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We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure-activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, i.e. , we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog  P . Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.

Cerebral ischemic stroke, neuronal death, and inflammation bring difficulties in neuroprotection and rehabilitation. In this study, we developed and designed the ability of natural lactoferrin-polyethylene glycol-polyphenylalanine-baicalein nanomicelles (LF-PEG-PPhe-Bai) to target and reduce these pathological processes, such as neurological damage and cognitive impairment in the stages of poststroke. Nanomicelles made from biocompatible materials have improved bioavailability and targeted distribution to afflicted brain areas. The results showed that LF-PEG-PPhe-Bai greatly improved the antioxidation, antiapoptosis, and anti-inflammation activity in vitro . Meanwhile, LF-PEG-PPhe-Bai improved the behavioral and cognitive impairment of 2-VO model mice, protected nerve cells in the hippocampus, and reduced inflammation at the brain injury site in vivo . In conclusion, LF-PEG-PPhe-Bai nanomicelles are employed for enhancing neuroprotection and poststroke rehabilitation. The development of this technology might provide a new technique for neural repair after ischemia in the future.

Spontaneous intracerebral hemorrhagic stroke (ICH) is a highly aggressive disease, with a high incidence and mortality rate. Iron deposition following ICH leads to oxidative damage and motor dysfunction, significantly impacting the overall quality of life for those affected. Here, a polyphenolic nanomedicine, catechin-based polyphenol nanoparticles surface-modified by thiol-terminated poly(ethylene glycol) (CNPs@PEG), was developed through the oxidative polymerization and self-assembly of catechin, a natural compound in tea. Due to its potent antioxidant and metal-chelating properties, CNPs@PEG effectively maintained blood-brain barrier integrity, reduced brain edema, significantly increased the survival rate of mice with cerebral hemorrhage and markedly improved neurological deficits after ICH. Mechanistically, CNPs@PEG accomplishes this by chelating iron, enhancing tissue antioxidant capacity, reducing oxidative stress, and inhibiting iron deposition. This approach holds promise as a targeted therapeutic strategy for addressing cerebral hemorrhage and other conditions associated with iron overload.

Osmotic shock is the first step of high salt or drought action that involves biochemical and molecular changes during plant response to these unfavorable conditions. Indole-3-acetyl-aspartate (IAA-aspartate, IAA-Asp) is the main amide conjugate of auxin in pea (Pisum sativum L.) tissues. Although the exact molecular mechanism of the IAA-Asp action is unknown, this conjugate's indole-3-acetic acid (IAA)-independent biological activity has been observed during physiological and stress conditions. In this work, we investigated the effect of IAA-Asp alone, as well as in combination with NaCl or polyethylene glycol (PEG) (osmotic shock) on reduced/oxidized glutathione (GSH/GSSG) ratio, activities of enzymes modulating glutathione concentration, protein S-glutathionylation, and IAA homeostasis. We did not observe the hydrolysis of IAA-Asp to IAA in pea seedlings, which, together with other results, suggests that IAA-Asp modulates plant response to abiotic stimuli independently of IAA. Moreover, despite the effect of IAA-Asp on the enzymes responsible for IAA conjugation, no changes in this phytohormone level were visible. Furthermore, 3h plant treatment with IAA-Asp increased the activity of glutathione reductase (GR), which correlates with an elevated GSH/GSSG ratio. On the contrary, more extended (48h) incubation with IAA-Asp diminished the GSH/GSSG ratio and increased the activity of glutathione peroxidase (GPX). IAA-Asp reduced GR activity during salt treatment but did not affect the GSH/GSSG ratio. Similarly, under plant incubation with PEG, IAA-Asp did not change the GSH/GSSG ratio but increased glutathione S-transferase (GST) activity. We also analyzed the effect of IAA-Asp on pea protein S-glutathionylation. Increased S-glutathionylation of heat shock 70 kDa protein (HSP70) was observed after plant treatment with IAA-Asp, PEG, or IAA-Asp combined with PEG. The proteomic analysis also revealed that IAA-Asp diminished S-glutathionylation of lipoxygenase during plant incubation with PEG. Thus, we suggest that IAA-Asp modulates redox status in pea during oxidative stress and under normal physiological conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

BBT-059 is a long-acting PEGylated interleukin-11 analog that has been shown to have hematopoiesis-promoting and anti-apoptotic attributes, and is being studied as a radiation countermeasure for the hematopoietic acute radiation syndrome (H-ARS). This potential countermeasure has been demonstrated to enhance survival in irradiated mice. To investigate the toxicity and safety profile of this agent, 14 nonhuman primates (NHPs, rhesus macaques) were administered two different doses of BBT-059 subcutaneously 24 h after 4 Gy total-body irradiation and were monitored for the next 60 days postirradiation. Blood samples were investigated for the pharmacokinetics and pharmacodynamics of this agent and its effects on complete blood counts, cytokines, vital signs, and metabolomics. No adverse health effects were observed in either treatment group. Radiation-induced metabolomic dysregulation was observed in both treatment groups, and BBT-059 afforded some short-term radiomitigation. A few pathways were commonly dysregulated by radiation exposure including steroid hormone biosynthesis pathways, fatty acid activation, and glycerophospholipid metabolism. Notably, radiation-induced dysregulation to the linoleate metabolism pathway was significantly mitigated by either dose of BBT-059. In brief, this study suggests that BBT-059 has a good safety profile in irradiated NHPs and that its development as a medical countermeasure for U.S. Food and Drug Administration approval for human use should be continued., (© 2025 by Radiation Research Society. All rights of reproduction in any form reserved.)

The activity of matrix metalloproteinases (MMPs) plays a crucial role in the aging of the resin-dentin interface. The in situ action of MMP-2 and MMP-9 has been confirmed in the process of dentin-collagen degradation. However, the involvement of dental pulp cells in MMP secretion as a response to oxidative stress induced by contact with resin monomers has not been fully elucidated. Myricetin (MYR), like proanthocyanidin (PAC), has antioxidant properties and may help prevent extracellular matrix degradation. The objective was to evaluate the effect of MYR on the MMP expression and activity in response to reactive oxygen species (ROS) increase induced by triethylene glycol dimethacrylate (TEGDMA) in human odontoblast-like cells (hOLCs). hOLCs differentiated from dental pulp mesenchymal stem cells were exposed to TEGDMA released from dentin blocks using a barrier model with transwell inserts for 18, 24, and 36 h. Intracellular oxidation was evaluated using the 2',7'-dichlorofluorescein probe. The effect of 600 μM MYR on the MMP-2 and MMP-9 expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The extracellular MMP levels were quantified using enzyme-linked immunosorbent assay, and their activation by means of a proteolytic fluorometric assay. The results were analyzed by one-way analysis of variance and Tukey's post hoc test, p ≤ 0.05. TEGDMA exposure increased intracellular ROS and upregulated MMP-2 and MMP-9 mRNA in hOLCs (p < 0.001). The levels of MMPs increased significantly 24 h after TEGDMA exposure (p = 0.013). These secreted proteases exhibited high activation ability. MYR reduced ROS production and downregulated MMP expression and activity at both mRNA and protein levels, similar to the effect found for PAC, which was used as a control. A relationship was observed between MMP-2 and MMP-9 expression, secretion, and early activation with ROS increase due to TEGDMA exposure. MYR showed potential as a therapeutic strategy to control MMP expression and modulate redox imbalance, offering a protective effect on cellular response., (© 2025 Wiley Periodicals LLC.)

Autologous hematopoietic stem cell transplantation is used to restore bone marrow function after high-dose chemotherapy. For apheresis, granulocyte colony-stimulating factor (G-CSF) is standard of care, but obtaining sufficient stem cells can be challenging. Other mobilization agents include plerixafor and PEGylated G-CSF (PEG-G-CSF). While efficacy of these is established in adults, limited data for their use in pediatric patients are available. Here, we compare Good versus Poor Mobilizers and study success of different mobilization regimens in regard to CD34 + cell-collection, -quality, -phenotype and hematologic reconstitution in pediatric patients. In this multi-center retrospective study, we analyzed data of 278 patients with solid tumors and lymphoma, mobilized with either G-CSF ( n = 224), PEG-G-CSF ( n = 34), or G-CSF/PEG-G-CSF with additional plerixafor ( n = 20). In Poor Mobilizers (13.7% of all patients), addition of plerixafor to G-CSF augmented CD34 + cell collection, without adverse effects on hematologic reconstitution and CD34 + cell quality. PEG-G-CSF-aided mobilization was successful as first-line treatment in two-thirds of patients and did not impair hematological reconstitution, compared to G-CSF-only. Within the Poor Mobilizer group, G-CSF+plerixafor increased primitive (CD45RA - CD38 - CD90 + CD49f + ) and CXCR4-expressing CD34 + cells in apheresis products compared to G-CSF-only, without exceeding levels of Good Mobilizers. No plerixafor-related increase in tumor cells was observed in apheresis products. In conclusion, our comprehensive study supports the use of plerixafor and furthermore demonstrates the potential of patient-friendly PEG-G-CSF for mobilization of pediatric patients.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Autologous tumor cell membrane antigen-based vaccines (TMVs) have garnered extensive attention as personalized immunotherapy. However, patients who take TMVs therapy usually undergo various treatments prior to surgery, and these processes modulate the immunogenicity of the tumor membrane and the tumor immune microenvironment. Herein, we investigate the impact of preoperative chemotherapy on the efficacy of TMVs. Liposomal doxorubicin ameliorates the immunosuppressive tumor microenvironment and enhances immunological molecule expression on the tumor membrane. This has driven TMVs to elicit a more robust immune response than doxorubicin, resulting in more effective immune protection. The TMVs formulated from liposomal doxorubicin-treated tumors induce superior dendritic cell maturation and T cell activation compared to doxorubicin, thus demonstrating better efficacy in preventing recurrence and metastasis in the postoperative murine model. Collectively, our study suggests that chemotherapy can induce immunomodulatory changes that augment the therapeutic potential of immunotherapy and provides valuable insights into the clinical utilization of TMVs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair., Methods: CeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol-gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI., Results: The Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation., Conclusion: The Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Animal Care and Use Committee of Fudan University (No. 202409029S). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The severe climate change has caused a drastic water level disparity around the globe, which eventually has been one of the biggest problems of this era related to land degradation. This has caused the multidimensional impact on ecology, the environment, and their components. Algae, one of the ancient micro-engineers, are involved in the functioning of soil microcosm. Therefore, this study has utilized a novel alga, Chlorella vulgaris SSAU8 to observe the impact of low water potential induced by PEG-6000 (polyethylene glycol). The study has utilized the UV-Vis spectrophotometer to explore the nature of cyanobacteria by examining biomass and pigment concentrations. The assessment also includes the photosystem response, which was recorded by the Dual-modulation kinetic fluorometer FL3500/F (PSI, Brno, Czech Republic, version 3.7.0.1). The effect of PEG-6000-induced drought was seen to inhibit growth and biomass synthesis at > 30 g L -1 concentration. It was also observed that the microbe could easily shuffle its photosystem behavior to nullify the effect of high PEG-6000 concentration, which shows the potential of the microbe in the water-deficient area and can be an important aspect to enhance soil fertility. Non-photochemical quenching and heat dissipation play a crucial role in cyanobacteria tolerating drought conditions. So, overall, this study thoroughly explores the behavior of Chlorella vulgaris SSAU8 in artificial drought stress and paves a way to combat one of the major environmental issues of the current era., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. All authors also declare that they haven’t used any animal or human subject in the study. Ethical Approval: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer., Methods: Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval., Results: Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed., Conclusion: PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Percutaneous sclerotherapy as endovascular treatment may cause severe complications beside the target area. Pulmonary embolism and thrombosis may occur. In this regard, our study aimed to reveal whether increasing systemic doses of polidocanol affects the coronary or pulmonary alveolar levels., Methods: Twenty-one Albino New Zealand rabbits, 7 rabbits per group, were used. The first group served as a control and received a 0.5 mL injection of saline; the second group received a single injection of 0.5 mL 1% polidocanol; and the third group received a single injection of 0.5 mL 2% polidocanol via the femoral vein. After anesthesia-induced decapitation on day 3, the experimental rabbits' lungs were removed in their entirety and sent to pathology for analysis. Micron-thick slices., Results: In all lung specimens of the first 2 groups, no narrowing or obstruction was detected in the pulmonary vessels in macroscopic and microscopic evaluation. No emphysematous changes or congestion were observed. In the third group's animal lungs, congestion in pulmonary vessels, emphysematous changes, and intra-alveolar hemorrhage were found., Conclusion: In our study, a single injection of 0.5 mL 2% polidocanol via the femoral vein. Animal lungs, congestion in pulmonary vessels, emphysematous changes, and intra-alveolar hemorrhage were found. As a result, our study demonstrated pulmonary vascular damage with increasing doses of polidocanol. So, the dose of polidocanol should be used in a limited manner., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chemodynamic therapy (CDT) is emerging as a promising treatment for biofilm infections. However, its effectiveness is significantly hindered by several factors: the body's stable temperature, a limited supply of Fe 2+ ions, and inadequate endogenous levels of H 2 O 2 at the infection sites. Herin, our study introduces MPN-crosslinked hyaluronic acid (HA) nanogels as an effective strategy for treating biofilm-associated infections. The DHA@HA-TA/Fe (DHTF) nanogel is synthesized through the coordination reaction between Fe 2+ ions and tannic acid (TA)-modified HA, with dihydroartemisinin (DHA) encapsulated within the structure. DHTF exhibits pH-/hyaluronidase-responsiveness in the biofilm infection microenvironment, enabling sustained release of DHA as a substitute for H 2 O 2 and Fe 2+ for CDT. The incorporation of Fe 2+ /TA-based MPN and DHA within the nanogels enables photothermal/DHA dually-enhanced CDT, facilitating efficient disruption of biofilm matrices and bacterial eradication through boosting reactive oxygen species production. In vivo studies demonstrate that DHTF exhibit prolonged retention within biofilms. This ensures a sustained release of therapeutic agents and continuous anti-biofilm activity. Eventually, both in vitro and in vivo evaluations consistently confirm the significant anti-biofilm capacity of DHTF. Our findings highlight the potential of DHTF as a promising nanomedicine for biofilm-related infections, offering efficient treatment strategies that could improve clinical management of these challenging conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite significant advancements in hydrogels in recent years, their application in corneal repair remains limited by several challenges, including unfitted curvatures, inferior mechanical properties, and insufficient reactive oxygen species (ROS)-scavenging activities. To address these issues, this study introduces a 3D-printed corneal scaffold with nanocomposite hydrogel consisting of gelatin methacrylate (GelMA), poly (ethylene glycol) diacrylate (PEGDA), Laponite, and dopamine. GelMA and PEGDA act as matrix materials with photo-crosslinking abilities. As a two-dimensional nanoclay, Laponite enhances the rheological properties of the hydrogel, making it suitable for 3D printing. Dopamine self-polymerizes into polydopamine (PDA), providing the hydrogel with ROS-scavenging activity. The incorporation of Laponite and the synergistic effect of PDA endow the hydrogel with good mechanical properties. In vitro investigations demonstrated the cytocompatibility of GelMA-PEGDA-Laponite-dopamine (GPLD) hydrogel and its ROS-scavenging activity. Furthermore, in vivo experiments using a rabbit model of lamellar keratoplasty showed accelerated corneal re-epithelialization and complete stromal repair after the implantation of the 3D-printed scaffold. Overall, due to its high bioactivity and simple preparation, the 3D-printed scaffold using GPLD hydrogel offers an alternative for corneal repair with potential for clinical translation. STATEMENT OF SIGNIFICANCE: The clinical application of hydrogel corneal scaffolds has been constrained by their inadequate mechanical properties and the complex microenvironment created by elevated levels of ROS post-transplantation. In this study, we developed a kind of nanocomposite hydrogel by integrating Laponite and dopamine into GelMA and PEGDA. This advanced hydrogel was utilized to 3D print a corneal scaffold with high mechanical strength and ROS-scavenging abilities. When applied to a rabbit model of lamellar keratoplasty, the 3D-printed scaffold enabled complete re-epithelialization of the cornea within one week. Three months after surgery, the corneal stroma was fully repaired, and regeneration of corneal nerve fibers was also observed. This 3D-printed scaffold demonstrated exceptional efficacy in repairing corneal defects with potential for clinical translation., Competing Interests: Declaration of competing interests The authors declare that they have no competing interests., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Inc. All rights reserved.)

Seeking effective ways to maintain cellular homeostasis is crucial to the survival of organisms when they encounter osmotic stress. Glycine betaine (GB) is a widely generated natural osmolyte, but its endogenous production and action are limited. Herein, a kind of nonionic surfactant dodecyl-β-d-glucopyranoside (DG) and a common polymer polyethylene glycol (PEG) are proven to have the ability to enhance the osmotic stress (induced by sugar concentration changes) tolerance of cell and organism models, those are giant unilamellar vesicles (GUVs) and gram-negative Escherichia coli. DG or PEG only induces small size decrease and certain shape change of GUVs. Importantly, DG or PEG at the concentration 100 times lower than that of GB effectively increases the survival rate of bacteria under both hypoosmotic and hyperosmotic conditions. This intriguing result is attributed to the insertion of DG or adsorption of PEG in the lipid bilayer membrane, leading to enhanced membrane permeability. These exogenous substances can replace GB to facilely and highly efficiently augment adaptation of organisms to osmotic stress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuchun Han, Yilin Wang reports financial support was provided by National Natural Science Foundation of China. Yilin Wang reports financial support was provided by Ministry of Science and Technology of the People’s Republic of China. Qing Shao reports a relationship with National Natural Science Foundation of China that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) exhibits a low response to immunotherapy due to the dense extracellular matrix (ECM) filled with immunosuppressive cells including dendritic cells (DCs) of blocked maturation. Herein, we develop a nanoprodrug self-assembled from polyethylene glycol-poly-4-borono-l-phenylalanine (mPEG-PBPA) conjugating with quercetin (QUE) via boronic ester bonds. In addition, an immune adjuvant of imiquimod (R837) is incorporated. The nanodrug (denoted as Q&R@NPs) is prepared from a simple mixing means with a high loading content of QUE reaching more than 30%. Owing to the acid and reactive oxygen species (ROS) sensitivities of boronic ester bonds, Q&R@NPs can respond to the tumor microenvironment (TME) and release QUE and R837 to synchronously exert multicellular regulation functions. Specifically, QUE inhibits the activation state of hepatic stellate cells and reduces highly expressed programmed death receptor ligand 1 (PD-L1) on tumor cells, meanwhile R837 exposes calreticulin on tumor cell surface as an "eat me" signal and leads to a large number of DCs maturing for enhanced antigen presentation. Consequently, the cooperative immune regulation results in a remodeled TME with high infiltration of cytotoxic T lymphocytes for enhanced HCC immunotherapy, which demonstrates an effective immunotherapy paradigm for dense ECM characterized solid tumors with high PD-L1 expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ferroptosis plays an important role in radiotherapy (RT), and the induction of ferroptosis can effectively sensitize radiotherapy. However, the therapeutic efficiency is always affected by ferroptosis resistance, especially SLC7A11 (Solute Carrier Family 7 Member 11)-cystine-cysteine-GSH (glutathione)-GPX4 (glutathione peroxidase 4) pathway-mediated resistance. In this study, tumor-microenvironment self-activated high-Z element-containing nanoferroptosis inducers, PEGylated Fe-Bi-SS metal-organic frameworks (FBSP MOFs), were developed to sensitize RT. Unexpectedly, ferroptosis-resistant SLC7A11 would be self-adaptively upregulated, leading to self-responsive ferroptosis resistance. Since the conversion from SLC7A11-transported cystine to cysteine is highly glucose-dependent, glucose oxidase (GOx) was incorporated in the MOFs, causing the depletion of NADPH (nicotinamide adenine dinucleotide phosphate) to terminate the conversion from cystine to cysteine, relieving the self-adaptive ferroptosis resistance. Excitingly, the accumulation of cystine would synergistically lead to disulfide stress and trigger disulfidptosis, making a new contribution to enhance therapeutic efficiency. Moreover, the hydrogen peroxide produced during glucose oxidation could also cascade-react with the Fenton reaction, therefore enhancing ferropotosis. Both in vitro and in vivo results suggested that therapeutic efficiency of ferroptosis-mediated radiosensitization could be enhanced benefiting from synergistic disulfidptosis induction, indicating that disulfidptosis might be an efficient strategy to relieve ferroptosis resistance and enhance RT efficiency.

Osseointegration is a crucial property of biomaterials used for bone defect repair. While titanium is the gold standard in craniofacial surgeries, various polymeric biomaterials are being explored as alternatives. However, polymeric materials can be bioinert, hindering integration with surrounding tissues. In this investigation, plasma ion immersion implantation (PIII)-treated polyether ether ketone (PEEK) and polyether ketone (PEK) implants were assessed in a sheep maxilla and mandible model. Defects were filled with PIII-treated PEEK and PEK implants, produced through fused filament fabrication (FFF) and selective laser sintering (SLS), respectively. Positive controls were grade 23 titanium implants via selective laser melting, while untreated PEEK implants served as negative controls. Surface analyses using scanning electron microscopy and atomic force microscopy revealed favorable properties. Osseointegration was qualitatively and quantitatively assessed at 8-, 10-, and 12-weeks post-implantation, showing significantly improved outcomes for both PIII-treated PEEK and PEK implants compared to untreated controls. The study suggests PIII treatment enhances FFF-printed PEEK's osseointegration, and PIII-treated SLS-printed PEK achieves comparable osseointegration to 3D printed titanium. These findings underscore surface modification strategies' potential for polymeric biomaterials, offering insights into developing alternative implant materials for craniofacial surgeries, with enhanced biocompatibility and osseointegration capabilities for improved clinical outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The continuous contamination of heavy metals (HMs) in our ecosystem due to industrialization, urbanization and other anthropogenic activities has become a serious environmental constraint to successful crop production. Lead (Pb) toxicity causes ionic, oxidative and osmotic injuries which induce various morphological, physiological, metabolic and molecular abnormalities in plants. Polyethylene glycol (PEG) is widely used to elucidate drought stress induction and alleviation mechanisms in treated plants. Some recent studies have unveiled the potential of PEG in regulating plant growth and developmental procedures including seed germination, root and shoot growth and alleviating the detrimental impacts of abiotic stresses in plants. Therefore, the current study aimed to assess the effects of seed priming with various concentrations (10%, 20%, 30% and 40%) of PEG on the growth and development of radish plants growing under Pb stress (75 mg/kg soil). Lead toxicity reduced root growth (32.89%), shoot growth (32.81%), total chlorophyll (56.25%) and protein content (58.66%) in treated plants. Similarly, plants showed reduced biomass production of root (35.48%) and shoot (31.25%) under Pb stress, while 30% PEG seed priming enhanced biomass production of root (28.57%) and shoot (35.29%) under Pb contaminated regimes. On the other hand, seedlings obtained from 30% PEG priming demonstrated a notable augmentation in the concentrations of photosynthetic pigments, antioxidative activity and biomass accumulation of the plants. PEG-treated plants showed modulations in the enzymatic activities of peroxidase (PO), catalase (CAT) and superoxide dismutase (SOD). These changes collectively played a role in mitigating the adverse effects of Pb on plant physiology. Our data revealed that PEG interceded stress extenuation encompasses numerous regulatory mechanisms including scavenging of ROS through antioxidant and non-antioxidants, improved photosynthetic activity and appropriate nutrition. Hence, it becomes necessary to elucidate the beneficial role of PEG in developing approaches for improving plant growth and stress tolerance., Competing Interests: Naim Ahmad Yasin is an Academic Editor for PeerJ., (©2025 Sajid et al.)

The molecular link between stress and carcinogenesis and the positive outcomes of stress intervention in cancer therapy have recently been well documented. Cancer stem cells (CSCs) facilitate cancer malignancy, drug resistance, and relapse and, hence, have emerged as a new therapeutic target. Here, we aimed to investigate the effect of three previously described antistress compounds (triethylene glycol, TEG; Withanone, Wi-N, and Withaferin A, Wi-A) on the stemness and differentiation characteristics of cancer cells. Breast carcinoma, glioblastoma, and neuroblastoma cells were treated with a non-toxic concentration of TEG (0.1%), Wi-N (5 µM), and Wi-A (0.1 µM) in 2D and 3D cultures. The results demonstrated that TEG, Wi-N, and Wi-A suppressed the stemness properties, which was linked with their inhibition of epithelial-mesenchymal transition (EMT) signaling. In particular, Wi-N and TEG caused a stronger reduction in the self-renewal capability of CSCs than Wi-A, as evidenced by a tumor spheroid formation assay and analyses of stemness-related genes ( ALDH1 , CD44 , NANOG , CD133 , SOX2 ). Furthermore, TEG and Wi-N caused the differentiation of cancer cells. Each of these was supported by (i) the upregulation of KRT18 , KRT19 , E-cadherin , and downregulation of vimentin in breast carcinoma; (ii) increased levels of GFAP, MAP2, and PSD-95 in astrocytoma; and (iii) increased NeuN, GAP-43, and NF200 levels in neuroblastoma. Furthermore, a reduction in cancer progression-related proteins (PI3K, N-myc) was recorded in treated cells. Our results suggest that TEG and Wi-N may be recruited to target cancer cell stemness and differentiation therapy.

The secretion of glucagon-like peptide-1 (GLP-1) is promoted by various nutrients, and glucose and fructose stimulate GLP-1 secretion via intracellular metabolism. D-allulose (allulose), a nonmetabolizable epimer of D-fructose, is also effective in stimulating GLP-1 secretion, although its underlying mechanism remains unclear. We previously observed intestinal distension after the oral administration of allulose, accompanied by increased GLP-1 secretion in rats, possibly because of the low or slow absorbability of allulose. In this study, we sought to determine whether intestinal distension caused by allulose and other factors gives rise to GLP-1 secretion in rats. We found that the oral coadministration of carbonated water enhanced allulose-induced GLP-1 secretion. Polyethylene glycol 1000 and D-mannitol, which are water-soluble and poorly absorbable, stimulated GLP-1 secretion. However, cellulose (insoluble), and tetra ethylene glycol (water-soluble and absorbable) did not. The secretion of GLP-1 increased as the absolute amount of allulose increased, independent of the concentration. The extent of the GLP-1 secretory response was positively correlated with the intestinal content volume and diameter after allulose administration. Furthermore, the intraileal administration of air expanded the intestine-induced secretion of GLP-1. Our results demonstrate that allulose promotes GLP-1 secretion, at least in part, via intestinal distension as a novel GLP-1 secretory mechanism. Physical stimulation may also contribute to postprandial GLP-1 secretion., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Peg-IFNα is one of the current therapeutic strategies for Hepatitis B virus (HBV) seroclearance. Nevertheless, the underlying mechanisms are not yet adequately understood. The objective of this study was to explore the potential mechanisms using multiomics approach. For the first time, we revealed the transcriptomic, proteomic, and metabolomic characterizations of Peg-IFNα-induced HBsAg seroclearance. We found that Peg-IFNα caused significant changes during the treatment. Patients who achieved HBsAg seroclearance were characterized as having decreased transcriptional activity of genes involved in fatty acid metabolism and the glycolysis/gluconeogenesis pathway, with up-regulated expression of fatty acid degradation-related proteins. Consistently, mitochondrial TCA cycle metabolites, including citric, isocitric, and malic acids, were significantly elevated in patients who achieved HBsAg seroclearance. We also observed up-regulated transcriptional activity of NK cell-mediated cytotoxicity, positive regulation of B cell activation, immunoglobulin production, and T cell receptor complex in functional-cured patients. Conversely, the metabolites associated with unsaturated fatty acid biosynthesis were increased in HBsAg persistent patients, and the transcriptional activity of immunoglobulin production and T cell receptor complex was down-regulated after 48 weeks of Peg-IFNα treatment. Our findings provided valuable resources to better understand the process of HBsAg seroclearance and shed new light on the pathways to facilitate higher functional cure rates for CHB.

There is an emerging necessity for improved therapies against Candida-related infections, with significant implications for global healthcare. Current antifungal agents, limited in number, target specific pathways, but resistance remains a concern. Flucytosine (5FC) exhibits antifungal activity, particularly against Candida. However, monotherapy efficacy is limited, necessitating combination treatments. Herein, we report PEGylated squalene-based nanocarriers for 5FC loading, aiming to enhance its monotherapy efficacy against Candida strains. The loading of 5FC within micelles was achieved using the ultrasound-assisted solvent evaporation method. The 5FC-loaded micelles, together with non-loaded micelles, were thoroughly characterized and analyzed. STEM and DLS analysis confirmed the core-shell morphology with nanometric dimensions along with improved colloidal stability. The quantification of drug loading efficiency and drug loading capacity was calculated using the UV-Vis technique. The in vitro drug-release studies in simulated physiological conditions showed sustained release within 48 hours. Moreover, the release kinetics calculated using mathematical models showed a Fickian diffusion drug release mechanism in simulated physiological conditions with a slower diffusion rate. The in vitro antifungal activity was tested on Candida albicans, Candida glabrata, and Candida parapsilosis. The results showed improved antifungal activity for the nanotherapeutic and unchanged in vitro toxicity toward normal cells, suggesting promising advancements in 5FC therapy., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)

With the increasing aging population, the demand for orthopedic implants is also growing. Polyether ether ketone (PEEK) is considered a promising material for orthopedic implants due to its excellent biocompatibility. However, the lack of bioactivity and excessive immune response post-implantation often impair bone integration. Therefore, it is urgent to bio-functionalize PEEK-based implants to promote bone integration. This study employs a simple, economical, and feasible method to coat Ga-ion doped bioactive glass nanoparticles (Ga-MBGs) onto sulfonated PEEK surfaces, constructing a multifunctional PEEK-based orthopedic implant. The resulting bio-functionalized PEEK implants promote macrophage M2 phenotype polarization, thus fostering an anti-inflammatory immune microenvironment. Moreover, the direct osteogenic effect of Ga ions and the immuno-osteogenic effect through promoting macrophage M2 polarization enhance osteogenic differentiation potential in vitro and bone integration in vivo. A sequence of in vivo and in vitro experiments substantiates the essential and intricate function of this innovative orthopedic implants. in regulating normal bone immunity and metabolism. Overall, the application of Ga-MBGs provides a simple, economical, and effective method for developing multifunctional orthopedic implants. This surface bio-functionalized PEEK implant, capable of modulating immunity and bone metabolism, holds significant clinical application potential as an orthopedic implant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Osseointegration is significantly impeded in osteoporotic conditions due to the elevated levels of reactive oxygen species (ROS) and inflammation at the site of injury. To enhance bone regeneration in osteoporotic conditions, a modified polyether ether ketone (PEEK) implants was prepared, denoted as PEEK-PDA-Sr. The implants consisted of mussel adhesion layer with the conjugation of strontium (Sr) ions, which can constantly release Sr ions for up to 3 weeks. PEEK-PDA-Sr demonstrated excellent biocompatibility and effectively regulated intracellular ROS levels and macrophage differentiation. In addition, the PEEK-PDA-Sr facilitated the osteogenesis of bone marrow stromal cells (BMSCs). In the ovariectomized (OVX) rat model of osteoporosis, the PEEK-PDA-Sr exhibited raised osseointegration in the femoral bone defects. The PEEK-PDA-Sr can be used as an immunoregulator with enhanced osseointegration and osteogenesis both in vivo and in vitro, which provides an available approach to treat osteoporotic bone defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, poly(lactic acid) (PLA)-tetrapropylammonium chloride (TCL)-poly(ethylene glycol) (PEG) nonwoven networks were produced using PLA, PEG with different concentrations (3, 5, 7, and 9 wt%), and TCL. PEG is included as a plasticizer in PLA polymer, which has high biocompatibility but a brittle structure. The importance of this study is to investigate the effect of TCL salt on the characterization of PLA-PEG nanofibers. For this research, the cytotoxicity test system responsible for the fibroblast cell line (L929) was evaluated with the liquid absorption capacity (LAC) and drying time tests for its use in wound dressings. The addition of TCL salt reduced bead formation in PLA-PEG nanofibers and increased the homogeneity of fiber dispersion. The smoothest and most homogeneous nonwoven networks were obtained as PLA-5TCL-PEG. It was also reported that this nonwoven network exhibited liquid absorption behavior with a maximum increase of 150% compared to the PLA-PEG nonwoven network and had the highest Young's modulus value of 12.97 MPa. In addition to these tests, evaluations were made with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), drying time test, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and mechanical tests. In addition, high cell viability was observed in L292 mouse fibroblast cells at the end of the 24th hour, again with the effect of TCL salt. In addition, antibacterial activity was tested against gram-negative E. coli and gram-positive S. aureus bacteria, and it was observed that there was no antibacterial activity. Since PLA-TCL-PEG nonwoven webs have a maximum cell viability of 133.27%, they are recommended as a potential dermal wound dressing., (© 2024 The Author(s). Biopolymers published by Wiley Periodicals LLC.)

Peanut (Arachis hypogaea L.) is an important cash and oil seed crop, mostly distributed in arid and semi-arid areas. In recent years, due to the influence of atmospheric circulation anomalies and other factors, drought has become frequent and increasingly serious in China. This has posed serious challenges to peanut production. The objective of this study was to investigate the potential of the endophytic fungus Piriformospora indica to form a symbiotic relationship with peanut plants and to evaluate the drought tolerance of P. indica-colonized peanut plants subjected to a simulated drought stress treatment using 20% polyethylene glycol 6000 (PEG6000). The endophytic fungus P. indica affected the physiological characteristics of the host plant by colonizing the plant roots, thereby conferring greater resistance to drought stress. This fungus strongly colonized the roots of peanuts and was found to enhance root activity after 24 h of P. indica colonization under PEG6000. Catalase (CAT) and peroxidase (POD) activities were increased at 24 h in peanut leaves colonized with P. indica. Expression of drought-related genes, such as AhNCED1, AhP5CS, and DREB2A was upregulated at 24 h of P. indica colonization. In addition, after PEG6000 treatment, proline, soluble protein, and abscisic acid (ABA) concentrations in plants were increased, while the accumulation of malondialdehyde (MDA), and hydrogen peroxide (H 2 O 2 ) was decreased in P. indica colonized peanut. In conclusion, P. indica mediated peanut plant protection against the detrimental effects of drought resulted from enhanced antioxidant enzyme activities, and the upregulated expression of drought-related genes for lower membrane damage., (© 2024 Wiley‐VCH GmbH.)

Wound infections caused by microorganisms often give rise to extensive inflammation and vascular damage that compromise the wound healing process. Designing approaches to more effectively controlling wound infections and accelerating this healing process are urgently needed. This study was designed with the goal of synthesizing an injectable, double cross-linked hydrogel suitable for use when treating infected wounds. After initially synthesizing methacrylated polylysine (PLMA) through polylysine grafting with methacrylic anhydride, CGRP and PLMA were incorporated into a PEG hydrogel network through reactions between NHS-activated carboxyl esters and amino groups (NH₂). PLMA was also employed to enhance the self-crosslinking activity, culminating in the production of PEG/PLMA/CGRP double cross-linked hydrogels. After injection these hydrogels were capable of undergoing rapid molding such that they were able to conform to the irregularly shaped wound contours. This PEG/PLMA/CGRP formulation was capable of mimicking nerve ending-mediated CGRP secretion to control wound healing, while also exhibiting robust antioxidant, anti-inflammatory, and pro-angiogenic properties. In addition, PEG/PLMA/CGRP hydrogels in vitro showed robust resistance to S. aureus and E. coli. In a rat model of S. aureus-mediated wound infection, this hydrogel markedly promoted wound healing. PEG/PLMA/CGRP hydrogels are thus an effective tool for use in the context of infected wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano-PEGylated liposomes (Ber-Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti-oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1β and TNF-α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD, and IL-18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aβ] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase-1, GSDMD, IL-18 and Aβ deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI-induced aberrations in the measured parameters and improved the IMI-induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber-Lip., (© 2024 International Union of Biochemistry and Molecular Biology.)

Discectomy serves as the primary therapeutic approach for lumbar disc herniation, but the annular fibrosus defects after discectomy may lead to recurrence of disc herniation. Despite recent advances in bioinspired adhesives to seal the AF defect, the growing popularity of endoscopic discectomy has put forward high requirements for the tissue bioadhesives with rapid injectability, easy operation, and robust tissue adhesion in underwater environments. Herein, a rapidly in situ forming injectable tetra-PEG bioadhesive (ISG) comprising of FDA-approved tetra-armed poly (ethylene glycol) amine (tetra-PEG-NH 2 ) and tetra-armed poly (ethylene glycol) succinimidyl glutarate (tetra-PEG-SG) for the sutureless closure of AF defects, is reported. Relying on quick ammonolysis reaction between N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG polymer and amine groups of tetra-PEG-NH 2 polymer and tissue proteins, the uniform networks are formed within seconds with easy injection, efficient waterproofness, instant tissue adhesion, and durable compliance. The goat lumbar discectomy model was used to assess the effect of ISG hydrogels in vivo. The results reveal that the resultant ISG bioadhesive can effectively maintain the disc height, fuse with the host tissue, ameliorate IVD degeneration, and retain the initial biomechanics. Together, this study provides an efficient strategy of in situ injectable glue for the minimally invasive treatment of AF defects., (© 2024 Wiley‐VCH GmbH.)

Uncontrollable hemorrhage from trauma and open surgery leads to a high percentage of death. Even though some patch-type hemostatic materials have been used in the clinic, sufficient tissue adhesion property and the management of tissue adhesion and anti-adhesion have been the challenges. In this report, we designed Janus tissue adhesive hemostatic patch, consisting of Alaska pollock gelatin (Org-ApGltn) as a support layer and decanoyl group-modified ApGltn (C10-ApGltn) with pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG) as an adhesive layer, named as the C10-ApGltn patch. The C10-ApGltn patch adhered onto blood vessel surface by the activation 4S-PEG and hydrophobic groups in C10-ApGltn through the covalent bond formation and physical interaction. The burst strength of the C10-ApGltn patch was optimized in terms of the degree of substitution, the molecular weight of 4S-PEG, the concentration of C10-ApGltn, and the NHS/NH 2 ratio. The optimized C10-ApGltn patch showed significantly higher burst strength with commercially available TachoSil®. The C10-ApGltn patch showed enzymatic degradability in a buffer solution with collagenase. In a rat liver hemorrhage model, the C10-ApGltn patch acted as a sealant on the hemorrhage site and exhibited competitive hemostatic property to TachoSil®., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyetheretherketone (PEEK) has been broadly used in orthopedic implant devices. Nevertheless, the bioinert tended to cause implant loosening and bacterial infection in orthopedic and trauma surgery. In this study, a drug-laden chitosan coating (CS) was constructed and deposited on the porous surface of PEEK (CG-SPEEK) internal fixation plate for multi-functionalization. The physical characterizations of CG-SPEEK were further investigated in the morphology, hydrophilicity, surface energy, roughness, drug release and mechanical properties. CG-SPEEK exhibited excellent antibacterial capabilities in both Staphylococcus aureus and Escherichia coli compared to other groups. Besides, BMSCs cells showed better biocompatibility and certain osteogenic activity on composite coating in vitro. Furthermore, CG-SPEEK promoted bone regeneration to some extent and express certain effect against infections in vivo study. Overall, combining personalized design and modification is an innovative strategy to realized functionalization, which may have a strong potential in clinical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to assess the effect of an oscillating chitosan brush (OCB) compared with an ultrasonic device with PEEK tip (US-PEEK) for mechanical implant surface decontamination using an in vitro model combining 3D models and a validated dynamic multispecies biofilm., Materials and Methods: A multispecies biofilm using six bacterial strains (Streptococcus oralis, Veillonella parvula, Actinomyces naeslundii, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans) was seeded on dental implants with machined and sandblasted, large-grit and acid-etched (SLA) surfaces. These were installed in 3D models depicting peri-implant defect. Mechanical decontamination was performed for 120 s using either an OCB or a US-PEEK. A negative control group received no treatment. Scanning electron microscopy (SEM) was used to evaluate the bacterial composition and quantitative PCR (qPCR) analyzed the number of each bacterial species [colony-forming units per milliliter (CFU/mL)]., Results: Well-structured biofilms with a dense microbial distribution were observed on the negative control implants after 72 h. qPCR following mechanical decontamination showed a scarce bacterial reduction in the OCB group. The US-PEEK group exhibited a significant decrease in bacterial species compared to both OCB and control groups (p < 0.05). A biofilm removal effect was also observed in the OCB group for the machined implant surfaces., Conclusion: In vitro assessment using an anatomical 3D model showed that mechanical decontamination effectively reduced biofilm. The US-PEEK group demonstrated biofilm reduction on the SLA surface, while the OCB group showed a reduction on the machined implant surface. Additionally, the US-PEEK group demonstrated greater efficacy in reducing bacterial numbers., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study investigated the synergistic effects of reduced graphene oxide (RGO) on the antibacterial activity of three calcium hydroxide-based intracanal medicaments with different vehicles., Methods: Multispecies biofilms were cultured in a bovine root canal model. Intracanal medicaments containing nonaqueous vehicles, including N-methyl-2-pyrrolidone (NMP; CleaniCal), propylene glycol (PG; UltraCal XS), and polyethylene glycol (PEG; Calcipex II), were placed in the model. The synergistic effects of RGO were evaluated by analyzing colony-forming units, extracellular deoxyribonucleic acid (eDNA) levels, and findings from confocal laser-scanning microscopy (CLSM) and scanning electron microscopy. To evaluate the cytotoxicity of each vehicle, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. To determine whether RGO altered the physicochemical properties of the medicaments, flowability and pH were measured. A P-value of <0.05 was considered to indicate statistical significance., Results: In the CleaniCal group, bacterial viability, eDNA levels, and extracellular polymeric substrate (EPS) were significantly lower in the presence of RGO. However, only bacterial viability significantly differed in the other groups. PEG resulted in the highest cell viability among the vehicles. Furthermore, there was no significant difference in flowability or pH in relation to the inclusion of RGO., Conclusion: The results suggest that RGO enhances the antibacterial effect of intracanal medicaments containing NMP.

This study aimed to evaluate the role of drought-induced changes in the effects of cadmium (Cd) in plants. Cd is the most hazardous and important environmental pollutant. Water deficit is the most common environmental stress encountered by plants and affects most of the plant functions. The present study assessed the effect of Cd and water deficit on Capsicum frutescens seedlings in single and combined treatments. The seedlings of Capsicum were grown in a hydroponic solution and treated with Cd. The seedlings were subjected to water deficit with the help of polyethylene glycol (PEG). The other set of seedlings was treated with combined Cd + PEG. In the absence of PEG, maximum Cd accumulation was observed. The root and shoot growth of the seedlings were affected under all treatments with maximum inhibition in Cd. Pigment, protein and sugar contents and nitrate reductase activity decreased significantly in all treatments, while proline content increased. Induction of oxidative damage occurred through the formation of free radicals which caused alteration in electrolyte leakage, lipid peroxidation and activities of antioxidant enzymes, viz. superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase and non-enzymatic non-protein thiol content and ascorbic acid in the stressed seedlings. Water deficit buttressed the toxic effect of Cd on chilli seedlings., Competing Interests: Declarations. Conflicts of Interest: This article does not contain any studies with human participants performed by any of the authors. All authors express their consent to publish the article. The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Our study aimed to assess the effects of anticancer 4-thiazolidinone-based free water-insoluble therapeutics Les-3288 and Les-3833 and their waterborne complexes with branched PEG-containing polymeric carriers (A24-PEG550 and A24-PEG750) on immune response., Methods: Human peripheral blood was used to study in vitro lymphocyte proliferative function, leukocyte phagocytic activity and respiratory burst, and cytokine production., Results: The binding of the polymer to the anticancer drug Les-3288, which is intended to mitigate the immunosuppressive effects of the free drug on the proliferative activity of T lymphocytes and T-dependent B cells, demonstrated comparable efficacy for both A24-PEG750 and A24-PEG550 nanocarriers. Furthermore, it was observed that the drug-polymer complex significantly increased the reduced levels of IFN-γ and TNF-α resulting from free Les-3288. Conversely, the reduced levels of IL-6 and IL-4 remained unchanged. Administration of either form of Les-3288 had no effect on the phagocytic activity of monocytes, granulocytes or the respiratory burst of granulocytes. Due to the reduced cell viability and increased cytotoxicity associated with Les-3833, tenfold lower doses were selected for the immune assays. The effects of free Les-3833 on lymphocyte proliferative function resulted in significant stimulation of T-dependent B cells. The binding of Les-3833 to the smaller carrier, A24-PEG550 was found to maintain the stimulatory effect on B lymphocytes. While no effect of free Les-3833 on the granulocyte phagocytic activity was observed, binding of Les-3833 to both polymeric carriers resulted in a decrease in granulocyte phagocytic activity and respiratory burst, with no observable effect on monocytes. Monitoring of cytokine production showed no significant effect of either form of Les-3833 on the production of IFN-γ and IL-6. In the context of TNF-α and IL-4, the positive effect of polymer binding on restoring suppressed cytokine levels induced by the Les-3833 free drug was slightly more favorable for A24-PEG750., Conclusion: The drug complexation with novel PEGylated carriers is a promising way for efficient therapeutic development., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Tulinska et al.)

Extracellular vesicles (EVs) have been widely recognized as a heterogeneous group of membrane-coated submicrometer particles released by different types of cells, including stem cells (SCs). Due to their ability to harbor and transfer bioactive cargo into the recipient cells, EVs have been reported as important paracrine factors involved in the regulation of a variety of biological processes. Growing data demonstrate that EVs may serve as potential next-generation cell-free therapeutic factors. However, clinical application of EVs in tissue regeneration requires the development of standardized procedures for their long-term storage, without the loss of structural integrity and biological activity. In the current study, we developed a procedure of EV cryoprotection based on coating them with ultrathin polyelectrolyte bilayer consisting of cationic poly(ethylene glycol)- block - poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PEGn- b -PMAPTACm) and anionic of poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS). Based on the nanoparticle tracking analysis, high-resolution flow cytometry, and mass spectrometry, we studied the vesicle integrity following single- or multiple freezing-thawing cycles and long-term storage. Additionally, we evaluated the effect of cryopreservation on the EVs functional activity in vitro. Obtained data indicate that coating with polyelectrolytes improves the structural integrity of EVs and preserves their biological activity in vitro. Additionally, proteomic analysis confirmed the effect of particle stabilization, as well as an enrichment in EV proteins in samples cryopreserved in the presence of tested polymers. Taking together, our study indicates that the application of polyelectrolytes may be a novel, effective way of facilitating long-term storage of EV preparations for their further use in the biomedical applications.

Background: Osteoarthritis (OA) is a degenerative joint disease that leads to a substantial decline in the well-being of older individuals. Chondrocyte senescence and the resultant damage to cartilage tissue, induced by elevated levels of reactive oxygen species within the joint cavity, are significant causative factors in OA development. Cerium oxide nanoparticles (CeONPs) present a promising avenue for therapeutic investigation due to their exceptional antioxidant properties. However, the limited effectiveness of drugs in the joint cavity is often attributed to their rapid clearance by synovial fluid., Methods: Polyethylene glycol-packed CeONPs (PEG-CeONPs) were synthesized and subsequently modified with the cartilage-targeting peptide WYRGRLGK (WY-PEG-CeO). The antioxidant free radical activity and the mimetic enzyme activity of PEG-CeONPs and WY-PEG-CeO were detected. The impact of WY-PEG-CeO on chondrocytes oxidative stress, cellular senescence, and extracellular matrix degradation was assessed using in vitro assays. The cartilage targeting and protective effects were explored in animal models., Results: WY-PEG-CeO demonstrated significant efficacy in inhibiting oxidative stress, cellular senescence, and extracellular matrix degradation in OA chondrocytes. The underlying mechanism involves the inhibition of the PI3K/AKT and MAPK signaling pathways. Animal models further revealed that WY-PEG-CeO exhibited a prolonged residence time and enhanced penetration efficiency in cartilage tissue, leading to the attenuation of pathological changes in OA., Conclusions: These findings suggest that WY-PEG-CeO exerts therapeutic effects in OA by inhibiting oxidative stress and suppressing the over-activation of PI3K/AKT and MAPK signaling pathways. This investigation served as a fundamental step towards the advancement of CeONPs-based interventions, providing potential strategies for the treatment of OA., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Laboratory Animal Welfare & Ethics Committee of the Renmin Hospital of Wuhan University (Approval No: 20230101 A) and conducted in compliance with the National Research Council’s Guide for the Care and Use of Laboratory Animals. Consent for publication: All authors have seen the manuscript and approved the submission. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Cardiovascular and renal complications of type 2 diabetes are the main causes of death in diabetic patients. Clinical studies have found that polyethylene glycol loxenatide (PEG-Loxe), a GLP-1 analog widely used to treat type 2 diabetes, boosts renal and cardiac functions in diabetic patients. However, its mechanism of action remains to be elucidated., Methods: Using injury models of HK-2 human renal proximal tubular epithelial cells and H9C2 rat myocardial cells, as well as db/db mouse models of type 2 diabetes, this study assessed the protective effects of PEG-Loxe on T2DM mice kidneys and hearts and revealed their mechanisms of action., Results: PEG-Loxe treatment significantly reduced the contents of serum creatinine, urea nitrogen, and 24 h urine protein, alleviated glomerular injury and inflammatory reaction, markedly elevated cardiac left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) levels, diminished pathological injuries in cardiac tissues, and improved renal and cardiac functions in db/db mice. In addition, PEG-Loxe considerably decreased the GRP78 mRNA and protein expressions of GRP78, p-eIF2α, ATF4, and CHOP in the kidneys of T2DM mice, inhibited GRP78/PERK/eIF2α pathway-related proteins in HK-2 cells cultured in high glucose concentrations, subdued renal endoplasmic reticulum stress, and eased renal injury in T2DM mice. PEG-Loxe also obstructed the TLR4/NF-κB inflammatory pathway and myocardial apoptosis and mitigated cardiac trauma in T2DM by reducing TLR4, MyD88, and p-NF-κBp65 protein expressions in cardiac tissues. The H9C2 cell experiment further confirmed PEG-Loxe's ability to protect the cardiovascular system of T2DM patients by inhibiting the TLR4/NF-κB inflammatory pathway and lessening LDH and CK-MB levels., Conclusion: We showed that PEG-Loxe could decrease renal stress response and improve renal injury in T2DM by inhibiting endoplasmic reticulum stress via the GRP78/PERK/eIF2α pathway. Additionally, PEG-Loxe could hinder the TLR4/NF-κB inflammatory pathway and myocardial apoptosis and boost cardiac function, thus exerting protective effects on the cardiovascular system in T2DM., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved (No. 20220102–05) by the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. The animal care and experimental procedures were carried out in accordance with the Guidelines of the Institutional Animal Care and Use Committee of Tongji Medical College and the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The crowded milieu of a biological cell significantly impacts protein aggregation and interactions. Understanding the effects of macromolecular crowding on the aggregation and fibrillation of amyloidogenic proteins is crucial for the treatment of many amyloid-related disorders. Most in vitro studies of protein amyloid formation and its inhibition by small molecules are conducted in dilute buffers, which do not mimic the complexity of the cellular environment. In this study, we used PEGs to simulate macromolecular crowding and examined the inhibitory effects of flavones DHF, baicalein, and luteolin on human lysozyme (HuL) aggregation at pH 2. Naturally occurring flavones have been effective inhibitors of amyloid formation in some proteins. Our findings indicate that while flavones inhibit HuL aggregation and fibrillation in dilute buffer solutions, complete inhibition is observed with a combination of flavones and PEGs, as shown by ThT fluorescence, light scattering, TEM, and AFM studies. The species formed in the presence of PEG 8000 and flavones were less hydrophobic, less toxic, and α-helix-rich compared to control samples, which were hydrophobic and β-sheet-rich, as demonstrated by ANS hydrophobicity, MTT assay, and CD spectroscopy. Fluorescence titration studies of flavones with HuL showed a significant increase in binding constant values under crowding conditions. These findings highlight the importance of macromolecular crowding in modulating protein aggregation and amyloid inhibition. Further studies using disease-causing mutants of HuL and other amyloidogenic proteins are needed to explore the role of macromolecular crowding in small-molecule-mediated modulation and inhibition of protein aggregation and amyloid formation.

Purpose: Given the increased use of polyethylene glycol (PEG) in refining the therapeutic activity of medicines, our research focuses on explaining the potential mechanism of immune reactions associated with this polymer. We aim to investigate the interaction of different types of PEG with mouse and human immune cells, thereby contributing to understanding PEG interactions with the immune system and verifying the proinflammatory activity of the tested polymers., Patients and Methods: Mouse macrophage and neutrophil cell lines, human peripheral blood mononuclear cells, and polymorphonuclear cells isolated from healthy donors were exposed to various PEGs. ROS, NO, and cytokine production were analyzed using fluorescence intensity, absorbance, or cytometric measurements. Toll-like receptor (TLR) signaling was verified using HEK-blue-reporter cell lines. Finally, neutrophil trap formation was studied using immunofluorescence labeling, and calcium imaging was performed using a Ca 2+ -sensitive indicator and fluorescence microscope., Results: Our findings show that specific PEG and mPEG are not toxic to tested mouse and human cells. However, they exert proinflammatory activity against human immune cells, as evidenced by the increased secretion of proinflammatory cytokines, such as IFN-a2, IFN-γ, TNF-α, MCP-1, IL-8, IL-17A, and IL-23. This phenomenon is independent of PEG signaling via TLR. Additionally, mPEG10 induced the formation of neutrophil extracellular traps and intracellular calcium signaling., Conclusion: Our finding suggests that some PEG types have proinflammatory activity against human immune cells, manifesting in the upregulated production of cytokines and neutrophils trap releasing., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hinz et al.)

The study aimed to evaluate bone repair using three osteoinductive polymers in bone defects created in rabbit tibias. Forty-eight adult rabbits were assessed at various time points: three, seven, fourteen, and thirty days. The groups included a control group (without biomaterial), M1 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol), M2 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol/β-Tricalcium Phosphate), and M3 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol/nano hydroxyapatite). Histomorphometric analysis was conducted to evaluate new bone formation within and around the bone defect. At 14 (p<0.05) and 30 days (p<0.05), the callus area in the membrane groups, particularly in M3, was also significantly larger than in the control group, indicating the osteoinductive potential of these biomaterials. The callus consisted of both bone and cartilaginous matrix, suggesting a robust activation of endochondral ossification. The number of osteoclast was higher in the membrane groups, especially at 14 days in the M3 group, indicating increased bone remodeling activity. The membranes were not fully absorbed by 30 days, creating a space between the defect and the periosteum. In conclusion, all three membranes showed significant chondro and osteoinductive potential, with the membrane containing nano-hydroxyapatite demonstrating the most pronounced potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 da Cunha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Considering the fact that resin infiltrants lack antibacterial activity, this study assessed the influence of the quaternary ammonium monomer dimethylaminohexadecyl methacrylate (DMAHDM) and amorphous calcium phosphate nanoparticles (NACP) on the physical and antibacterial properties of an experimental resin infiltrant (ERI)., Methodology: The following groups were established: ERI (75/25 wt.% TEGDMA/BISEMA), ERI + 2.5% DMAHDM (2.5DM), ERI + 5% DMAHDM (5DM), ERI + 2% NACP (NACP), ERI + 2.5% DMAHDM + 2% NACP (2.5DM&#95;NACP), ERI + 5% DMAHDM + 2% NACP (5DM&#95;NACP), and Icon® (IC), a commercial resin infiltrant. Degree of conversion (DC; n=4), sorption and solubility (SO/SOL; n=8), and contact angle (CA; n=10) tests were conducted. Biofilm biomass (BB; n=6) and bacterial metabolism (BM; n=8) were evaluated after Streptococcus mutans (UA159) cultivation for 48 h on material samples. Data were evaluated by one-way ANOVA and Tukey or Games-Howell post hoc tests (α=0.05)., Results: IC exhibited the highest DC, with no difference from 2.5DM and 5DM. IC showed the lowest CA. IC had the lowest SO, followed by ERI, which had the lowest SOL, with no difference from IC. 5DM&#95;NACP showed the lowest biofilm biomass, similar to 2.5DM and 5DM. Resin infiltrants containing DMAHDM showed reduced bacterial metabolism., Conclusions: DMAHDM, with or without NACP, demonstrated significant antibacterial activity, while NACP impaired DC. Both DMAHDM and NACP increased the contact angle, sorption, and solubility of the resin infiltrant, which may affect the material's clinical performance.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) staining revealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The efficacy of entomopathogenic fungi as pest control agents is constrained by both their physiological state and external environmental factors. This study identified synergists capable of enhancing the insecticidal activity of Beauveria bassiana (Bb) and investigated the underlying synergistic mechanisms. Our results found that among 6 potential synergists, polyethylene glycol 400 (PEG) and trehalose significantly improved Bb's lethality against Hyphantria cunea larvae, with PEG demonstrating the most pronounced effect. PEG treatment markedly increased Bb spore adhesion and germination rates, while spore hydrophobicity and growth rates remained unaffected. Moreover, PEG-treated spores exhibited higher thermal tolerance compared to untreated ones. In the Bb + PEG treatment group, the hemocyte count, encapsulation and melanization activities, and the expression of related regulatory genes were significantly lower than those in the Bb treatment group. Additionally, pathogen recognition, signal transduction, and humoral immunity effector genes expression were markedly suppressed in the Bb + PEG group. A significant reduction in the content of total amino acids, free fatty acids, glucose, and trehalose, alongside decreased expression of key regulatory genes in the tricarboxylic acid cycle and glycolysis pathways, was observed in the Bb + PEG treatment group. Furthermore, PEG enhanced Bb-induced apoptosis in H. cunea larvae, as evidenced by the upregulation of apoptosis-related genes. Notably, PEG alone did not significantly impact the innate immunity, energy metabolism, or apoptosis in H. cunea larvae. Overall, PEG exhibits considerable potential in amplifying Bb's insecticidal activity by directly optimizing spore performance and indirectly modulating the larvae's innate immunity, energy metabolism, and apoptosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Brassica napus L. plants are sensitive to water stress conditions throughout their life cycle from seed germination to seed setting. This study aims at identifying quantitative trait loci (QTL) linked to B. napus tolerance to water stress mimicked by applications of 10% polyethylene glycol-6000 (PEG-6000). Two doubled haploid populations, each consisting of 150 genotypes, were used for this research. Plants at the two true leaf stage of development were grown in the absence (control) or presence (stress) of PEG-6000 under controlled environmental conditions for 48 h, and the drought stress index was calculated for each genotype. All genotypes, along with their parents, were genotyped using the Brassica Infinium 90K SNP BeadChip Array. Inclusive composite interval mapping was used to identify QTL. Six QTL and 12 putative QTL associated with water stress tolerance were identified across six chromosomes (A2, A3, A4, A9, C3, and C7). Collectively, 2154 candidate genes for water stress tolerance were identified for all the identified QTL. Among them, 213 genes were identified as being directly associated with water stress (imposed by PEG-6000) tolerance based on nine functional annotations. These results can be incorporated into future breeding initiatives to select plant material with the ability to cope effectively with water stress., Competing Interests: The authors declare there are no competing interests.

Aggregation-induced emission (AIE) materials are attracting great attention in biomedical fields such as sensors, bioimaging, and cancer treatment, et al. due to their strong fluorescence emission in the aggregated state. In this contribution, a series of tetraphenylene-acetonitrile AIE compounds with D-A-D' structures were synthesized by Suzuki coupling reaction and Knoevenagel condensation, and their relationship of chemical structure and fluorescence properties was investigated in detail, among which TPPA compound was selected as the monomer owing to the longest emission wavelength at about 530 nm with low energy band gap ΔE 3.09 eV of neutral TPPA and 1.43 eV of protonated TPPA. Novel amphiphilic AIE PEG-TA copolymers were prepared by RAFT polymerization of TPPA and PEGMA with about 1.44×10 4 M w and narrow PDI, and the molar ratio of TPPA in the PEG-TA1 and PEG-TA2 copolymers was about 23.4 % and 29.6 %. The as-prepared PEG-TA copolymers would self-assembled in aqueous solution to form core-shell structures with a diameter of 150-200 nm, and their emission wavelength could reversibly convert from 545 nm to 650 nm with excellent pH sensitivity. The CLSM images showed that the PEG-TA FONs and PTX drugs-loaded PTX-TA FONs could be endocytosed by cells and mainly enriched in the cytoplasm, and CCK-8 results showed that the PEG-TA FONs had excellent biocompatibility but PTX-TA FONs had high inhibition ratio for A549 cells, moreover, the flow cytometry also showed that PTX-TA FONs could result in the apoptosis of A549 cells with some extent anti-tumor effect., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest or personal relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hemostatic powders are widely used in incompressible or irregularly shaped bleeding wounds, but traditional hemostatic powders exhibit low adhesion, unsatisfactory hemostatic effect, limited infection control, and are not suitable for clinical or emergency situations. This study developed a novel self-gelling hemostatic powder (QTPM) consisting of quaternized cellulose (QC)/ tannic acid (TA)/ polyethylene glycol (PEG)/ montmorillonite (MMT). QTPM could absorb interfacial liquid hydrating to a stable hydrogel which form a switchable adhesion to tissues. Moreover, QTPM exhibits excellent antibacterial property by the synergistic effect of QC and TA. Furthermore, QTPM directly activate intrinsic and extrinsic coagulation hemostatic pathways to enhance hemostasis, and it concentrate coagulation factors. In vivo hemostasis study results show that QTPM significantly accelerated hemostasis and reduced blood loss compared with the blank group (>75 % reduction in hemostatic time, >85 % reduction in blood loss) in liver bleeding model (hemostasis time of 71.67 ± 7.09 s, blood loss of 19.23 ± 2.60 mg) and tail amputation model (hemostasis time of 91.03 ± 12.05 s, blood loss of 15.24 ± 1.77 mg). Therefore, the advantages of QTPM including rapid and effective hemostasis, easy usage, easy storability and adaptability make it a potential biomaterial for rapid hemostasis direction in the clinical setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Significance: This study investigates the synergistic antitumor effect of PEG-BCT-100, an arginase, in clinical trials, with canavanine in pancreatic cancer, in vitro and in vivo. The treatment induces cancer cell apoptosis while sparing normal fibroblasts. Our findings suggest heightened susceptibility of pancreatic tumors deficient in arginine biosynthesis enzymes ASS1 and OTC., (©2024 The Authors; Published by the American Association for Cancer Research.)