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Ubiquitous antibiotics threaten human health and ecosystem sustainability, and existing removal strategies, especially conventional multistep water treatments, are primarily limited by the antibiotic-specific removal capability. Here, we explore the natural biomass, plant polyphenols, in the capture of various antibiotics with a facile treatmentâpolyphenol-mediated antibiotic-independent supramolecular coagulation (PMAC). The PMAC shows a superior performance in removing five tetracyclines and quinolones (up to 98.54%), even under complex environmental parameters, including different pH, the presence of inorganic particles and ionic strength, and the presence of conventional colloid-associated contaminants. Our mechanistic studies suggested that PMAC is capable of exerting multiple molecular interactions with various antibiotics, and the coordination-driven self-assembly further destabilizes the phenolic-antibiotic nanocomplexes, enabling an antibiotic-independent coagulation. Collectively, the combination of efficient remediation with inexpensive biomass suggests a simple and scalable method for the sustainable removal of antibiotics. Our strategy shows great promise as a cost-effective, facile approach to eliminate antibiotics capable of being integrated into the currently existing water treatment systems.
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Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.
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Nanopartículas , Polifenóis , Polifenóis/química , Nanopartículas/química , Animais , Camundongos , Ibuprofeno/química , Portadores de Fármacos/química , Humanos , Albuminas/química , Soroalbumina Bovina/químicaRESUMO
Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.
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Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.
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Neoplasias , Vacinas , Humanos , Imunoterapia , Lipopolissacarídeos , Neoplasias/terapia , Microambiente Tumoral , Vacinas AnticâncerRESUMO
Nature has exhibited a high degree of control over the structures and functions. Supramolecules have been utilized to mimic the subtle assembly in nature. However, sophisticated synthesis of molecular skeletons or programmable design of the driving forces raises great challenges in fabricating high-level superstructures in a controlled manner. Natural polyphenols show great promises as building blocks for a diverse of assemblies with controlled structures and functionalities. The intrinsically embedded phenolic groups (i. e., catechol and galloyl groups) are readily forming multiple molecular interactions, including coordination, hydrogen bonding, and π-π interactions with various materials of inorganic particles, organic compounds, synthetic polymers, and biomacromolecules, providing the self-assembled structures or nanocoating on surfaces. Subsequent assembly occurred by further bonding of polyphenols to construct supraparticles. To gain control over the self-assembly, the key lies in the interplay among the molecular interactions with one or two being dominant. In this Perspective, we introduce the representative polyphenol-based assemblies and their derived supraparticles to exhibit the effective harness of the controlled self-assembly by polyphenols.
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OBJECTIVE: This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). METHODS: A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. RESULTS: Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aß and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. CONCLUSIONS: Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD.
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Disfunção Cognitiva , Transtornos de Estresse Pós-Traumáticos , Humanos , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Estudos Longitudinais , Neuroimagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
Polydopamine is a remarkable molecule that has gained considerable attention for its role in material surface modification, leading to an abundance of research in the biomaterial domain. While its widespread use is well documented, the molecule's potential cellular interactions have been less explored. In particular, dopamine serves as a neurotransmitter and a hormone that interacts with dopamine receptors in cells. Our study sheds light on the previously unexamined interaction between polydopamine and dopamine receptor D1 (DRD1). We discovered that polydopamine, along with its derivatives, such as levodopa and catechol, can activate DRD1âa function previously attributed solely to dopamine. Moreover, we found that polydopamine has the ability to influence cell behavior through the cAMP/PKA pathway, thereby affecting RhoA activity and stress fiber formation. These observations invite further consideration regarding the biological safety of polydopamine in biomedical contexts and also open avenues for new research directions in designing bioactive functional materials.
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Dopamina , Levodopa , Dopamina/metabolismo , Polímeros/farmacologia , Indóis/farmacologiaRESUMO
Pullulanase is a starch-debranching enzyme that hydrolyzes side chain of starch, oligosaccharides and pullulan. Nevertheless, the limited activities of pullulanases constrain their practical application. Herein, the hyperthermophilic type II pullulanase from Pyrococcus yayanosii CH1 (PulPY2) was evolved by synergistically engineering the substrate-binding pocket and active-site lids. The resulting mutant PulPY2-M2 exhibited 5-fold improvement in catalytic efficiency (kcat/Km) compared to that of PulPY2. PulPY2-M2 was utilized to develop a one-pot reaction system for efficient production of maltooligosaccharides. The maltooligosaccharides conversion rate of PulPY2-M2 reached 96.1%, which was increased by 5.4% compared to that of PulPY2. Furthermore, when employed for glucose production, the glucose productivity of PulPY2-M2 was 25.4% and 43.5% higher than that of PulPY2 and the traditional method, respectively. These significant improvements in maltooligosaccharides and glucose production and the efficient utilization of corn starch demonstrated the potential of the engineered PulPY2-M2 in starch sugar industry.
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Glucose , Amido , Amido/química , Zea mays/metabolismo , Glicosídeo Hidrolases/metabolismo , Oligossacarídeos/química , Archaea , Especificidade por SubstratoRESUMO
Rationale: Device implantation frequently triggers cardiac remodeling and fibrosis, with monocyte-driven inflammatory responses precipitating arrhythmias. This study investigates the role of m6A modification enzymes METTL3 and METTL14 in these responses and explores a novel therapeutic strategy targeting these modifications to mitigate cardiac remodeling and fibrosis. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with ventricular septal defects (VSD) who developed conduction blocks post-occluder implantation. The expression of METTL3 and METTL14 in PBMCs was measured. METTL3 and METTL14 deficiencies were induced to evaluate their effect on angiotensin II (Ang II)-induced myocardial inflammation and fibrosis. m6A modifications were analyzed using methylated RNA immunoprecipitation followed by quantitative PCR. NF-κB pathway activity and levels of monocyte migration and fibrogenesis markers (CXCR2 and TGF-ß1) were assessed. An erythrocyte microvesicle-based nanomedicine delivery system was developed to target activated monocytes, utilizing the METTL3 inhibitor STM2457. Cardiac function was evaluated via echocardiography. Results: Significant upregulation of METTL3 and METTL14 was observed in PBMCs from patients with VSD occluder implantation-associated persistent conduction block. Deficiencies in METTL3 and METTL14 significantly reduced Ang II-induced myocardial inflammation and fibrosis by decreasing m6A modification on MyD88 and TGF-ß1 mRNAs. This disruption reduced NF-κB pathway activation, lowered CXCR2 and TGF-ß1 levels, attenuated monocyte migration and fibrogenesis, and alleviated cardiac remodeling. The erythrocyte microvesicle-based nanomedicine delivery system effectively targeted inflamed cardiac tissue, reducing inflammation and fibrosis and improving cardiac function. Conclusion: Inhibiting METTL3 and METTL14 in monocytes disrupts the NF-κB feedback loop, decreases monocyte migration and fibrogenesis, and improves cardiac function. Targeting m6A modifications of monocytes with STM2457, delivered via erythrocyte microvesicles, reduces inflammation and fibrosis, offering a promising therapeutic strategy for cardiac remodeling associated with device implantation.
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Fibrose , Metiltransferases , Monócitos , NF-kappa B , Humanos , Metiltransferases/metabolismo , Metiltransferases/genética , Monócitos/metabolismo , Masculino , Animais , NF-kappa B/metabolismo , Eritrócitos/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Feminino , Metilação , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Micropartículas Derivadas de Células/metabolismo , Leucócitos Mononucleares/metabolismo , Angiotensina II/metabolismo , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Remodelação Ventricular , Miocárdio/metabolismo , Miocárdio/patologia , Nanomedicina/métodosRESUMO
Pullulanases are important starch-debranching enzymes that mainly hydrolyze the α-1,6-glycosidic linkages in pullulan, starch, and oligosaccharides. Nevertheless, their practical applications are constrained because of their poor activity and low thermostability. Moreover, the trade-off between activity and thermostability makes it challenging to simultaneously improve them. In this study, an engineered pullulanase was developed through reshaping the active-site tunnel and engineering the surface lysine residues using the pullulanase from Pyrococcus yayanosii CH1 (PulPY2). The specific activity of the engineered pullulanase was increased 3.1-fold, and thermostability was enhanced 1.8-fold. Moreover, the engineered pullulanase exhibited 11.4-fold improvement in catalytic efficiency (kcat/Km). Molecular dynamics simulations demonstrated an anti-correlated movement around the entrance of active-site tunnel and stronger interactions between the surface residues in the engineered pullulanase, which would be beneficial to the activity and thermostability improvement, respectively. The strategies used in this study and dynamic evidence for insight into enzyme performance improvement may provide guidance for the activity and thermostability engineering of other enzymes.