to recognise and combat cancer-related misinformation more effectively. Innovation: This study introduces a participatory prioritisation process, which integrates the expertise of healthcare professionals with the insights of patients and carers, thereby enhancing the programme's relevance and applicability.

Red Blood Cell-Like Poly(ethylene glycol) Particles: Influence of Particle Stiffness on Biological Behaviors.

Cell-like particles represent a category of synthetic particles designed to emulate the structures or functions of natural cells. Herein, we present the assembly of cell-like poly(ethylene glycol) (PEG) particles with different stiffnesses and shapes via replication of animal cells and investigate the impact of particle stiffness on their biological behaviors. As a proof of concept, we fabricate red blood cell-like and spherical PEG particles with varying cross-linking densities. A systematic exploration of their properties, encompassing morphology, stiffness, deformability, and biodistribution, reveal the vital influence of particle stiffness on in vivo fate, elucidating its role in governing the traversal of capillaries and the dynamic interactions with phagocytic cells.

Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense.

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca2+. Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer.Abbreviations: AMPK: AMP-activated protein kinase; BAF1: bafilomycin A1; ConA: concanamycin A; DOX: doxycycline; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; LN: low nutrient; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NSCLC: non-small cell lung cancer; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PPP2/PP2A: protein phosphatase 2; ROS: reactive oxygen species; PPP3/calcineurin: protein phosphatase 3; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TCL: total cell lysate; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; V-ATPase: vacuolar-type H+-translocating ATPase.

Bioaccumulation of Arsenic, Cadmium, Chromium, Cobalt, Copper, and Zinc in Uroteuthis edulis from the East China Sea.

In this study, the concentrations of trace elements (TEs) in Uroteuthis edulis caught from the East China Sea were determined. There were significant differences between TE concentrations in different body parts. Cu, Zn, and Cd were the most concentrated in the digestive glands and the concentrations of Cr and Co were highest in the gills. No significant differences in concentrations were shown between these tissues. In the four tissues analyzed, the mantle recorded the highest proportion of elemental load, while the digestive glands and gills had the lowest proportions. After maturity, TEs in the mantle showed no significant differences. In the digestive gland, the concentrations of all elements, except Zn, were significantly increased. The gonads illustrated apparent increases in the concentrations of Cr, Cu, and As. In the gills, the concentrations of Co and As were markedly increased.

Discovery and Optimization of Hsp110 and sGC Dual-Target Regulators for the Treatment of Pulmonary Arterial Hypertension.

Currently, bifunctional agents with vasodilation and ameliorated vascular remodeling effects provide more advantages for the treatment of pulmonary arterial hypertension (PAH). In this study, we first screened the hit 1 with heat shock protein 110 (Hsp110) inhibition effect from our in-house compound library with soluble guanylate cyclase (sGC) activity. Subsequently, a series of novel bisamide derivatives were designed and synthesized as Hsp110/sGC dual-target regulators based on hit 1. Among them, 17i exhibited optimal Hsp110 and sGC molecular activities as well as remarkable cell malignant phenotypes inhibitory and vasodilatory effects in vitro. Moreover, compared to riociguat, 17i showed superior efficacy in attenuating pulmonary vascular remodeling and right ventricular hypertrophy via Hsp110 suppression in hypoxia-induced PAH rat models (i.g.). Notably, our study successfully demonstrated that the simultaneous regulation of Hsp110 and sGC dual targets was a novel and feasible strategy for PAH therapy, providing a promising lead compound for anti-PAH drug discovery.

TRIM26 deficiency enhancing liver regeneration through macrophage polarization and ß-catenin pathway activation.

Liver regeneration is a complex process involving the crosstalk between parenchymal and non-parenchymal cells, especially macrophages. However, the underlying mechanisms remain incompletely understood. Here, we identify the E3 ubiquitin ligase TRIM26 as a crucial regulator of liver regeneration. Following partial hepatectomy or acute liver injury induced by carbon tetrachloride, Trim26 knockout mice exhibit enhanced hepatocyte proliferation compared to wild-type controls, while adeno-associated virus (AAV)-mediated overexpression of Trim26 reverses the promotional effects. Mechanistically, Trim26 deficiency promotes the recruitment of macrophages to the liver and their polarization towards pro-inflammatory M1 phenotype. These M1 macrophages secrete Wnts, including Wnt2, which subsequently stimulate hepatocyte proliferation through the activation of Wnt/ß-catenin signaling. In hepatocytes, Trim26 knockdown reduces the ubiquitination and degradation of ß-catenin, thereby further enhancing Wnt/ß-catenin signaling. Pharmacological inhibition of Wnt/ß-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/ß-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings.

The health benefits of dietary polyphenols on pediatric intestinal diseases: Mechanism of action, clinical evidence and future research progress.

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

Induction of CX3CL1 expression by LPS and its impact on invasion and migration in oral squamous cell carcinoma.

Purpose: This study aimed to explore the expression of CX3CL1 induced by lipopolysaccharide (LPS) in oral squamous cell carcinoma (OSCC) and its impact on biological characteristics such as invasion and migration, taking the foundation for new targets for the treatment and prognosis of OSCC. Methods: This study utilized a variety of techniques, including bioinformatics, molecular biology, and cell experiments, to investigate the expression of CX3CL1 and its receptor CX3CR1 in OSCC patients' cancer tissues or OSCC cell lines. Extracting, organizing, and analyzing the TCGA database on the expression of CX3CL1 and its receptor CX3CR1 in cancer tissues and corresponding paracancerous normal tissues of OSCC patients by bioinformatics methods. The expression of CX3CL1 in cancerous and normal tissues of OSCC patients was verified by IHC, and the changes in mRNA and protein expression of CX3CL1 and its receptor CX3CR1 in OSCC cell lines were detected before and after lipopolysaccharide LPS stimulation by RT-PCR, ELISA, and WB. Changes in cell biological behavior by overexpression of CX3CL1 in OSCC cell lines were detected by CCK-8, Transwell, scratch healing assay, and cloning assay. The effects of overexpressing cell lines on the AKT pathway and Epithelial-mesenchymal Transition (EMT)-related protein expression before and after LPS stimulation were detected by Western Blot. Results: (1) CX3CL1 and its receptor CX3CR1 were found to be downregulated in OSCC tissues of patients or OSCC cell lines. (2) After LPS stimulation, CX3CL1 gene expression increased in both OSCC cell lines, while CX3CR1 expression remained unchanged. (3) OSCC cell lines overexpressing CX3CL1 showed changes in cell biological characteristics, including decreased proliferation, invasion, migration, and stemness, which were more pronounced after LPS stimulation. (4) Overexpression of CX3CL1 in OSCC cell lines decreased EMT-related protein expression and AKT phosphorylation. On the contrary were promoted by LPS stimulation. Conclusion: CX3CL1 and CX3CR1 are downregulated in OSCC cancer tissues and cell lines compared to adjacent normal tissues and cells. LPS stimulation increases CX3CL1 expression in OSCC cell lines, suggesting that inflammation may induce CX3CL1 expression and that the CX3CL1 gene may play an important role in OSCC progression. Overexpression of CX3CL1 inhibits OSCC cell proliferation, migration, invasion, and stemness, suggesting that CX3CL1 plays a critical role in suppressing OSCC development. CX3CL1 suppresses OSCC invasion and migration by affecting EMT progression and AKT phosphorylation, and partially reverse the process that LPS causes and affects the development of OSCC.

Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study.

BACKGROUND: The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. METHODS: This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. RESULTS: The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. CONCLUSION: HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.

Metal-Phenolic Network-Coated Nanoparticles as Stabilizers for the Engineering of Pickering Emulsions with Bioactivity.

Pickering emulsions stabilized by functional nanoparticles (NPs) have received considerable attention for improving the physical stability and biological function of NPs. Herein, hydrophobic polyphenols were chosen as phenolic ligands to form metal-phenolic network (MPN) coatings on NPs (e.g., silica, polystyrene) mediated by the sono-Fenton reaction. The MPN coatings modulated the surface wettability and charges of NPs and achieved emulsification behavior for preparing Pickering emulsions with pH responsiveness and oxidation resistance. A series of polyphenols, including resveratrol, rutin, naringin, and curcumin, were used to form MPN coatings on NPs, which served as stabilizers for the engineering of functionalized oil-in-water (O/W) Pickering emulsions. This work provides a new avenue for the use of hydrophobic polyphenols to modulate NP emulsifiers, which broadens the application of polyphenols for constructing Pickering emulsions with antioxidant properties.

Tetracalcium phosphate/porous iron synergistically improved the mechanical, degradation and biological properties of polylactic acid scaffolds.

Synergistically improving the mechanical and degradable properties of polylactic acid (PLA) scaffolds and endowing them with bioactivity are urgent problems to be solved in deepening their application in tissue engineering. In this work, tetracalcium phosphate (TTCP) and porous iron (pFe) were compounded by stirring and vacuum negative pressure, and then they were blended with polylactic acid and a porous scaffold (named TTCP@pFe/PLA) was prepared by selective laser sintering. On the one hand, molten polylactic acid penetrates the pores of porous iron to form an interlocking network, thereby achieving mechanical strengthening. On the other hand, the alkaline environment generated by the dissolution of tetracalcium phosphate can effectively catalyze the hydrolysis of polylactic acid to accelerate the degradation. Meanwhile, the dissolution of tetracalcium phosphate forms a local calcium-rich microenvironment, which rapidly induces apatite formation, that is, confers bioactivity on scaffolds. As a result, the TTCP@pFe/PLA scaffold exhibited a notable enhancement in mechanical strength, being 2.2 times stronger compared to the polylactic acid scaffold. More importantly, MC3T3E1 cells exhibit good adhesion, stretching, and proliferation on the composite scaffold, demonstrating good cytocompatibility. All these good properties of the TTCP@pFe/PLA scaffold indicate that it has potential applications as a novel alternative in bone tissue regeneration.