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Tin-free self-polishing antifouling coatings have the highest market share since organotin self-polishing antifouling coatings have been banned. However, its high dependence on cuprous oxide was found to have caused potential harm to the environment, making it necessary to improve the functionality of the resin. In this paper, a zinc acrylate resin with side chain hanging indole derivative structure was prepared by using N-(1H-5-bromoindole-3-methylene) (BIAM) with good biological activity as functional monomer. The functional resin with good antifouling performance was selected by antibacterial and algae inhibition experiments. The results showed that when the BIAM content was 9 %, the inhibition rates of the resin on E. coli and Prymnesium parvum reached 98 % and 90 %, respectively. Tin-free self-polishing antifouling coatings were prepared using the above resins as film-forming materials. The anti-protein adsorption performance and antifouling performance of the coating were tested by anti-protein adsorption experiment and real sea hanging plate experiment. The results showed that the coating containing indole derivative structure had good anti-protein adsorption performance and antifouling performance, and the higher the BIAM content, the better the anti-protein adsorption performance and marine antifouling performance., 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.)

A novel composite hydrogel prepared from polyacrylamide (PAM), polydopamine-modified montmorillonite (PDA@MMT), graphene and hydroxypropyl cellulose (HPC), loaded with Ag NPs, was prepared for the catalytic degradation of methylene blue (MB) and Congo red (CR) using in situ reduction. HPC significantly enhanced the dispersion of PDA@MMT within the hydrogel, endowing the hydrogel with excellent mechanical properties, with stress and strain of 1773 kPa and 4005 %, and elastic modulus and toughness of 43.4 kPa and 29.54 MJ/m 3 , respectively. The introduction of graphene (GN) increased the rate of electron transfer during the catalytic process and significantly improved the catalytic efficiency, with catalytic rate constants of 1.360 and 0.803 min -1 for MB and CR at 20 °C, respectively. The hydrogels were endowed with excellent antimicrobial properties due to the introduction of Ag NPs. In the future, this hydrogel is expected to play an important role in environmental pollution control., 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.)

This study investigates the efficacy of a novel tissue-engineered scaffold for nerve repair and functional reconstruction following injury. Utilizing stable jet electrospinning, we fabricated aligned ultrafine fibers from dopamine and poly(L-lactic acid) (PLLA), further developing a biomimetic, oriented, and electroactive scaffold comprising poly(pyrrole) (PPy), polydopamine (PDA), and PLLA through dual in situ polymerizations. The scaffold demonstrated enhanced cell adhesion and reactive oxygen species (ROS) scavenging capabilities and promoted the differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells, essential for nerve regeneration. In vivo assessments revealed significant peripheral nerve regeneration in 10 mm sciatic nerve defects in rats, with observations made 12 weeks post-transplantation. This included facilitated myelination and increased muscle density on the injured side, leading to improved motor function recovery. Our results suggest that the aligned PPy/PDA/PLLA fibrous scaffold offers a promising approach for promoting the differentiation of MSCs into Schwann-like cells conducive to nerve regeneration and represents a significant advancement in nerve repair technologies. This study provides a foundational basis for future research into tissue-engineered solutions for nerve damage, potentially impacting clinical strategies for nerve reconstruction., 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.)

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice., 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.)

Oral mucosal lesions (OML), which represent a major public health issue worldwide, include any pathological changes in the oral mucosa, such as ulcers, pigmentation, and swelling. Due to its humid and dynamic complex environment, designing oral mucosal preparations poses significant challenges. Drawing inspiration from mussels, this study employed an eco-friendly one-pot strategy for the preparation of chitosan/polydopamine (CS/PDA) films. We demonstrated that CS-induced polymerization of dopamine monomers under acidic conditions, which might be attributed to the large number of hydrogen bonding sites of CS chains. PDA markedly enhances properties of the CS film and exhibits concentration dependence. At the concentration of 1 wt% PDA, the lap-shear strength and tensile strength of CS/PDA films reached 5.01 ± 0.24 kpa and 4.20 ± 0.78 kpa, respectively, indicating that the mucosal adhesion ability was significantly improved. In comparison with the single CS film, the swelling rate of CS/PDA film decreased by about 30 %. Rheological results also showed that the storage modulus returned to 93 % after cyclic large strain, while the single CS film only recovered to 73 %. Moreover, these films demonstrated good biocompatibility and enhanced oral ulcer healing in rats, providing a new and practical option for the local treatment of OML., 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.)

Nitrogen (N 2 ) conversion to ammonia (NH 3 ) in a mild condition is a big chemical challenge. The whole-cell diazotrophs based biological NH 3 synthesis is one of the most promising strategies. Herein, the first attempt of photoelectrochemical-microbial (PEC-MB) biohybrid is contributed for artificial N 2 fixation, where Azotobacter vinelandii (A. vinelandii) is interfaced directly with polydopamine encapsulated nickel oxide (NiO) nanosheets (NiO@PDA). By virtue of excellent bio-adhesive activity, high conductivity, and good biocompatibility of PDA layer, abundant A. vinelandii are effectively adsorbed on NiO@PDA to form NiO@PDA/A. vinelandii biohybrid, and the rationally designed biohybrid achieved a record-high NH 3 production yield of 1.85   µmol h -1 /10 8 cells (4.14 µmol h -1 cm -2 ). In addition, this biohybrid can operate both under illumination with a PEC model or in dark with an electrocatalytic (EC) model to implement long-term and successional NH 3 synthesis. The enhancement mechanism of NH 3 synthesis in NiO@PDA/A. vinelandii biohybrid can be ascribed to the increase of nicotinamide adenine dinucleotide-hydrogen (NADH) and adenosine 5-triphosphate (ATP) concentrations and over expression of nitrogen-fixing genes of nifH, nifD and nifK in nitrogenase. This innovative PEC-MB biohybrid strategy sheds light on the fundamental mechanism and establishes proof of concept of biotic-abiotic photosynthetic systems for sustainable chemical production., (© 2024 Wiley‐VCH GmbH.)

Breast cancer is the most prevalent cancer among women globally, with triple-negative breast cancer (TNBC) associated with poor prognosis and low five-year survival rates. Schiff base compounds, known for their extensive pharmacological activities, have garnered significant attention in cancer drug research. This study aimed to evaluate the anticancer potential of a novel β-diiminato compound and elucidate its mechanism of action. The compound's effect on cell viability was assessed using MTT assays in breast cancer cell lines including MCF-7 and MDA-MB-231. Cytotoxic effects were further analyzed using trypan blue exclusion and lactate dehydrogenase (LDH) release assays. In order to assess the mechanism of inhibitory activity and mode of cell death induced by this compound, flow cytometry of cell cycle distribution and apoptosis analysis were carried out. Apoptosis incidence was initially assessed through cell and nuclear morphological changes (Hoechst 33342/Propidium iodide (PI) staining) and further confirmed by Annexin V/PI staining and flow cytometry analysis. In addition, the effect of this compound on the disruption of mitochondrial membrane potential (MMP) and generation of the reactive oxygen species (ROS) was determined using the JC-1 indicator and DCFDA dye, respectively. The results demonstrated that the 24 h treatment with β-diiminato compound significantly suppressed the viability of MDA-MB-231 and MCF-7 cancer cells in a dose-dependent manner with the IC 50 value of 2.41 ± 0.29 and 3.51 ± 0.14, respectively. The cytotoxic effect of the compound was further confirmed with a dose-dependent increase in the number of dead cells and enhanced LDH level in the culture medium. This compound exerted its anti-proliferative effect by G2/M phase cell growth arrest in MDA-MB-231 breast cancer cells and induced apoptosis-mediated cell death, which involved characteristic changes in cell and nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased ROS level. Neither hepatotoxicity nor nephrotoxicity was detected in the biochemical and histopathological analysis confirming the safety characterization of this compound usage. Therefore, the results significantly confirmed the potential anticancer activity of a novel β-diiminato compound, as evidenced by the induction of cell cycle arrest and apoptosis, which might be driven by the ROS‑mediated mitochondrial death pathway. This compound can be a promising candidate for future anticancer drug design and TNBC treatment, and further preclinical and clinical studies are warranted., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn 2+ , Al 3+ , or Ga 3+ . Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

The SARS-CoV-2 main protease (Mpro) is an essential enzyme that promotes viral transcription and replication. Mpro conserved nature in different variants and its nonoverlapping nature with human proteases make it an attractive target for therapeutic intervention against SARS-CoV-2. In this work, the interaction mechanism between Mpro and diindolylmethane derivatives was investigated by molecular docking, enzymatic inhibition assay, UV-vis, fluorescence spectroscopy, and circular dichroism spectroscopy. Results of IC 50 values show that 1p (9.87 μM) was the strongest inhibitor for Mpro in this work, which significantly inhibited the activity of Mpro. The binding constant (4.07 × 10 5  Lmol -1 ), the quenching constant (5.41 × 10 5  Lmol -1 ), and thermodynamic parameters indicated that the quenching mode of 1p was static quenching, and the main driving forces between 1p and Mpro are hydrogen bond and van der Waals force. The influence of molecular structure on the binding is investigated. Chlorine atoms and methoxy groups are favorable for the diindolylmethane derivative inhibitors of Mpro. This work confirms the changes in the microenvironment of Mpro by 1p, and provides clues for the design of potential inhibitors., (© 2024 John Wiley & Sons Ltd.)

Achieving interfacial compatibility through sustainable methods is a key objective in natural fiber-plastic composites research, aimed at optimizing mechanical performance. This study introduced an innovative organic bamboo-plastic composite (BPC) interfacial layer, incorporating O-acylated chitin fibers densely coated with polydopamine (PDA) via a mild and facile self-assembly method. Chitin nanofibers were acylated with dodecenylsuccinic anhydride in a deep eutectic solvent in a one-pot process. The resulting BPCs exhibited significantly enhanced mechanical properties, with tensile strength, flexural strength, modulus, and impact strength increased by 73.64 %, 39.19 %, 15.42 %, and 63.57 %, respectively, compared to untreated BPCs. This improvement highlights the effectiveness of tailoring cross-linked networks across heterogeneous interfaces in providing strength, dissipating strain, and promoting interfacial compatibility. Furthermore, these modified BPCs demonstrated enhanced thermal stability, crystallization behavior, and moderate hydrophobicity. This surface treatment strategy offers a distinctive approach to producing high-performance, eco-friendly BPCs, also facilitating the processing and utilization of marine biological resources on a wide scale., 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.)

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPT x ) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDA n @TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDA n @TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPT x hydrogel platform has great potential for treating diabetic wounds., 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.)

This work introduces rationally designed, improved amphiphilic single-chain polymer nanoparticles (SCNPs) for imaging and photodynamic therapy (PDT) in zebrafish embryo xenografts. SCNPs are ultrasmall polymeric nanoparticles with sizes similar to proteins, making them ideal for biomedical applications. Amphiphilic SCNPs result from the self-assembly in water of isolated synthetic polymeric chains through intrachain hydrophobic interactions, mimicking natural biomacromolecules and, specially, proteins (in size and when loaded with drugs, metal ions or fluorophores also in function). These ultrasmall, soft nanoparticles have various applications, including catalysis, sensing, and nanomedicine. Initial in vitro experiments with nonfunctionalized, amphiphilic SCNPs loaded with a photosensitizing Zn phthalocyanine with four nonperipheral isobutylthio substituents, ZnPc, showed promise for PDT. Herein, the preparation of improved, amphiphilic SCNPs containing ZnPc as highly efficient photosensitizer encapsulated within the nanoparticle and surrounded by anthracene units is disclosed. The amount of anthracene groups and ZnPc molecules within each single-chain nanoparticle controls the imaging and PDT properties of these nanocarriers. Critically, this work opens the way to improved PDT applications based on amphiphilic SCNPs as a first step toward ideal, long-term artificial photo-oxidases (APO)., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure-activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials., (© 2024 Wiley‐VCH GmbH.)

It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53 %, RES: 70.32 %) and high drug loading efficiencies (DOX: 51.54 %, RES: 36.93 %). The cumulative release efficiencies can reach 89.27 % for DOX and 80.05 % for RES in acidic medium within 96 h. The BCW/(DOX + RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOX + RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects., Competing Interests: Declaration of competing interest There are no conflicts of interest to be declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article reports a spectrofluorometric method for the determination of sunitinib (STB) drug based on molecularly imprinted nanofibers fabricated by the electrospinning method and modified by magnetic nanoparticles as sorbent. The characterization of magnetic molecularly imprinted nanofibers (MMINs) was carried out using X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM), which confirmed the successful synthesis of MMINs with well-distributed magnetite nanoparticles. Drug adsorption and desorption were optimized and important parameters such as sample pH, nanofiber mass, adsorption and desorption time, eluent solvent and sample volume were analyzed. The results demonstrated that the MMINs act as a selective sorbent for STB and can be readily collected through an external magnetic field. Methanol was used as the best eluent solvent for STB desorption from MNIN. A linear correlation was observed between the STB concentrations and fluorescence intensities in the range of 0.01-15.0 mg L -1 . The detection limit for this method was 0.002 mg L -1 . The relative standard deviation (RSD) of 2.6 % for 1.0 mg L -1 and 1.1 % for 10 mg L -1 of STB (n = 3) were obtained, which indicates that the developed method is precise in determining STB. Human serum and capsule analysis show the applicability of the proposed sensor for real samples., 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.)

Zr 4+ -doped polydopamine (Zr@PDA) nanozyme with phosphatase-like activity was synthesized by a one-pot hydrothermal method for the first time. Compared with previous representative phosphatase-mimicking nanozymes (i.e., CeO 2 NPs, ZrO 2 NPs and UiO-66), Zr@PDA not only exhibited higher dispersion stability in water, but also higher catalytical efficiency. K cat /K m of Zr@PDA is 35 and 12 times that of UiO-66 and ZrO 2 NPs, respectively, which would endow the Zr@PDA-based analytical methods with high sensitivity. As a demonstration, a novel colorimetric method based on Zr@PDA nanozyme was developed for sensitive detection of the drug fructose 1,6-diphosphate. The linear range is 1-15 μM with a detection limit as low as 0.38 μM., 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.)

β-Carboline bearing indole is one of the heterocyclic compounds that play a vital role in medicinal chemistry with various pharmacological effects such as anticancer, anti-acetylcholinesterase, anti-inflammation, antimalarial, antibacterial, anti-diabetic, and antioxidant. Over the last two decades, many studies on the synthesis and biological activity of indole β-carboline compounds have been conducted yet there is no appropriate data summary has been presented. Thus, the goal of this review was to highlight the synthesis pathway and bioactivity of substituted indole β-carboline reported from 2005 to date. In addition, this will encourage further investigation into the synthesis and evaluation of new indole β-carboline, in the hope of contributing to the development of potentially new medications for the treatment of various ailments.

Anticoagulation treatment for patients with high bleeding risk during hemodialysis is challenging. Contact between the dialysis membrane and the blood leads to protein adsorption and activation of the coagulation cascade reaction. Activated coagulation Factor X (FXa) plays a central role in thrombogenesis, but anticoagulant modification of the dialysis membrane is rarely targeted at FXa. In this study, we constructed an anticoagulant membrane using the polydopamine coating method to graft FXa inhibitors (apixaban and rivaroxaban) on the membrane surface. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the membranes. The apixaban- and rivaroxaban - modified membranes showed lower water contact angles, decreased albumin protein adsorption, and suppressed platelet adhesion and activation compared to the unmodified PES membranes. Moreover, the modified membranes prolonged the blood clotting times in both the intrinsic and extrinsic coagulation pathways and inhibited FXa generation and complement activation, which suggested that the modified membrane enhanced biocompatibility and antithrombotic properties through the inhibition of FXa. Targeting FXa to design antithrombotic HD membranes or other blood contact materials might have great application potential.

The transformation of monotherapy into multimodal combined targeted therapy to fully exploit synergistic efficacy is of increasing interest in tumor treatment. In this work, a novel nanodrug-carrying platform based on iron-based MOFs, which is loaded with doxorubicin hydrochloride (DOX), dihydroartemisinin (DHA), and glucose oxidase (GOx), and concurrently covalently linked to the photosensitizer 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) in polydopamine (PDA)-encapsulated MIL-101(Fe) (denoted as MIL-101(Fe)-DOX-DHA@TCPP/GOx@PDA, MDDTG@P), is successfully developed. Upon entering the tumor microenvironment, MDDTG@P catalyzes the hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals (·OH) and depletes glutathione (GSH); thus, exerting the role of chemodynamic therapy (CDT). The reduced Fe 2+ can also activate DHA, further expanding CDT and promoting tumor cell apoptosis. The introduced GOx will rapidly consume glucose and oxygen (O 2 ) in the tumor; while, replenishing H 2 O 2 for Fenton reaction, starving the cancer cells; and thus, realizing starvation and chemodynamic therapy. In addition, the covalent linkage of TCPP endows MDDTG@P with good photodynamic therapeutic (PDT) properties. Therefore, this study develops a nanocarrier platform for triple synergistic chemodynamic/photodynamic/starvation therapy, which has promising applications in the efficient treatment of tumors., (© 2024 Wiley‐VCH GmbH.)

A series of indole-1,4-disubstituted-1,2,3-triazole conjugates were synthesised by click chemistry. The haemolytic properties and cytoprotective activity of all the newly synthesised indole-triazole conjugates were tested in vitro . In addition, molecular docking was performed in silico for the selected conjugates to determine their antibacterial and antifungal properties. The results indicate that indole-triazole derivatives effectively protect human erythrocytes against free radical-induced haemolysis in a structure-dependent manner and that bis-indole-bis-triazole derivatives with alkyl linkers are excellent cytoprotective agents against oxidative haemolysis. The tested series of indole-1,4-disubstituted-1,2,3-triazole conjugates may have an affinity for the active sites of specific protein domains (PDB IDs: 2Q85 and 5V5Z) according to molecular docking studies.

In medical infections such as blood sepsis and in food quality control, fast and accurate bacteria analysis is required. Using magnetic nanoparticles (MNPs) for bacterial capture and concentration is very promising for rapid analysis. When MNPs are functionalized with the proper surface chemistry, they have the ability to bind to bacteria and aid in the removal and concentration of bacteria from a sample for further analysis. This study introduces a novel approach for bacterial concentration using polydopamine (pDA), a highly adhesive polymer often purported to create antibacterial and antibiofouling coatings on medical devices. Although pDA has been generally studied for its ability to coat surfaces and reduce biofilm growth, we have found that when coated on magnetic nanoclusters (MNCs), more specifically iron oxide nanoclusters, it effectively binds to and can remove from suspension some types of bacteria. This study investigated the binding of pDA-coated MNCs (pDA-MNCs) to various Gram-negative and Gram-positive bacteria, including Staphylococcus aureus , Staphylococcus epidermidis , Pseudomonas aeruginosa , and several E. coli strains. MNCs were successfully coated with pDA, and these functionalized MNCs bound a wide variety of bacterial strains. The efficiency of removing bacteria from a suspension can range from 0.99 for S. aureus to 0.01 for an E. coli strain. Such strong capture and differential capture have important applications in collecting bacteria from dilute samples found in medical diagnostics, food and water quality monitoring, and other industries.

In this study, a set of spiro[5,8-methanoquinazoline-2,3'-indoline]-2',4-dione derivatives 3a - p were synthesized starting from unsubstituted and N -methyl-substituted diendo - and diexo -2-aminonorbornene carboxamides, as well as various substituted isatins. The typical method involves a condensation reaction of alicyclic aminocarboxamide and isatin in the presence of a catalyst, using a solvent and an acceptable temperature. We developed a cost-effective and ecologically benign high-speed ball milling (HSBM), microwave irradiation (MW), and continuous flow (CF) technique to synthesize spiroquinazolinone molecule 3a . The structures of the synthesized compounds 3a - p were determined using 1D and 2D NMR spectroscopies. Furthermore, docking studies and absorption, distribution, metabolism, and toxicity (ADMET) predictions were used in this work. In agreement with the corresponding features found in the case of both the SARS-CoV-2 main protease (RCSB Protein Data Bank: 6LU7) and human mast cell tryptase (RCSB Protein Data Bank: 2ZA5) based on the estimated total energy and binding affinity, H bonds, and hydrophobicity in silico , compound 3d among our 3a - g , 3i - k , and 3m derivatives was found to be our top-rated compound.

Precise neuromodulation is critical for interrogating cellular communication and treating neurological diseases. Nanoscale transducers have emerged as effective interfaces to exert photothermal effects and modulate neural activities with a high spatiotemporal resolution. Ideal materials for this application should possess strong light absorption, high photothermal conversion efficiency, and great biocompatibility for clinical translation. Here, we show that the structurally designed 3D Au superparticles with a highly branched morphology can be promising candidates for nongenetic and remote neuromodulation. The structure-induced blackbody-like absorption endows Au superparticles with photothermal conversion efficiency over 90%, much higher than that of conventional Au nanorods. With the biocompatible polydopamine ligands, Au superparticles can be readily interfaced with primary mouse hippocampal neurons and other cells and can photostimulate or inhibit their activities in both cell networks or with a single-cell resolution. These findings highlight the importance of structural designs as powerful tools to promote the performance of plasmonic materials in neuromodulation and related research of neuroscience and neuroengineering.

This study investigates novel zinc and indium phthalocyanines with Schiff base and sulphur moieties, focusing on their potential for cancer therapy and antimicrobial applications. It explores the effectiveness of photochemical and sono-photochemical methods to enhance singlet oxygen production, which is crucial for photodynamic therapy. The synthesized complexes in this study demonstrated high singlet oxygen quantum yields, with D3 (ZnPc) and D4 (InPc) showing Φ ΔPDT values of 0.71 and 0.75, and Φ ΔSPDT values of 0.91 and 0.94, respectively. Furthermore, the evaluation for biological properties revealed that both D3 and D4 exhibit significant antidiabetic properties, DPPH radical scavenging activity, DNA cleavage, antimicrobial activity, biofilm inhibition, and microbial cell viability impacts, both with and without photodynamic therapy. Notably, D3 and D4 achieved antimicrobial cell viability inhibition rates of 84.67 ± 4.67% and 98.32 ± 5.96%, respectively, showcasing their effectiveness in photodynamic antimicrobial therapy. Overall, the study highlights the potential of these phthalocyanine complexes as advanced photosensitizers, with strong singlet oxygen generation and promising biological activities, paving the way for future therapeutic applications.

Tyrosinase is an enzyme crucial for the progression of melanogenesis. Immoderate production of melanin may be the cause of hyperpigmentation and darkening leading to skin diseases. Tyrosinase is the most researched target for suppressing melanogenesis since it catalyzes the rate-limiting stage of melanin production. Thiosemicarbazones have been reported to possess strong inhibition capability against tyrosinase. We have designed and synthesized eighteen N-tosyl substituted indole-based thiosemicarbazones as competitive tyrosinase inhibitors in the current work. All the compounds exhibited outstanding to good potency with half maximal inhibitory concentration in the range of 6.40 ± 0.21 µM to 61.84 ± 1.47 µM. The compound 5r displayed the top-tier inhibition amongst the entire series with IC 50  = 6.40 ± 0.21 µM. Compounds, 5q and 5r exhibited competitive inhibitions in concentration dependent manner with Ki = 3.42 ± 0.03 and 10.25 ± 0.08 µM respectively. The binding mode of 5r was evaluated through in silico molecular dynamics simulations and molecular docking, while ADME assessment studies predicted the drug-like characteristics of the derivatives. The newly synthesized derivatives may serve as a structural guide for designing and developing novel tyrosinase inhibitors., (© 2024. The Author(s).)

Background: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence., Methods: In this study, Gd 3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs' anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer., Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd 3+ ) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Liu et al.)

Coprisidins, a new class of indole alkaloids, feature a 1,4-naphthoquinone moiety attached to C-3 of 2-oxindole. Heterologous expression of a type II polyketide synthase-containing gene cluster resulted in the generation of three coprisidins. Gene disruption and isotope feeding studies suggested that the 2-oxindole moieties of coprisidins originate from a tetracyclic aromatic polyketide through oxidative rearrangements. This represents a novel biosynthetic route for the synthesis of indole rings in nature.

Sports doping remains a significant challenge in competitive sports. Given that urine analysis is the standard for detecting doping, developing rapid, sensitive, accurate, and high-throughput methods for stimulant detection in urine is crucial. Surface-enhanced Raman scattering (SERS) tag-based immunoassays have emerged as powerful analytical tools known for their high sensitivity and specificity, holding particular promise for stimulant detection in urine samples. However, both the Raman signals of typical SERS tags and sample matrices are within the Raman fingerprint region (<1800 cm -1 ), which could lead to spectrum overlap, potentially reducing detection accuracy and sensitivity. By recognizing this, we designed a competitive immunoassay that integrates two types of zero-background SERS tags and magnetic separation. These innovative SERS tags exhibit distinctive Raman peaks within the Raman-silent region (1800-2800 cm -1 ), effectively mitigating potential spectrum overlap with background sample signals. Moreover, magnetic separation not only enhances operational simplicity but also improves the system's anti-interference capability. Using clenbuterol (CL) and higenamine (HM) as model targets, the SERS-based competitive immunoassay demonstrated sensitive detection of individual CL or HM standards, with limits of detection (LODs) of 0.87 and 0.71 pg/mL, respectively. In multiplex mode, CL and HM can be simultaneously detected with LODs of 1.0 and 0.81 pg/mL, respectively. Furthermore, the recovery rates in urine samples ranged from 83 to 116% (relative standard deviation, RSD ≤ 6.4%) for CL and from 82 to 103% (RSD ≤ 5.1%) for HM, further confirming the reliability of the SERS-based immunoassay for practical applications.

Circulating cancer stem cells (CCSCs) are subpopulations of cancer cells with high tumorigenicity, chemoresistance, and metastatic potential, which are also major drivers of disease progression. Herein, to achieve the prediction of tumor diagnosis and progression in colorectal cancer (CRC), a new, automated, and portable lateral displacement patterned pump-free (LP) microfluidic chip (LP-chip) with the CoPt 3 nanozyme was established for CCSC capture and detection in peripheral blood and feces samples ex vivo. In this design, CoPt 3 @HA probes with functions of magnetic separation and colorimetric signal transduction by peroxidase-mimicking activity were applied for the capture of CCSCs and signal output in clinical samples. The generated colors of polydopamine (PDA) were quantifiable through the smartphone APP and visualizable by the naked eye in the test line (T line) and control line (C line) of the LP-chip. In the optimal experimental conditions, the CCSC concentration was sensitive to change in the range 0-10 5 cells mL -1 , with a detection limit of 3 cells mL -1 (S/N = 3). Preliminary studies of clinical samples suggest that the platform has the potential for prediction of colorectal cancer progression and poor prognosis. Overall, the LP-chip provides potential strategies for timely diagnosis, therapeutic monitoring, and recurrence prediction to improve home-based patient care.

This study investigates the biodistribution of a nano lipid carrier system (NLCs) containing the hydrophobic drug erlotinib (ERL-NLCs). The system was labelled with the fluorescent dye IR-780 for real-time dynamic imaging. ERL-NLCs were initially developed using the ultrasonication method with oleic acid and stearic acid. In vitro and ex vivo studies were performed to confirm the formation and penetration of NLCs within the intestine. Subsequently, the biological distribution of ERL-NLCs was monitored using a fluorescent dye through the IVIS® fluorescent optical imaging technique in whole live animals. Mice were orally administered blank IR 780 dye solution, ERL suspension, and IR 780 labelled NLCs. Fluorescence images were acquired at different time intervals up to 24 h and then total radiant efficiency was calculated through the region of interest (ROI) of the whole animal at each interval of time for all three groups. To validate the results obtained from in vivo imaging, various organs including lungs, heart, liver, both kidneys, stomach, and intestine were subsequently extracted and examined after 24 h. The ROI was found to be higher in the blank IR 780 dye solution, followed by the drug suspension and IR 780 labelled NLCs. These results confirm that the plain ERL suspension distributes across the body, and its encapsulation in NLCs facilitates passage through the lymphatic intestinal pathway, effectively avoiding first-pass metabolism. The remarkable results indicated that the NLCs formulation effectively circumvents first-pass metabolism by adopting the intestinal lymphatic pathway, thereby enhancing the oral bioavailability of the drug. This observed behaviour underscores the potential of NLCs in optimizing drug delivery and minimizing adverse effects associated with gastrointestinal and metabolic processes., 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.)

Toxoplasmosis, a zoonotic infection caused by Toxoplasma gondii ( T. gondii ), poses a significant risk to human health and public safety. Despite the availability of clinical treatments, none effectively mitigate the intestinal barrier damage, which is the primary defense against T. gondii invasion. This study introduced aldehyde groups into the indole scaffold of a peptide-like structure to investigate the protective effects of these indole aldehyde derivatives on the intestinal barrier in mice with acute T. gondii infection. This approach leveraged the propensity of peptides and aldehyde groups to form hydrogen bonds. We synthesized a range of indole derivatives using the Vilsmeier-Haack reaction and evaluated their intestinal barrier protective effects both in vitro and in vivo. Our findings revealed that indole derivatives A1 (1-Formyl-1 H -indole-3-acetonitrile), A3 (Indole-3-carboxaldehyde), A5 (2-Chloro-1 H -indole-3-carboxaldehyde), A8 (1-Methyl-indole-3-carboxaldehyde), and A9 (1-Methyl-2-phenyl-1 H -indole-3-carboxaldehyde) demonstrated a higher selectivity index compared to the positive control, spiramycin. These derivatives enhanced gastrointestinal motility, increased glutathione (GSH) levels in the small intestine, and reduced malondialdehyde (MDA) and nitric oxide (NO) levels in the small intestine tissue and diamine oxidase (DAO) and NO levels in the serum of infected mice. Notably, A3 exhibited comparable anti- T. gondii tachyzoites activity in the peritoneal cavity. Molecular docking studies indicated that the aldehyde group on the indole scaffold not only formed a hydrogen bond with NTPase-II but also interacted with TgCDPK1 through hydrogen bonding. Among the derivatives, A3 showed promising intestinal barrier protective effects in mice with acute T. gondii infection. This research suggests that indole derivatives could serve as a potential therapeutic strategy for intestinal diseases induced by T. gondii, offering a novel direction for treating intestinal barrier damage and providing valuable insights for the chemical modification of drugs targeting T. gondii . Furthermore, it contributes to the advancement of therapeutic approaches for toxoplasmosis.

Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5 ° C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Nicotinamide mononucleotide (NMN), a precursor of the coenzyme nicotinamide adenine dinucleotide (NAD+), has gained wide attention as an anti-aging agent, which plays a significant role in intracellular redox reactions. However, its effectiveness is limited by easy metabolism in the liver and subsequent excretion as nicotinamide, resulting in low bioavailability, particularly in the brain. Additionally, the blood-brain barrier (BBB) further hinders NMN supply to the brain, compromising its potential anti-aging effects. Herein, we developed a biocompatible polydopamine (PDA) platform to deliver NMN for boosting NAD+ levels in the brain for the first time. The lactoferrin (Lf) ligand was covalently attached to the PDA spheres to improve BBB transport efficiency. The resultant PDA-based system, referred to as PDA-Lf-NMN, not only exhibited superior BBB penetration ability but also improved the utilization rate of brain NMN in elevating NAD+ levels compared to NMN alone for both young (3 months) and old (21 months) mice. Moreover, after the old mice were treated with low-dose PDA-Lf-NMN (8 mg kg -1 day -1 ), they exhibited improved spatial cognition. Importantly, these nanomedicines did not induce any cellular necrosis or apoptosis. It provides a promising avenue for delivering NMN specifically to the brain, boosting NAD+ levels for promoting longevity and treating brain aging-related diseases.

A free-standing electrode based on carbon cloth-supported Fe-doped polydopamine-derived carbon (Fe/PDA-C/CC) was developed for the simultaneous detection of dopamine (DA) and uric acid (UA). First, dopamine was self-polymerized on the surface of the carbon cloth to obtain polydopamine coatings. Subsequently, Fe 3+ was introduced through the formation of a coordinate bond with the hydroxyl functional group in the polydopamine layer. After calcination, a flexible and free-standing electrode was obtained. The sensing performance and mechanism of the Fe/PDA-C/CC sensor was investigated and is discussed in detail herein. Experimental results demonstrated that Fe/PDA-C/CC could simultaneously detect DA and UA with a wide detection range of 0.5-300 μM and 0.5-400 μM with low detection limits of 0.041 μM and 0.012 μM, respectively. Meanwhile, Fe/PDA-C/CC possessed excellent anti-interference performance, repeatability, stability, and accuracy in real samples. Overall, this study provides a facile and effective approach for simultaneous detection of UA and DA.

Tuberculosis remains a leading cause of death from a single infection worldwide. Drug resistance to existing and even new antimycobacterials calls for research into novel targets and unexplored mechanisms of action. Recently we reported on the development of tight-binding inhibitors of Mycobacterium tuberculosis (Mtb) lipoamide dehydrogenase (Lpd), which selectively inhibit the bacterial but not the human enzyme based on a differential modality of inhibitor interaction with these targets. Here we report on the striking improvement in inhibitor residence time on the Mtb enzyme associated with scaffold progression from an indazole to 2-cyanoindole. Cryo-EM of Lpd with the bound 2-cyanoindole inhibitor 19 confirmed displacement of the buried water molecule deep in the binding channel with a cyano group. The ensuing hours-long improvement in on-target residence time is associated with enhanced antibacterial activity in axenic culture and in primary mouse macrophages. Resistance to 2-cyanoindole inhibitors involves mutations within the inhibitor binding site that have little effect on inhibitor affinity but change the modality of inhibitor-target interaction, resulting in fast dissociation from Lpd. These findings underscore that on-target residence time is a major determinant of antibacterial activity and in vivo efficacy., (© 2024 Wiley-VCH GmbH.)

Fibroblast growth factor receptor 1 (FGFR1) is emerging as a promising molecular target of lung cancer, and various FGFR1 inhibitors have exhibited significant therapeutic effects on lung cancer in preclinical research. Due to their low targeting ability or bioavailability, direct administration of these inhibitors may cause side effects. Herein, a hydrogelator, Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr-OH ( Nap-Y ), was rationally designed to coassemble with an FGFR1 inhibitor nintedanib ( Nin ) to form a peptide hydrogel Gel Y/Nin for localized administration and FGFR1-triggered release of Nin . Upon specific phosphorylation by FGFR1 overexpressed on lung cancer cells, Nap-Y in Gel Y/Nin is converted to the hydrophilic product Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr(H 2 PO 3 )-OH ( Nap-Yp ), leading to dehydrogelation of the gel and subsequent Nin release. In vitro experiments demonstrate that the release of Nin in a sustained manner from Gel Y/Nin significantly suppresses the survival, migration, and invasion of A549 cells by inhibiting FGFR1 expression and its phosphorylation function on downstream signaling molecules. Nude mouse studies show that Gel Y/Nin exhibits enhanced therapeutic efficacy on lung tumor than free Nin . We anticipate that Gel Y/Nin will be utilized for lung cancer treatment in clinical settings in the near future.

Tautomers are one of the many types of isomers, and differences in tautomeric structures confer altered chemical and biological properties. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) ex vivo metabolomics, we investigate, in whole blood, the divergent metabolism of enol and keto forms of indole-3-pyruvate (IPyA), a tautomeric product of aromatic amino acid metabolism. Two new compounds resulting from IPyA metabolism were discovered, 3-(1 H -indol-3-yl)-2,3-dioxopropanoic acid or "indole-3-oxopyruvic acid" and glutathionyl-indole pyruvate (GSHIPyA), which were characterized via ultraviolet photodissociation (UVPD) and higher-energy collisional dissociation (HCD). Computational calculations support the hypothesis that GSHIPyA forms specifically through the enol form of IPyA. GSHIPyA is also hypothesized to be tautomeric, and a hydrogen-deuterium exchange-high-resolution tandem mass spectrometry (HDX-HRMS/MS) approach is developed to prove the presence of an enol and keto tautomer. HDX of GSHIPyA labels the keto form with an additional deuterium, relative to the enol form. HRMS/MS of the labeled isomers is employed to leverage the relationship of resolving power scaling inversely with the square root of m / z , for Orbitrap mass analyzers. HRMS/MS yields a smaller-molecular-weight deuterated tautomeric product ion, reducing the analyte ion m / z and thus lowering the resolving power necessary to separate the deuterated keto tautomer product ion from the [13]C product ion.

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases., (© 2024. The Author(s).)

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy., (© 2024. The Author(s).)

Excessive bleeding presents a grave risk to life, especially in scenarios involving deep wounds such as those inflicted by gunshots and accidental stabs. Despite advancements in wound care management, existing commercial hemostatic agents have limitations, necessitating the development of enhanced solutions. In this study, we developed cryogels using agarose and polydopamine microspheres as a hemostatic dressing to effectively manage profuse bleeding. The resulting cryogels demonstrated impressive attributes, such as high absorption capacity (>4000%), shape recovery ability, antioxidant properties, and excellent biocompatibility in mammalian cell lines. Particularly noteworthy was the rapid blood clotting observed in vitro, with the agarose/PDA cryogels achieving complete clotting within just 90 s. Subsequent validation in the rat trauma model further underscored their hemostatic efficacy, with clotting times of 40 and 53 s recorded in tail amputation and liver puncture models, respectively. The porous structure and hydrophilicity of the cryogels facilitated superior blood absorption and retention, while the amine groups of polydopamine played a pivotal role in enhancing blood clotting activity. This study represents a significant step forward in utilizing agarose/polydopamine cryogels as advanced materials for hemostatic wound dressings, promising an impactful contribution to wound therapy.

Nonspecific reactive chemicals often interfere with the interpretation of high-throughput assay results because of their promiscuity and/or cytotoxicity. Using a high-throughput assay to identify such compounds is necessary to efficiently rule out potential assay artifacts. The MSTI, ( E )-2-(4-mercaptostyryl)-1,3,3-trimethyl-3 H -indol-1-ium, assay uses a thiol-containing fluorescent probe to screen for electrophile reactivity and could potentially be used to determine nonspecific reactive compounds. The Tox21 10K compound library was previously screened against a panel of ∼80 cell-based and biochemical assays, including the biochemical MSTI assay. In this study, we compared the MSTI assay activity of the Tox21 10K compounds with their promiscuity and cytotoxicity as reflected by their activities across the Tox21 assay panel to determine: (1) if this assay is predictive of a compound's promiscuity and cytotoxicity and (2) what chemical features create inconsistent results between the MSTI assay activity and promiscuity/cytotoxicity (false negatives and false positives). We found that the MSTI assay can predict a chemical's promiscuity/cytotoxicity with a 0.55 sensitivity and 0.97 specificity. Out of 3,407 unique compounds evaluated, we identified 92 false positive and 227 false negative results. Several structural features such as carboxamides and alkyl halides were found to be apparent in 53% ( p = 2.4 × 10 -07 ) and 19% ( p = 4.3 × 10 -06 ) of the false positives and negatives, respectively. The results of this analysis will help identify the potential challenges of this high-throughput assay and allow researchers to identify if a compound will be cytotoxic or promiscuous in an efficient manner.

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

We describe the design, synthesis and structure-activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1 H -indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT 1A ) and dopamine (D 2 ) receptors and the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) transporters as multi-target directed ligands for the treatment of depression. All of the tested compounds demonstrated good affinity for the serotonin transporter (SERT). Among them, compounds 11 and 4 emerged as the lead candidates because of their promising pharmacological profile based on in vitro studies. Compound 11 displayed a high affinity for the 5-HT 1A ( K i = 128.0 nM) and D 2 ( K i = 51.0 nM) receptors, and the SERT ( K i = 9.2 nM) and DAT ( K i = 288.0 nM) transporters, whereas compound 4 exhibited the most desirable binding profile to SERT/NET/DAT among the series: K i = 47.0 nM/167.0 nM/43% inhibition at 1 µM. These results suggest that compounds 4 and 11 represent templates for the future development of multi-target antidepressant drugs.

Indolocarbazoles are natural products with a broad spectrum of bioactivity. A distinct feature of indolocarbazole biosynthesis is the modification of the indole and maleimide rings by regioselective tailoring enzymes. Here, we study a new indolocarbazole variant, which is encoded by the acfXODCP genes from Streptomyces venezuelae ATCC 10712. We characterise the pathway by expressing the acfXODCP genes in Streptomyces coelicolor, which led to the production of a C-5/C-5'-dihydroxylated indolocarbazole, which we assign as arcyriaflavin F. We also show that a flavin-dependent monooxygenase AcfX catalyses the C-5/C-5' dihydroxylation of the unsubstituted arcyriaflavin A into arcyriaflavin F. Interestingly, AcfX shares homology to EspX from erdasporine A biosynthesis, which instead catalyses a single C-6 indolocarbazole hydroxylation. In summary, we report a new indolocarbazole biosynthetic pathway and a regioselective C-5 indole ring tailoring enzyme AcfX., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

Azaindole scaffold is a privileged structure in medicinal chemistry and some derivatives have demonstrated to be potential anticancer drugs. Herein, a set of novel azaindoles, comprising the four regioisomers, bearing a morpholine (azaindoles 3 a-d) and N-methyl-N-benzylamine (azaindoles 4 a-d) groups were prepared. Among these compounds, azaindoles 4 exhibited higher cytotoxicity against the ovarian cancer cell line A2780 and normal dermal fibroblasts compared to azaindoles 3. Furthermore, azaindoles 4 b and 4 c promoted a delay in the cell cycle of the cancer cell line, inspiring an investigation into the intracellular localization of these derivatives., (© 2024 Wiley-VCH GmbH.)

Heterogeneous catalyst-mediated sulfate radical-based advanced oxidation processes (SR-AOPs) showed excellent performance during antibiotics degradation. Spinel was a promising catalyst for SR-AOPs, but the secondary contamination due to metal ions leaching needed to be addressed. And the destruction of catalyst structure could lead to the reduction of catalytic activity and the difficulty of recovery. Thus, a novel nitrogen-doped carbon (NC)-supported CoFe 2 O 4 (CoFe 2 O 4 @NC) was synthesized as the activator of PMS for sulfadiazine (SDZ) degradation under low Co leaching conditions. The consequences indicated that the CoFe 2 O 4 @NC/PMS system exhibited higher PMS decomposition efficiency and reaction stoichiometry efficiency than the bare CoFe 2 O 4 /PMS systems (CoFe 2 O 4 -180 and CoFe 2 O 4 -800), which in turn demonstrated a better SDZ removal performance. Under the condition of CoFe 2 O 4 @NC dosage 0.1 g/L, PMS concentration 0.5 mM, solution pH 6.8 and temperature 25°C, SDZ (20 mg/L) was almost completely degraded within 60 min. XPS analysis showed that the NC not only protected and stabilized CoFe 2 O 4 , but also provided additional active sites for PMS activation. During SDZ degradation, SO 4 •- , HO • , • O 2 - and 1 O 2 were involved in the reaction, among which SO 4 • and HO • made the main contribution. Meanwhile, CoFe 2 O 4 @NC could be recovered by magnetic separation, and showed great stability (Co leaching 0.852 mg/L) and reusability. In the fifth cycle experiment, 85.02 % SDZ degradation was obtained. Based on the detected intermediates (12 intermediates were identified) and DFT calculations, possible degradation pathways for SDZ in CoFe 2 O 4 @NC/PMS were proposed. The condensed dual descriptor indicated that the N7, N11, and C15 atoms on SDZ molecule were the main sites of electrophilic attack, which was consistent with the detected intermediates. The degradation of SDZ involved hydroxylation of NH 2 , cleavage of S-N and extrusion of SO 2 . This study explored the improvements made in NC support material to catalytic performance and resistance to dissolution of spinel, providing new insights for subsequent researches., 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 Inc. All rights reserved.)

The detrimental environmental effects of surfactant-like contaminants (SLCs) with distinctive amphiphilic structures have garnered significant attention, particularly since perfluorooctanesulfonate was classified as a persistent organic pollutant. Despite the numerous absorbents developed for SLCs removal, the underlying interaction mechanisms remain speculative and lack experimental validation. To address this research gap, we elucidate the mechanistic insights into the selective removal of SLCs using mesoporous polydopamine nanospheres (MPDA) fabricated via a novel soft-template method. We employed low-field nuclear magnetic resonance to quantitatively characterize the hydrophilicity of the absorbents using water molecules as probes. The results demonstrated that MPDA with uniform mesopores exhibited a remarkable threefold enhancement in SLCs' adsorption capacity compared to conventional polydopamine particles via intraparticle diffusion. We further demonstrated the dominant effects of electrostatic and hydrophobic interactions on the selective removal of SLCs with MPDA by regulating the isoelectric pH value and performing a comparative analysis. The mechanism-inspired SLC-removal strategy achieved an average removal rate of 76.3% from highly contaminated wastewater. Our findings offer new avenues for applying MPDA as an efficient adsorbent and provide innovative and mechanistic insights for targeted SLC removal in complex wastewater matrices.

Nitrite (NO 2 - ) widely exists in our daily diet, and its excessive consumption can lead to detrimental effects on the human central nervous system and an elevated risk of cancer. The fluorescence probe method for the determination of nitrite has developed rapidly due to its simplicity, rapidity and sensitivity. Despite establishing various nitrite sensing platforms to ensure the safety of foods and drinking water, the simultaneous achievement of rapid, specific, affordable, visualizing, and on-site nitrite detection remains challenging. Here, we designed a novel fluorescent probe by using Rhodamine 800 as the fluorescent skeleton and 5-aminoindole as the specific reaction group to solve this problem. The probe shows a maximal fluorescence emission at 602 nm, thereby avoiding background emission interference when applied to food samples. Moreover, this unique probe exhibited excellent sensing capabilities for detecting nitrite. These included: a rapid response time within 3 min, a noticeable color change that the naked eye can observe, a low detection limit of 13.8 nM, and a remarkable selectivity and specificity to nitrite. Besides that, the probe can detect nitrite quantitatively in barreled drinking water, ham sausage, and pickles samples, with good recoveries ranging from 89.0 % to 105.8 %. More importantly, based on the probe fixation and signal processing technology, a portable and smart sensing platform was fabricated and made convenient and rapid analysis the content of NO 2 - in real samples possible. The results obtained in this work provide a new strategy for the design of high-performance nitrite probes and feasible technology for portable, rapid and visual detection of nitrite, and this probe holds the potential as a practical tool for alleviating concern regarding nitrite levels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ran Yang, Tengyu Yang, Yuanqiang Sun, Zhaohui Li and Lingbo Qu have submitted a patent application to the China patent office., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from β-cyclodextrin (β-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 μg mL -1 with a limit of detection at 0.027 μg mL -1 and a limit of quantification at 0.089 μg mL -1 . Notably, the proposed β-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host-guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring., 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 © 2023. Published by Elsevier Ltd.)