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Synthetic cannabinoids (SCs) have emerged as one of the most severely abused categories of new psychoactive substances (NPS), exacerbating the global drug problem and posing significant threats to public health. Presently, a class of new amide-type SCs featuring an indazole or indole core has been identified in numerous cases of illegal drug use, but there is still a lack of comprehensive analysis methods of SC detection. Herein, monoclonal antibodies (mAbs) 2E4 and AE6 targeting 36 indole-type and indazole-type SCs and their metabolites with IC 50 ranging from 0.14 to 85.28 ng/mL were prepared and the molecular mechanism of antibody recognition was elaborated. We established the indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and gold immunochromatography assay (GICA) based on mAbs 2E4 and AE6 to detect indazole-type and indole-type SCs in urine and hair samples. Under optimal conditions, the proposed method detected ADB-BUTINACA (an indazole-type SC) with limits of detection (LODs) of 0.11 ng/mL for urine and 0.024 ng/mg for hair by ic-ELISA, and 1.02 ng/mL for urine and 0.046 ng/mg for hair by GICA; the LODs of 4F-MDMB-BUTICA (an indole-type SC) detection was 0.036 ng/mL for urine and 0.012 ng/mg for hair by ic-ELISA, and 0.54 ng/mL for urine and 0.03 ng/mg for hair by GICA. Collectively, our study provides a comprehensive foundation for the rapid screening and quantitation of SC derivatives in biological samples.

Infections and thrombosis remain unsolved problems for implanted cardiovascular devices, such as left ventricular assist devices. Hence, the development of surfaces with improved blood compatibility and antimicrobial properties is imperative to reduce complications after artificial heart implantation. In this work, we report a novel approach to fabricate multifunctional surfaces for left ventricular transplanted ventricular assist devices (LVADs) by immobilizing nitric oxide (NO) generation catalysts and heparin and reducing silver nanoparticles in situ. The general view, structure, and chemical compositions of the pure/modified surfaces were characterized using digital imaging, scanning electron microscope (SEM), atomic force microscope (AFM), water contact angle (WCA), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma (ICP). All of the results demonstrated that the AgNPs and heparin were successfully immobilized on the surface. The Cu ions and NO release experimental results showed that the immobilized copper ions could catalyze the production of NO from S -nitrosothiols within the biological system. Meanwhile, due to the synergistic anticoagulant effect of NO and surface-immobilized heparin, the fabricated modified surfaces exhibited antiplatelet adhesion activities and good hemocompatibility. Finally, the antimicrobial activity of the samples was evaluated by Escherichia coli and Staphylococcus aureus , and cytocompatibility was measured using human umbilical vein endothelial cells (HUVECs). The results demonstrated that silver nanoparticles (AgNPs) immobilized by surface reduction reaction did not cause any significant inhibition of cell proliferation while providing stable and effective antimicrobial properties. We envision that this simple surface modification strategy with bifunctional activities of antimicrobial and anticoagulant will find widespread use in clinically used indwelling left ventricular assist devices.

Biofilm formation on medical implants such as catheters is a major issue which needs to be addressed as it leads to severe health care associated infections. This study explored the design and synthesis of a polydopamine-lipopeptide based antimicrobial coating. The coating was used to modify the surface of Ultrathane Catheters. The lipopeptide SL1.15 with an N -terminal cysteine was covalently conjugated to the polydopamine modified catheters via a Michael addition reaction between the thiol moiety in the peptide and the aromatic ring in the polydopamine layer. The immobilization of the peptide on the polydopamine coated catheters was confirmed using water contact angle, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy (SEM). The antimicrobial activity of the coated catheters investigated using drug resistant and clinical strains of Gram-positive (MRSA and S. aureus ) and Gram-negative ( E. coli , A. baumannii , and P. aeruginosa ) bacteria revealed that lipopeptide immobilization inhibited >90% bacterial adhesion to the catheter surface. Additionally, biofilm assays against MRSA and E. coli revealed that the lipopeptide immobilized catheters inhibited >85% bacterial growth after 1 week incubation. Finally, the cytotoxicity profile of the catheters using the human dermal fibroblast, and the human embryonic kidney cell lines demonstrated that the polydopamine-lipopeptide coating was not toxic after 72 h incubation.

Antimicrobial resistance remains an enduring global health issue, manifested when microorganisms, such as bacteria, lack responsiveness to antimicrobial treatments. Photodynamic inactivation (PDI) of microorganisms arises as a noninvasive, nontoxic, and repeatable alternative for the inactivation of a broad range of pathogens. So, this study reports the synthesis, structural characterization, and photophysical properties of a new tetra-β-substituted pyridinium-pyrazolyl zinc(II) phthalocyanine (ZnPc 1a ) that was compared with two previously described pyridinium-pyrazolyl ZnPcs 2a and 3a . The PDI efficacy of these three ZnPcs ( 1a - 3a ) against a drug-resistant Gram-positive bacterium (as Staphylococcus aureus ) and a Gram-negative bacterium (as Escherichia coli ) is also reported. The PDI efficacy toward these bacteria was examined with ZnPcs 1a - 3a in the 5.0-10.0 μM range using a white light source with an irradiance of 150 mW/cm 2 . All ZnPcs displayed a significant PDI activity against S. aureus , with reductions superior to 3 Log CFU/mL. Increasing the treatment time, the E. coli was inactivated until the detection limit of the method (>6.3 Log CFU/mL) using the quaternized ZnPcs 1a - 3a (10.0 μM, 120 min) being the inactivation time was reduced when added the KI for ZnPcs 1a and 3a . These findings demonstrate the effective PDI performance of pyridinium-pyrazolyl group-bearing PSs, indicating their potential use as a versatile antimicrobial agent for managing infections induced by Gram-negative and Gram-positive bacteria.

Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology., (© 2024 Wiley-VCH GmbH.)

The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor integral to various physiological and pathological processes. Among its diverse ligands, indole-based compounds have garnered attention due to their significant biological activity and potential therapeutic applications. This study explores the activation of AhR by structurally diverse halogenated indoles. We evaluated the transcriptional activity of AhR and cell viability in the human LS174T-AhR-luc reporter cell line. Among the tested compounds, 4-FI, 7-FI, 6-BrI, 7-BrI, 6-Cl-2-ox, 5-Br-2-ox, and 6-Br-2-ox activated AhR in a concentration-dependent manner, displaying high efficacy and potency. Molecular docking analysis revealed moderate binding affinities of these compounds to the PAS-B domain of AhR, corroborated by competitive radioligand binding assays. Functional assays showed that halogenated indoles induce the formation of AhR-ARNT heterodimer and enhance the binding of the AhR to the CYP1A1 promoter. Additionally, 4-FI and 7-FI exhibited anti-inflammatory properties in Caco-2 cell models, highlighting their potential for therapeutic applications. This study underscores the significance of the type and position of halogen moiety in indole scaffold, suggesting their potential as candidates for developing therapeutics drugs to treat conditions such as inflammatory bowel disease via AhR activation., 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.)

In this study, a porous polydopamine (PDA) nanoparticle-decorated β-glucan microcapsules (GMs) nanoplatform (PDA/GMs) were developed with macrophage-targeted biomimetic features and a carriers-within-carriers structure. Indocyanine green (ICG) and catalase (CAT) were subsequently co-encapsulated within the PDA/GMs to create a multifunctional nanotherapeutic agent, termed CIPGs. Furthermore, CIPGs and sinomenine (SIN) were co-loaded within a thermo-sensitive hydrogel to design an injectable delivery system, termed CIPG/SH, with potential for multi-modal therapy of rheumatoid arthritis (RA). Photothermal studies indicated that the CIPGs hold excellent photothermal conversion ability and thermal stability, as they combined the photothermal performance of both PDA and ICG. Meanwhile, the CIPGs displayed favorable oxygen self-supplying and photodynamic performance. The CIPGs showed near-infrared (NIR)-induced phototoxicity, effectively inhibiting macrophage proliferation and displaying remarkable antibacterial activity. In vitro drug release from the prepared CIPG/SH showed a controlled release pattern. Animal experiments conducted on an RA mice model confirmed that the formulated CIPG/SH exhibited significant therapeutic effects. By integrating the biological advantages, photothermal/photodynamic performance of the CIPGs, and controlled drug release performance of the thermo-sensitive hydrogels in a single delivery system, the prepared injectable CIPG/SH represents a novel versatile delivery system with great potential for multi-modal combination targeting therapy in RA., 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.)

Stimuli-responsive nanoplatforms have been popular in controlled drug delivery research because of their ability to differentiate the tumor microenvironment from the normal tissue environment in a spatiotemporally controllable manner. The synergistic therapeutic approach of combining cancer chemotherapy with photothermal tumor ablation has improved the therapeutic efficacy of cancer therapeutics. In this study, a UiO-66 metal organic framework (MOF)-based system loaded with doxorubicin (DOX), surface decorated with the photothermal agents indocyanine green (ICG) and polydopamine (PDA), and conjugated with transferrin (TF) was successfully designed to operate as a responsive system to pH changes, featuring photothermal capabilities and target specificity for the purpose of treating breast cancer. The synthesized nanoplatform benefits from its uniform size, excellent DOX encapsulation efficiency (91.66 %), and efficient pH/NIR-mediated controlled release of the drug. In vitro photothermal studies indicate excellent photothermal stability of the formulation even after 6 on-off cycles of NIR irradiation. The in vitro cytotoxicity assessment using an NIR laser (808 nm) revealed that the DOX-loaded functionalized UiO-66 nanocarriers had outstanding inhibitory effects on 4T1 cells because of synergistic chemo-photo therapies, with no substantial toxicity by the carriers. In addition, cellular uptake evaluations revealed that UiO-DOX-ICG@PDA-TF could specifically target 4T1 cells on the basis of receptor-mediated internalization of transferrin receptors. Additionally, in vivo toxicity studies in Wistar rats indicated no signs of significant toxicity. The UiO-based nanoformulations effectively inhibited and destroyed cancer cells under 808 nm laser irradiation because of their minimal toxicity, strong biocompatibility, and outstanding synergistic chemo/photothermal/photodynamic treatment., 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.)

Characterizing the metabolic profiles of synthetic cannabinoids (SCs), a type of new psychoactive substances, is of particular importance for forensic detection and analysis. Although the metabolism of individual SCs derived from 1-amino-3,3-dimethyl-1-oxobutan-2-yl (ADB-SCs) has been reported, their metabolites also undergo a continuous change and combination of their tail and core regions. Therefore, elucidating the metabolic characteristics and effects of these structures is essential to enhance our understanding. In this study, the human liver microsome was used as the model for studying the in vitro phase I metabolism of 12 ADB-SCs, and the metabolites obtained were analyzed using ultra-high performance liquid chromatography-tandem four-level rod-electrostatic field orbital ion trap mass spectrometry to determine type, structure, and relative contents. The results indicated that hydroxylation and N-dealkylation were the major metabolic pathways in 12 ADB-SCs. The effects of the core and tail on the metabolism of these ADB-SCs were studied using theoretical calculations. For N-dealkylation metabolism, the strong electron-withdrawing conjugative effect of the -N= moiety in the pyrazole ring, steric hindrance of the tail, and electronic effect of substituents on the tail significantly affected metabolism. Further, it changed the relative contents of N-dealkylation metabolites. For hydroxylation, the reaction types were inconsistent at different parts. For instance, the phenyl group of the core is electrophilic, and its electron cloud density determines whether the phenyl group can be hydroxylated at the specific metabolic sites. Meanwhile, hydroxylation of the neopentyl moiety of the linked group involves the oxidation of aliphatic C-H bonds, whereas amide-hydroxylamine tautomerism affects hydroxylation metabolism. When the alkyl chain in the tail contains functional groups (such as -F and >CC<), oxidative defluorination or dihydrodiol metabolites are produced. Taken together, we systematically determined d the effect of functional groups in the core and tail of ADB-SCs on their metabolism, validating confirmed the feasibility of ADB-SC metabolism prediction based on their structural characteristics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xuan Luo reports equipment, drugs, or supplies and travel were provided by Science and Technology Department of Guangxi Zhuang Autonomous Region. 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 B.V. All rights reserved.)

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval This study was carried out in compliance with the recommendations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). The protocol (IAEC/21/05) was approved by the Institute of Microbial Technology’s Institutional Animal Ethics Committee in Chandigarh, India. We have complied with all relevant ethical regulations for animal use. We have used female, BALB/c mice of 5–7 weeks in our experiments. Randomization and blinding were not regarded as necessary for infection animal models. During the histopathology investigation, the observer was unaware of the control and treatment groups., (© 2024. The Author(s).)

It is crucial to precisely strike the bacterially infected area and avoid damaging healthy tissue in bacterial infection treatment. Herein, we report an acidity-triggered aggregation antibacterial nanoplatform based on biodegradable mesoporous organic silica nanoparticles (MON NPs). The surface of MON NPs modified with polydopamine (PDA) encapsulated ciprofloxacin (CIP) and methylene blue (MB) and was then further grafted with glycol chitosan to obtain MB/CIP@MON-PDA-GCS NPs (MCMPG NPs). In the bacterial infection environment with acidic characteristics, glycol chitosan (GCS) becomes positively charged. Consequently, the positively charged acidity-triggered GCS enables MCMPG NPs to accumulate on the negatively charged bacterial surfaces in the infected area and not in healthy tissue. The targeted method allows for the precise release of CIP and MB, ensuring the spatial accuracy of photodynamic therapy (PDT) and photothermal therapy (PTT) for effective bacteria-specific treatment.

Biocatalytic membranes have great potential in various industrial sectors, with the immobilization of enzymes being a crucial stage. Immobilizing enzymes through covalent bonds is a complex and time-consuming process for large-scale applications. Polydopamine (PDA) offers a more sustainable and eco-friendly alternative for enzyme immobilization. Therefore, surface modification with polydopamine as mussel-inspired antifouling coatings has increased resistance to fouling. In this study, α-amylase enzyme was covalently bound to a bioactive PDA-coated polyethersulfone (PES) membrane surface using cyanuric chloride as a linker. The optimal activity of α-amylase enzyme immobilized on PES/PDA membrane was obtained at temperature and pH of 55°C and 6.5, respectively. The immobilized enzyme can be reused up to five reaction cycles with 55 % retention of initial activity. Besides, it maintained 60 % of its activity after being stored for five weeks at 4°C. Additionally, the immobilized enzyme demonstrated increased Michaelis constant and maximum velocity values during starch hydrolysis. The results of the biofouling experiment of various membranes in a dead-end cell demonstrated that the PES membrane's water flux increased from 6722.7 Lmh to 7560.2 Lmh after PDA modification. Although α-amylase immobilization reduced the flux to 7458.5 Lmh due to enhanced hydrophilicity, compared to unmodified membrane. The findings of this study demonstrated that the membrane produced through co-deposition exhibited superior hydrophilicity, enhanced coating stability, and strong antifouling properties, positioning it as a promising candidate for industrial applications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Asghar Taheri-Kafrani reports financial support was provided by University of Isfahan. 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 B.V. All rights reserved.)

Introduction: The photo-activated thermo/gas antimicrobial nanocomposite hydrogel, Gel/PDA@BNN6, is composed of the nitric oxide (NO) carrier N, N'-di-sec-butyl-N, N'-dinitroso-p-phenylenediamine (BNN6), photothermal (PTT) material polydopamine nanoparticles (PDA NPs), and methacrylate gelatin (GelMA). This hydrogel can release NO gas in a stable and controlled manner, generating a localized photothermal effect when exposed to near-infrared laser light. This dual action promotes the healing of full-thickness skin wounds that are infected., Methods: Gel/PDA@BNN6 was developed, and both in vitro and in vivo experiments were carried out to evaluate its structure, physicochemical properties, antibacterial effects, effectiveness in promoting infected wound healing, and biocompatibility., Results: Gel/PDA@BNN6 was successfully synthesized, exhibiting a porous three-dimensional lattice structure and excellent mechanical properties. It demonstrated highly efficient photothermal conversion, controllable nitric oxide delivery, strong bactericidal effects, and minimal cytotoxicity in vitro. In vivo, Gel/PDA@BNN6, when used with NIR therapy, showed significant anti-inflammatory effects, promoted collagen deposition, and stimulated vascular neoangiogenesis, which accelerated wound closure. Additionally, it displayed superior biocompatibility., Discussion: Gel/PDA@BNN6 has shown an explicit curative effect for infected wound healing, suggesting it has a good chance of being an antimicrobial dressing in the future., Competing Interests: The authors declare no conflict of interest., (© 2024 Yang et al.)

In recent years, mussel-inspired polydopamine (PDA)-based materials have attracted significant attention in the field of open-tubular capillary electrochromatography (OT-CEC) owing to their diverse and appealing properties. However, previously established functionalized PDA coating-based CEC stationary phases predominantly relied on the latent reactivity of PDA with amine/thiol-containing molecules, limiting the types of applicable modifiers and requiring time-consuming reaction processes. Herein, we presented a versatile and efficient method for the facile and rapid fabrication of diverse functionalized PDA coatings as OT-CEC stationary phases through a Zr(IV) coordination-mediated post-modification strategy. Different kinds of modifiers, including octadecylamine (ODA), lauric acid (LA), and perfluorooctanoic acid (PFOA), were rapidly and robustly grafted onto the PDA coating, verified through multiple characterization techniques. The influences of preparation parameters on the grafting efficiency of the functionalized PDA coating were systematically investigated. Utilizing the Zr(IV)-mediated ODA-, LA- and PFOA-functionalized PDA-based OT-CEC columns, we achieved high-efficiency baseline separation of a series of neutral analytes with excellent repeatability, good stability, and long lifetime. Given the strong universality of the Zr(IV) coordination-mediated post-modification approach, our study provides an effective pathway for advancing the development of a wider range of functional PDA-based chromatographic stationary phases., 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.)

A highly sensitive and selective label-free impedimetric immunosensor based on AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite modified on the surface of a screen-printed electrode (SPE) was designed for the detection of interleukin-6 (IL-6). The distribution of NiCo 2 S 4 nanoparticles on MoS 2 nanosheets was able to prevent them from agglomerating. The polydopamine (pDA) layer was coated on the surface of NiCo 2 S 4 @MoS 2 nanosheets by self-polymerization, which improved the stability and biocompatibility of the nanomaterial. The excellent reduction ability of pDA promoted the synthesis of gold nanoparticles (AuNPs), which increased the amount of antibody adsorption and the conductivity of the material. Finally, the antibody (Ab) of IL-6 was immobilized on the surface of AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite. Electrochemical impedance spectroscopy (EIS) was used to detect the change of impedance before and after the immune response between Ab and IL-6 antigen (IL-6). Under the optimal experimental conditions, the relative change in impedance and the logarithmic concentration of IL-6 showed a good linear relationship in the range 1.00 to 1.00 × 10 6  pg/mL, with a low detection limit of 0.97 pg/mL. In addition, the proposed immunosensor performed with good reproducibility, stability, and specificity. It was successfully applied to the determination of IL-6 in patient's serum samples of head and neck carcinoma with recoveries of 98.40% to 106.5%. To sum up, the proposed label-free impedimetric immunosensor was successfully constructed for IL-6 detection in real samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration., (© 2024. The Author(s).)

A PHD (prolyl hydroxylase) inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), is a drug that can artificially promote tissue regeneration by enhancing metabolic activity through the upregulation of hypoxia inducible factor 1 subunit alpha (Hif-1α) under normoxic conditions. This study presents a novel design methodology for a drug delivery system to maximize the regenerative effect of 1,4-DPCA. Specifically, by encapsulating 1,4-DPCA in polydopamine (PDA) that generates reactive oxygen species (ROS), the combined effects of Hif-1α upregulation and the induction of cellular antioxidant defense mechanisms by localized ROS can significantly enhance tissue regeneration. The study confirmed that each material (PDA and 1,4-DPCA) triggers a positive synergistic effect on the regenerative mechanisms. As a result, the use of a PDA drug delivery system loaded with 1,4-DPCA showed approximately six times greater bone regeneration compared to the control (no treatment) in a mouse calvarial defect model.

Self-assembly has proven to be one of the effective methods for the formation of nanoscale therapeutics without the need to use nanodelivery systems. Such minimal models of supramolecular systems formed from amphiphilic photosensitizers (PS) have recently emerged as a new class of photoactive systems, providing unique and in some cases superior activities. Although the mechanism of photogenerated reactive oxygen species (ROS) in such systems is studied and to a certain extent understood, there are very limited studies investigating the influence of intricate environmental factors, including those occurring in the cellular environment, on the self-assembly and thus the activity of the system. Understanding the optimal conditions for the formation of active PS aggregates is an important area of research in the field of photodynamic therapy (PDT), as it is directly linked to the optimal treatment dose. In this study, we describe the synthesis, self-assembly properties, photophysical characterization, and photobiological efficacy of structurally closely related low-symmetry phthalocyanine derivatives. Studying the decay behavior of the PS fluorescence lifetime in the presence of molecular crowders and different bacterial strains, we found that certain derivatives exhibited adaptive behavior and change in activity, while others demonstrated non-adaptive characteristics., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The development of durable photosensitizers is pivotal for advancing phototherapeutic applications in biomedicine. Here, we introduce a core-shell azobenzene-spiropyran structure on gold nanoparticles, engineered to enhance singlet oxygen generation. These nano-photosensitizers exhibit increased structural stability and thermal resistance, as demonstrated by slowed O-N-C bond recombination dynamics via in-situ Raman spectroscopy. Notably, the in-situ formation of merocyanine and a light-induced compact shell arrangement extend its half-life from 47 minutes to over 154 hours, significantly boosting singlet oxygen output. The nano-photosensitizer also shows high biocompatibility and notably inhibits tau protein aggregation in neural cells, even with phosphatase inhibitors. Further, it promotes dendritic growth in neuro cells, doubling typical lengths. This work not only advances chemical nanotechnology but also sets a foundation for developing long-lasting phototherapy agents for treating neurodegenerative diseases., (© 2024 Wiley-VCH GmbH.)

Photothermal therapy (PTT) is a promising technology that can achieve the thermal ablation of tumors and induce immunogenic cell death (ICD). However, relying solely on the antitumor immune responses caused by PTT-induced ICD is insufficient to suppress tumor metastasis and recurrence effectively. Fortunately, multifunctional nanoformulation-based synergistic photothermal immunotherapy can eliminate primary and metastatic tumors and inhibit tumor recurrence for a long time. Herein, we select polydopamine (PDA) nanoparticles to serve as the carrier for our nanomedicine as well as a potent photothermal agent and modulator of macrophage polarization. PDA nanoparticles are loaded with the insoluble immune adjuvant Imiquimod (R837) to construct PDA(R837) nanoformulations. These straightforward yet highly effective nanoformulations demonstrate excellent performance, allowing for successful triple-negative breast cancer (TNBC) treatment through synergistic photothermal immunotherapy. Moreover, experimental results showed that PDA(R837) implementation of PTT is effective in the thermal ablation of primary tumors while causing ICD and releasing R837, further promoting dendritic cell (DC) maturation and activating the systemic antitumor immune response. Furthermore, PDA(R837) nanoformulations inhibit tumor metastasis and recurrence and achieve M1 phenotype macrophage polarization, achieving long-term and excellent antitumor efficacy. Therefore, the structurally simple PDA(R837) nanoformulations provide cancer treatment and have excellent clinical translational application prospects.

The application of the bionematicides derived from microorganisms and their secondary metabolites represents a promising strategy for managing root-knot nematodes. In this study, a nematicidal compound, cis -3-indoleacrylic acid, was isolated from Streptomyces youssoufiensis YMF3.862. This compound caused Meloidogyne incognita juveniles to have swollen bodies with apparent cracks on the cuticle surface. The LC 50 value of cis -3-indoleacrylic acid against juveniles was 16.31 μg/mL 24 h of post-treatment. Cis -3-indoleacrylic acid at 20 μg/mL significantly inhibited V-ATPase expression and remarkably decreased enzyme activity by 84.41%. As an inhibitor of V-ATPase, cis -3-indoleacrylic acid caused significant H + accumulation in nematode bodies, resulting in lower intracellular pH values and higher extracellular pH values of M. incognita . Application of 50 μg/mL cis -3-indoleacrylic acid generated a 71.06% control efficiency against M. incognita on tomatoes. The combination results of this study indicated that cis -3-indoleacrylic acid can be developed as a natural nematicide for controlling M. incognita .

Postoperative adhesion (PA) is a severe complication of abdominal surgery caused by the inability of clinical physical barriers to cope with diverse pathological factors in the process of PA formation. Herein, we described a multifunctional hydrogel composed of bioactive nanoparticles (BNs) and dual-responsive hydrogel to serve as a combination of physical and pharmacological therapy for preventing PA. Specifically, BNs with pro-inflammatory cell-targeted aggregation were designed by integrating hyaluronic acid onto the polydopamine (PDA)-coated hollow ZrO 2 nanoparticles loaded with antimicrobial peptides and platelet lysates that can eliminate bacterial infection and promote tissue repair. PDA can remove the excessive reactive oxygen species (ROS) and thus suppress the oxidative stress damage and accompanying inflammation in the presence of high ROS. The dynamically cross-linked host hydrogel presents injectable yet microenvironment-responsive properties, which enables complete coverage of the uneven tissue and instantly forms a physical barrier to effectively isolate injured tissues and neighboring organs, and synchronously acts as a niche to deliver the BNs in a controlled way. The hydrogel demonstrates a remarkable antiadhesion effect in a rat cecum-abdominal wall adhesion model. Together, this "all-in-one" composite hydrogel strategy capable of a physical barrier capability and pharmacological effects represents a promising clinical solution to prevent PA.

Tryptophan not only serves as a fundamental building block for protein synthesis but also acts as a metabolic precursor for a diverse array of high-value chemicals. Although a few tryptophan-responsive biosensors are currently available, there is a growing interest in developing high-performance biosensors. In this study, we create a miniature toolkit of tryptophan biosensors based upon the leader regulatory region of the tnaCAB operon, which is responsible for tryptophan catabolism in Escherichia coli . Four variants are generated by engineering the tnaC leader sequence, which encodes a leader peptide composed of 24 amino acid residues. Subsequently, the performance of both the natural tnaC sequence and its engineered variants is assessed in a reporter strain based on the MazEF toxin-antitoxin system. The results demonstrate that two engineered variants exhibit increased sensitivity to low levels of tryptophan. Moreover, the engineered biosensors are further optimized by replacing the native promoter of tnaC with a phage-derived constitutive promoter. Intriguingly, the engineered biosensors can be reconstructed for extended application in Pseudomonas putida , a robust microbial chassis for metabolic engineering. In summary, our study expands the toolkit of tryptophan biosensors that can be broadly used for the bioproduction of many other high-value tryptophan-derived products.

Influenza viruses that cause seasonal and pandemic flu are a permanent health threat. The surface glycoprotein, neuraminidase, is crucial for the infectivity of the virus and therefore an attractive target for flu drug discovery campaigns. We have designed and synthesized more than 40 3-indolinone derivatives. We mainly investigated the role of substituents at the 2 position of the core as well as the introduction of substituents or a nitrogen atom in the fused phenyl ring of the core for inhibition of influenza virus neuraminidase activity and replication in vitro and in vivo. After evaluating the compounds for their ability to inhibit the viral neuraminidase, six potent inhibitors 3c, 3e, 7c, 12o, 12v, 18d were progressed to evaluate for cytotoxicity and inhibition of influenza virus A/PR/8/34 replication in in MDCK cells. Two hit compounds 3e and 12o were tested in an animal model of influenza virus infection. Molecular mechanism of the 3-indolinone derivatives interactions with the neuraminidase was revealed in molecular dynamic simulations. Proposed inhibitors bind to the 430-cavity that is different from the conventional binding site of commercial compounds. The most promising 3-indolinone inhibitors demonstrate stronger interactions with the neuraminidase in molecular models that supports proposed binding site., 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 Masson SAS. All rights reserved.)

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga, which significantly reduced TG accumulation with an EC 50 value of 0.07 μM and showed relatively low cytotoxicity with an IC 50 value of around 24 μM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d. A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity., 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 Masson SAS. All rights reserved.)

Herein, a series of new 1,1,2-trimethyl-1H-benzo[e]indole dyes was prepared via Knoevenagel condensation reaction between 1,1,2-trimethyl-1H-benzo[e]indole and benzaldehydes, and characterized using various spectroscopic methods. The obtained compounds showed cytotoxic properties in G361 melanoma cell line upon irradiation with 414 nm blue light at submicromolar doses. The mechanism of action of the most potent compound 15 was further investigated. The treatment induced substantial generation of reactive oxygen species, leading to DNA damage followed by cell death depending on the concentration of the photosensitizer compound and the irradiation intensity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A patent application titled '1,1-Dimethyl-2-[(E)-2-Phenylethenyl]-1H-benzo[e]indole Derivatives and Uses Thereof' (U.S. App. 18/456,145) has been filed by Gabriele Varvuolyte, Eva Reznickova, Sonata Krikstolaityte (currently - Sonata Krikstole), Aurimas Bieliauskas, Veronika Vojackova, Neringa Kleiziene, Egle Arbaciauskiene, Asta Zukauskaite, Vladimir Krystof and Algirdas Sackus. Any additional authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)- b -poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide ( p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium .

In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C 20 H 15 N 5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl 2 (C 20 H 15 N 5 )] n (pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl 2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC 50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC 50 value of 4.88 µM, outperforming both 2-DPHI and CdCl 2 . Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT-IR, 1 H NMR, 13 C NMR and UV-Vis spectroscopy.

The chemical synthesis of N -acyl indoles is hindered by the poor nucleophilicity of indolic nitrogen, necessitating the use of strongly basic reaction conditions that encumber elaboration of highly functionalized scaffolds. Herein, we describe the total chemoenzymatic synthesis of the bulbiferamide natural products by the biochemical activity reconstitution of a nonribosomal peptide synthetase assembly line-derived (NRPS-derived) thioesterase that neatly installs the macrocyclizing indolylamide. The enzyme represents a starting point for biocatalytic access to macrocyclic indolylamide peptides and natural products.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, driven mainly by chronic hepatitis infections and metabolic disorders, which highlights the urgent need for novel therapeutic strategies. Sirtuins, particularly SIRT1 are crucial in HCC pathogenesis, making it a promising drug target. Indole-based molecules show potential as therapeutic agents by interacting with key proteins like sirtuins involved in cancer progression. In this study, we designed and synthesized novel indole-based small molecules and investigated their potential sirtuin inhibitory action and anticancer activity on HCC cell lines. Four of the twenty-eight tested small molecules on different cancer types were selected (4 g, 4 h, 4o, and 7j) based on their structure-activity relationship and studied on a panel of HCC cell lines. Compounds had active drug-target interactions with SIRT1 or SIRT2 based on DEEPScreen DTI predictions and docking studies which confirmed that 4o, 4 g, and 7j were most potent in their interaction with SIRT1. Compound 4 g caused the highest sirtuin activity inhibition in vitro and induced G1 arrest and apoptosis in HCC cell lines., (© 2024 Wiley Periodicals LLC.)

Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer., Competing Interests: Declaration of competing interest The author 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.)

In this paper, we designed a novel "Freeze-thaw" type hydrogel microneedle (PP-CDLut-AMY MN). The "Freeze-thaw" cycle endows the MN excellent water absorption, with a dissolution rate of up to 486 %. The addition of polydopamine@polypyrrole (PP) enabled the MN to have a stable temperature increase to approximately 50 °C under near-infrared light irradiation, which exhibited killing rates of 99 % and 98 % against free S. aureus and E. coli, respectively. Natural macromolecule α-Amylase (AMY) was used as a bacterial biofilm disintegrator, and the destruction rate of S. aureus biofilm reached 83.2 %. Meanwhile, the incorporation of Hydroxypropyl-β-cyclodextrin @Luteolin (CDLut) provided the MN with good antioxidant properties, which could scavenge 73.35 % of DPPH free radicals. In vivo experiments have shown that the MN can effectively promote the healing of wounds infected by S. aureus biofilm and that the stable and gentle photothermal effect did not cause unnecessary damage to the surrounding tissues. We believe that this novel hydrogel MN has great potential to combat bacterial biofilms associated with wound infections., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

With the prevalence of drug-resistant bacteria and the waning effects of antibiotics, nanoplatform has become an effective strategy for fighting infections. This work reports a dipolar-hollowed α-Fe 2 O 3 @Au/Polydopamine (PDA) nanospindle which possesses both photothermal-photodynamic (PTT-PDT) coupling antibacterial and drug carrying performance. Firstly, the spindle type α-Fe 2 O 3 @Au/PDA particle was prepared by a simple one-step strategy and then the dipolar-hollow structure was obtained by controlling etching the inside α-Fe 2 O 3 core with hydrochloric acid. After further loading the photosensitizer zinc phthalocyanine (ZnPc), the dipolar-hollowed α-Fe 2 O 3 @Au/PDA-ZnPc nanospindles were obtained. Owing to the dipolar-hollowed interior, the nanospindles are also effective in carrying antitumor drug doxorubicin (DOX) and shows a good drug loading-release behavior. The dipolar-hollowed α-Fe 2 O 3 @Au/PDA nanospindles exhibits a high antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) under near-infrared (NIR) and Xenon lamp irradiation. When α-Fe 2 O 3 @Au/PDA-ZnPc nanospindles concentration was increased to 100 μg/mL, the antibacterial rate was close to 100 %. In comparison to the original α-Fe 2 O 3 @Au/PDA nanospindles, the product achieved a lower effective antibacterial temperature. This triple-mode therapy (PTT/PDT/Drug) provides an interesting design idea for anisotropic therapeutic nanoplatform which can be applied in low-temperature antibacterial and drug delivery., 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.)

Developing titanium-based dental implants with both excellent antibacterial properties and good osseointegration is crucial for the success of the implant operation and the long-term durability of the implant. In this study, a polydopamine-based coating was created by attaching TiO 2 nanosheets-cyanine composites onto the titanium surface, enabling the integration of effective photothermal antibacterial therapy with osseointegration. The exceptional dual-photothermal conversion abilities of polydopamine and cyanine in the coating resulted in outstanding photothermal antibacterial and antibiofilm therapy against four types of bacteria. Furthermore, TiO 2 nanosheets promoted the adhesion, proliferation and early osteogenic differentiation of osteoblasts. In an infected dental implant model in rats, the developed coating exhibited potent antibacterial activity and remarkable osteogenic differentiation in the bone, leading to increased bone formation around the implants. This innovative approach, combining photothermal therapy with osteogenic two-dimensional nanomaterials, presents a novel method for surface functionalization of implants to achieve effective antibacterial and osseointegration capabilities., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer., 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 Masson SAS.. All rights reserved.)

As the application of conductive hydrogels in the field of wearable smart devices is gradually deepening, a variety of hydrogel sensors with high mechanical properties, strong adhesion, fast self-healing, and excellent conductivity are emerging. However, it is still a great challenge to manufacture hydrogel sensors combining multiple properties. Herein, we leveraged the dynamic redox reaction occurring between polydopamine (PDA) and Fe 3+ to induce ammonium persulfate (APS) to generate free radicals, thereby initiating the copolymerization of hydroxyethyl methacrylate (HEMA) and acrylic acid (AA) monomers. Then, polypyrrole-encapsulated cellulose nanofibers (PPy@CNF) and carboxymethylcellulose (CMC) were incorporated as conductive reinforced nanofillers and interpenetrating network skeleton. The obtained hydrogel cross-linked through reversible metal-ligand bonds, π-π stacking and abundant hydrogen bonding demonstrated great mechanical properties (strength 240.4 kPa, strain 1175 %) and self-healing ability (88.96 %). Particularly, the gel displayed ultrahigh durability and skin adhesive ability (75 kPa after 10 cycles), surpassing previous skin adhesion hydrogels. Furthermore, through the synergistic conductive effect of PPy@CNF and Fe 3+ , the prepared hydrogel sensor possessed high sensitivity (GF = 1.89) with a wide sensing range (~1000 %), which could realize the human body's daily motion detection, and had a promising application in flexible wearable electronics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oral biotherapeutics hold significant promise, but their lack of controllability and targeting poses a major challenge, particularly for intestinal bacterial biotherapeutics. In response, we have developed a nanoencapsulation approach that responds to the release of enzyme activity in the organism and activates the enzyme in situ, allowing for controlled colonization of microbes in the gut. The nano-coating comprises a two-layer structure: an inner layer of polydopamine with photothermal and adhesive properties, and an outer layer of gelatin-sodium carboxymethylcellulose, which is hydrolyzed by cellulases in the gut following photothermal interaction with dopamine. We have successfully achieved controlled colonization of a wide range of microorganisms. Furthermore, in a diabetes model, this approach has had a profound impact on regulating glucagon-like peptide-1 (GLP-1) production, β-cell physiology, and promoting insulin secretion. This nanocoating is achieved by in situ activation of cellulase without the need for genetic or targeted molecular modification, representing a new paradigm and alternative strategy for microbial therapy. It not only enables precise and controlled colonization of probiotics but also demonstrates great potential for broader application in the field of oral biotherapy. STATEMENT OF SIGNIFICANCE: We have developed a nano-encapsulation method that triggers enzyme activity in response to enzymatic activity, resulting in the controlled release and adhesion of a wide range of microorganisms in the gut. The nano coating comprises two layers: an inner layer of polydopamine with photothermal and adhesion properties, and an outer layer of a gelatin-sodium carboxymethylcellulose polymer, which can be hydrolyzed by cellulases in the intestine. Additionally, this method allows for the preparation of various microbial coatings. This approach holds significant promise for regulating GLP-1 production, the physiological function of pancreatic β-cells, and promoting insulin secretion in diabetes models., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The adsorptive removal of amphoteric antibiotics like doxycycline (DOX) is a difficult task because of the electrostatic repulsion between these amphoteric molecules and adsorbents. For this purpose, a zwitter adsorbent was fabricated by incorporating zwitter ZIF-67/MIL-88A binary MOF into the matrix of alginate (Alg); in addition, the surface of the beads was modified by polydopamine (PDA). The batch experiments implied the super-high adsorption efficacy of ZIF-67/MIL-88A@Alg@PDA toward DOX attained 384.61 ± 5.08 mg/g at a neutral pH medium, 25 °C, and using 0.02 g. The isotherm analysis implied the physisorption of DOX onto ZIF-67/MIL-88A@Alg@PDA, while the kinetic analysis denoted the chemisorption of DOX. The results of XPS, Zeta potential, and Lab experiments identified the types of physical and chemical interactions between ZIF-67/MIL-88A@Alg@PDA and DOX. The durability of the ZIF-67/MIL-88A@Alg@PDA beads was inspected by the recycling test, clarifying that the DOX adsorption aptitude declined by 12.22 mg/g. In addition, the measured leaching concentrations of cobalt and iron from the leaching test were 0.008 and 0.098 mg/L. The ionic strength of ZIF-67/MIL-88A@Alg@PDA, implying an enhancement in the DOX removal (%) from 83.51 to 93.50 % by raising the NaCl concentration from 0.2 to 1.0 mol/L. Therefore, our study could provide a simple procedure to overcome the electrostatic repulsion that retard the adsorption process of the amphoteric drugs onto charged adsorbents with positive or negative charges. Additionally, this procedure could also generate an electrostatic interaction between the zwitter adsorbents and the amphoteric drugs at specific pH media when they are in a zwitterionic nature., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohammed Salah Ayoup reports was provided by Alexandria University. 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 B.V. All rights reserved.)

Bacterial infection, reactive oxygen species (ROS) accumulation, and persistent inflammation pose significant challenges in the treatment of periodontitis. However, the current single-modal strategy makes achieving the best treatment effect difficult. Herein, we developed a double-network hydrogel composed of Pluronic F127 (PF-127) and hyaluronic acid methacrylate (HAMA) loaded with spermidine-modified mesoporous polydopamine nanoparticles (M@S NPs). The PF-127/HAMA/M@S (PH/M@S) hydrogel was injectable and exhibited thermosensitivity and photocrosslinking capabilities, which enable it to adapt to the irregular shape of periodontal pockets. In vitro, the PH/M@S displayed multiple therapeutic effects, such as photothermal antibacterial activity, a high ROS scavenging capacity, and anti-inflammatory effects, which are beneficial for the multimodal treatment of periodontitis. The underlying anti-inflammatory mechanism of this hydrogel involves suppression of the extracellular regulated protein kinase 1/2 and nuclear factor kappa-B signalling pathways. Furthermore, in lipopolysaccharide-stimulated macrophage conditioned media, the PH/M@S effectively restored the osteogenic differentiation potential. In a rat model of periodontitis, the PH/M@S effectively reduced the bacterial load, relieved local inflammation and inhibited alveolar bone resorption. Collectively, these findings highlight the versatile functions of the PH/M@S, including photothermal antibacterial activity, ROS scavenging, and anti-inflammatory effects, indicating that this hydrogel is a promising multifunctional filling material for the treatment of periodontitis., 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.)

The disappearance of the protective barrier after skin injury leads to the overproduction of reactive oxygen species (ROS) in response to various stimuli. Oxidative stress is one of the most important causes of delayed wound healing, leading to negative outcomes, such as excessive inflammatory response and impaired angiogenesis. In this study, we used microfluidic technology to integrate Prussian blue nanozymes and vascular endothelial growth factor and constructed multifunctional microspheres that improved local oxidative stress. In order to enhance the adhesion of the microspheres on the wound surface and prolong the release of the drug, we coated them with dopamine, ensuring uniform encapsulation on their surface. The microspheres adhered well to the wound surface and promoted wound healing by scavenging ROS, reducing the inflammatory response, and promoting angiogenesis. This strategy of integrating nanozymes and growth factors can have a synergistic effect, which is significant for wound healing., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ferroptosis primarily relies on reactive oxygen (ROS) production and lipid peroxide (LPO) accumulation, which opens up new opportunities for tumor therapy. However, a standalone ferroptosis process is insufficient in inhibiting tumor progression. Unlike previously reported Fe-based nanomaterials, we have engineered a novel nanoreactor named IR780/Ce@EGCG/APT, which uses metal-polyphenols network (Ce@EGCG) based on rare-earth cerium and epigallocatechin gallate (EGCG) to encapsulate IR780 and modified with the aptamer (AS1411). The intricately designed nanoreactor is specifically taken up by tumor cells, releasing Ce 3+ , EGCG, and IR780. On the one hand, Ce 3+ triggers ROS production via a Fenton-like reaction, inducing ferroptosis in tumor cells. On the other hand, IR780 accumulates in mitochondria and disrupts mitochondrial function upon laser irradiation, leading to tumor cell apoptosis. EGCG serves as a sensitizer, simultaneously enhancing the sensitivity of tumor cells to ferroptosis and photothermal therapy. After a single dose and three times of 808 nm laser irradiation for treatment, it has been observed that the nanoreactor induces dendritic cells (DCs) maturation, facilitates cytotoxic T lymphocyte infiltration, improves immunosuppressive microenvironment, activates the systemic immune system, and generates long-term immune memory., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Nintedanib (NIN), a multi-tyrosine kinase inhibitor clinically approved for idiopathic pulmonary fibrosis and lung cancer, is characterized by protonation-dependent lysosomotropic behavior and appearance of lysosome-specific fluorescence emission properties. Here we investigate whether spontaneous formation of a so far unknown NIN matter within the acidic cell compartment is underlying these unexpected emissive properties and investigate the consequences on lysosome functionality. Lysosomes of cells treated with NIN, but not non-protonatable NIN derivatives, exhibited lysosome-associated birefringence signals co-localizing with the NIN-derived fluorescence emission. Sensitivity of both parameters towards vATPase inhibitors confirmed pH-dependent, spontaneous adoption of novel crystalline NIN structures in lysosomes. Accordingly, NIN crystallization from buffer solutions resulted in formation of multiple crystal polymorphs with pH-dependent fluorescence properties. Cell-free crystals grown at lysosomal-like pH conditions resembled NIN-treated cell lysosomes concerning fluorescence pattern, photobleaching dynamics, and Raman spectra. However, differences in birefringence intensity and FAIM-determined anisotropy, as well as predominant association with (intra)lysosomal membrane structures, suggested formation of a semi-solid NIN crystalline matter in acidic lysosomes. Despite comparable target kinase inhibition, NIN, but not its non-protonatable derivatives, impaired lysosomal functionality, mediated massive cell vacuolization, enhanced autophagy, deregulated lipid metabolism, and induced atypical phospholipidosis. Moreover, NIN exerted distinct phototoxicity, strictly dependent on lysosomal microcrystallization events. The spontaneous formation of NIN crystalline structures was also observable in the gut mucosa of orally NIN-treated mice. Summarizing, the here-described kinase inhibition-independent impact of NIN on lysosomal functionality mediates several of its cell biological activities and might contribute to NIN adverse effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All 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.)

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.)

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.)