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1.
ACS Macro Lett ; : 1456-1462, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39404655

RESUMEN

The self-assembly of sequence-defined polymers (SDPs) enables the formation of a diverse array of nanostructures; however, the construction of complex hierarchical structures via thermal annealing from SDPs remains relatively unexplored. In this study, two series of oligourethanes, 2Cit-pBn-OH and 2Cit-mBn-OH, were synthesized to investigate their thermal annealing behaviors. Nanorod clusters were generated from 2Cit-pB6-OH in a mixture of 1,4-dioxane and toluene, whereas 2Cit-pB8-OH formed nanosheets after thermal annealing. Upon modifying the structure of the repeating units, 2Cit-mB6-OH self-assembled into ultrathin nanosheets, transitioning from nanospheres after thermal annealing in a mixture of isopropanol and cyclohexane, while "flower" micelles were produced from 2Cit-mB8-OH. Interestingly, when isopropanol was replaced with a mixture of isopropanol and tetrahydrofuran (THF), uniform nanotubes were generated by 2Cit-mB6-OH under the same thermal annealing conditions. Additionally, a discrete amphiphile (2Cit-mB4-(S)DPEG) was synthesized, leading to the formation of uniform nanosheets in aqueous solution after thermal annealing. This work highlights the significant effects of sequence and repeating unit structure of SDPs on their self-assembly behaviors and presents a novel strategy for the controlled fabrication of unique nanostructures from SDPs.

2.
Molecules ; 29(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39275079

RESUMEN

Three small donor molecule materials (S1, S2, S3) based on dithiophene [2,3-d:2',3'-d']dithiophene [1,2-b:4,5-b']dithiophene (DTBDT) utilized in this study were synthesized using the Vilsmeier-Haack reaction, traditional Stille coupling, and Knoevenagel condensation. Then, a variety of characterization methods were applied to study the differences in optical properties and photovoltaic devices among the three. By synthesizing S2 using a thiophene π-bridge based on S1, the blue shift in ultraviolet absorption can be enhanced, the band gap and energy level can be reduced, the open circuit voltage (VOC) can be increased to 0.75 V using the S2:Y6 device, and a power conversion efficiency (PCE) of 3% can be achieved. Also, after developing the device using Y6, S3 introduced the alkyl chain of thiophene π-bridge to S2, which improved the solubility of tiny donor molecules, achieved the maximum short-circuit current (JSC = 10.59 mA/cm2), filling factor (FF = 49.72%), and PCE (4.25%). Thus, a viable option for future design and synthesis of small donor molecule materials is to incorporate thiophene π-bridges into these materials, along with alkyl chains, in order to enhance the device's morphology and charge transfer behavior.

3.
ACS Nano ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263977

RESUMEN

The selective upregulation of intracellular oxidative stress in cancer cells presents a promising approach for effective cancer treatment. In this study, we report the integration of enzyme catalytic amplification and chemical amplification reactions in ß-lapachone (Lap)-loaded micellar nanoparticles (NPs), which are self-assembled from reactive oxygen species (ROS)-responsive self-immolative polymers (SIPs). This integration enables cyclic amplification of intracellular oxidative stress in cancer cells. Specifically, we have developed ROS-responsive SIPs with phenylboronic ester triggering motifs and hexafluoroisopropanol moieties in the side chains, significantly enhancing Lap loading efficiency (98%) and loading capacity (33%) through multiple noncovalent interactions. Upon ROS activation in tumor cells, the Lap-loaded micellar NPs disassemble, releasing Lap and generating additional ROS via enzyme catalytic amplification. This process elevates intracellular oxidative stress and triggers polymer depolymerization in a positive feedback loop. Furthermore, the degradation of SIPs via chemical amplification produces azaquinone methide intermediates, which consume intracellular thiol-related substrates, disrupt intracellular redox hemostasis, further intensify oxidative stress, and promote cancer cell apoptosis. This work introduces a strategy to enhance intracellular oxidative stress by combining enzymatic and chemical amplification reactions, providing a potential pathway for the development of highly efficient anticancer agents.

4.
Angew Chem Int Ed Engl ; : e202415588, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305234

RESUMEN

Electron beam (EB) and extreme ultraviolet (EUV) lithography are advanced techniques capable of achieving sub-10 nm resolutions, critical for fabricating next-generation nanostructures and semiconductor devices. However, developing EUV photoresists that meet all demands for resolution, line edge roughness (LER), and sensitivity (RLS) remains a significant challenge. Herein, we introduce high-performance photoresists based on single-component self-immolative polymers (SIPs) with inherent signal amplification via cascade degradation. These SIPs function as dual-tone photoresists under both EB and EUV lithography, with performance primarily determined by the exposure dose. Lithographic evaluations show that discrete SIPs provide significant improvements over disperse counterparts, achieving higher resolution and reduced LER. Specifically, a discrete SIP with a DP of 12 produces a line-space pattern with a resolution of approximately 18 nm and an LER of 1.8 nm, compared to 21 nm resolution and 2.5 nm LER for disperse SIPs. Additionally, these SIP-based photoresists, enriched with aromatic structures, exhibit excellent etch resistance. The single-component nature and potential to address the RLS trade-off underscore the promise of discrete SIPs for EUV lithography.

5.
Biomacromolecules ; 25(9): 5402-5416, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39105715

RESUMEN

Peptides and polypeptides feature a variety of active functional groups on their side chains (including carboxylic acid, hydroxyl, amino, and thiol groups), enabling diverse chemical modifications. This versatility makes them highly valuable in stimuli-responsive systems. Notably, pH-responsive peptides and polypeptides, due to their ability to respond to pH changes, hold significant promise for applications in cellular pathology and tumor targeting. Extensive researches have highlighted the potentials of low pH insertion peptides (pHLIPs), peptide-drug conjugates (PDCs), and antibody-drug conjugates (ADCs) in biomedicine. Peptide self-assemblies, with their structural stability, ease of regulation, excellent biocompatibility, and biodegradability, offer immense potentials in the development of novel materials and biomedical applications. We also explore specific examples of their applications in drug delivery, tumor targeting, and tissue engineering, while discussing future challenges and potential advancements in the field of pH-responsive self-assembling peptide-based biomaterials.


Asunto(s)
Sistemas de Liberación de Medicamentos , Péptidos , Concentración de Iones de Hidrógeno , Péptidos/química , Humanos , Sistemas de Liberación de Medicamentos/métodos , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Animales , Neoplasias/tratamiento farmacológico , Inmunoconjugados/química
6.
Biomacromolecules ; 25(9): 5454-5467, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39196319

RESUMEN

The fundamental building block of living organisms is the cell, which is the universal biological base of all living entities. This micrometric mass of cytoplasm and the membrane border have fascinated scientists due to the highly complex and multicompartmentalized structure. This specific organization enables numerous metabolic reactions to occur simultaneously and in segregated spaces, without disturbing each other, but with a promotion of inter- and intracellular communication of biomolecules. At present, artificial nano- and microcompartments, whether as single components or self-organized in multicompartment architectures, hold significant value in the study of life development and advanced functional materials and in the fabrication of molecular devices for medical applications. These artificial compartments also possess the properties to encapsulate, protect, and control the release of bio(macro)molecules through selective transport processes, and they are capable of embedding or being connected with other types of compartments. The self-assembly mechanism of specific synthetic compartments and thus the fabrication of a simulated organelle membrane are some of the major aspects to gain insight. Considerable efforts have now been devoted to design various nano- and microcompartments and understand their functionality for precise control over properties. Of particular interest is the use of polymeric vesicles for communication in synthetic cells and colloidal systems to reinitiate chemical and biological communication and thus close the gap toward biological functions. Multicompartment systems can now be effectively created with a high level of hierarchical control. In this way, these structures can not only be explored to deepen our understanding of the functional organization of living cells, but also pave the way for many more exciting developments in the biomedical field.


Asunto(s)
Células Artificiales , Polímeros , Células Artificiales/química , Células Artificiales/metabolismo , Polímeros/química , Humanos
7.
Angew Chem Int Ed Engl ; 63(42): e202409981, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39037730

RESUMEN

Mediated electron transfer (MET) is fundamental to many biological functions, including cellular respiration, photosynthesis, and enzymatic catalysis. However, leveraging the MET process to enable the release of therapeutic gases has been largely unexplored. Herein, we report the bio-inspired activation of a series of UV-absorbing N-nitrosamide derivatives (NOA) under red light exposure, enabling the quantitative release of nitric oxide (NO) gasotransmitter via an MET process. The cornerstone of our design is the covalent linkage of a 2,4-dinitroaniline moiety, which acts as an electron mediator to the N-nitrosamide groups. This facilitates efficient electron transfer from the excited palladium(II) meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) photocatalyst and the selective activation of NOA. Our approach has been validated with distinct photocatalysts and various N-nitrosamides, including those derived from carbamates, amides, and ureas. Notably, the modulation of the linker length between the electron mediator and N-nitrosamide groups serves as a regulatory mechanism for controlling NO release kinetics. Moreover, this biomimetic NO release platform demonstrates effective operation under both normoxic and hypoxic conditions, and it enables localized delivery of NO under physiological conditions, exhibiting significant anticancer efficacy within the phototherapeutic window and enhanced selectivity towards tumor cells.


Asunto(s)
Luz , Óxido Nítrico , Óxido Nítrico/metabolismo , Óxido Nítrico/química , Transporte de Electrón , Humanos , Amidas/química , Catálisis , Estructura Molecular , Biomimética , Luz Roja
8.
Chemistry ; 30(56): e202401911, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39079912

RESUMEN

In the realm of biological macromolecules, entities such as nucleic acids and proteins are distinguished by their homochirality, consistently defined chain lengths, and integral sequence-dependent functionalities. Historically, these refined attributes have eluded traditional synthetic polymers, which often exhibit wide variabilities in chain lengths, limited batch-to-batch reproducibility, and stochastic monomer arrangements. Bridging this divide represents a pivotal challenge within the domain of polymer science - a challenge that the burgeoning discipline of precision polymer chemistry is poised to address. Recent advancements have yielded precision polymers that boast prescribed monomer sequences and narrow molecular weight distributions, heralding a new era for developing model systems to decipher structure-property correlations within functional polymers, analogous to those within biological matrices. This review discusses the innovative liquid-phase and solid-phase synthesis techniques for creating precision polymers and the advanced characterization tools essential for dissecting their structure and properties. We highlight potential applications in self-assembly, catalysis, data storage, imaging, and therapy, and provide insights into the future challenges and directions of precision polymers.

10.
Microorganisms ; 12(7)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39065179

RESUMEN

Habenaria and Liparis are well-known orchid genera that grow in terrestrial habitats in the tropics, subtropics or temperate zones. Three species have been found in subtropical regions of China, inhabiting terrestrial to epiphytic habitats. This study focuses on three species, H. dentata (distributed in Asia), H. yachangensis, and L. gigantea. For H. yachangensis and L. gigantea, there is no information about the mycorrhizal community in these species. This study aims to conduct the fungal community screening of Chinese ground orchids from subtropical regions. We performed a comparative analysis of the fungal community among H. dentata, H. yachangensis, and L. gigantea, determining their ITS regions using NGS paired-end sequences. The results clarified the diversity and the predominance of fungal genera. Ascomycota was abundant compared to Basidiomycota or other fungi groups in all communities, with a high dominance in all populations, especially for L. gigantea. At different root spatial locations, the fungal community diversity and richness were higher in the soil than in the rhizosphere or inner root. However, the results suggest that L. gigantea has a different fungal community compared to Habenaria species. In this order, the subtropical terrestrial orchids have a different fungal network compared to the northern terrestrial orchids. Also, there is a high probability of co-existence and co-evolution of endophytic fungi in these terrestrial orchids, indicating the potential role of host plants in selecting an endophytic fungal community. Furthermore, our results highlight the need to elucidate the microbe interactions of these unique orchids for long-term purposes, such as isolating indigenous fungi for suitable inoculants for further orchid propagation, restoration, and conservation.

11.
ACS Appl Mater Interfaces ; 16(20): 26348-26359, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38728664

RESUMEN

Organic solar cells (OSCs) could benefit from the ternary bulk heterojunction (BHJ), a method that allows for fine-tuning of light capture, cascade energy levels, and film shape, in order to increase their power conversion efficiency (PCE). In this work, the third components of PM6:Y6 and PM6:BTP-eC9 BHJs are a set of four star-shaped unfused ring electron acceptors (SSUFREAs), i.e., BD-IC, BFD-IC, BD-2FIC, and BFD-2FIC, that are facilely synthesized by direct C-H arylation. The four SSUFREAs all show complete complementary absorption with PM6, Y6, and BTP-eC9, which facilitates light harvesting and exciton collection. When BFD-2FIC is added as a third component, the PCEs of PM6:Y6 and PM6:BTP-eC9 binary BHJs are able to be improved from 15.31% to 16.85%, and from 16.23% to 17.23%, respectively, showing that BFD-2FIC is useful for most effective ternary OSCs in general, and increasing short circuit current (JSC) and better film morphology are two additional benefits. The ternary PM6:Y6:BFD-2FIC exhibits a 9.7% percentage of increase in PCE compared to the PM6:Y6 binary BHJ, which is one of the highest percentage increases among the reported ternary BHJs, showing the huge potential of BFD-2FIC for ternary BHJ OSCs.

12.
Angew Chem Int Ed Engl ; 63(24): e202405314, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38602843

RESUMEN

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5 M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

13.
Nat Commun ; 15(1): 3485, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664427

RESUMEN

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m-3 to 0.53 GPa and 700 MJ m-3, respectively. This is achieved by introducing ions to control the dissociation of polymer chains and evaporation-induced self-assembly under external stress. In addition, the artificial spider silk possesses thermally-driven supercontraction ability. This work provides inspiration for the design of high-performance fiber materials.


Asunto(s)
Nanofibras , Polielectrolitos , Seda , Arañas , Animales , Nanofibras/química , Arañas/química , Seda/química , Polielectrolitos/química , Resistencia a la Tracción , Músculos , Materiales Biomiméticos/química
14.
Molecules ; 29(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38474617

RESUMEN

Conjugated polymers (CPs) have attracted much attention in recent years due to their structural abundance and tunable energy bands. Compared with CP-based materials, the inorganic semiconductor TiO2 has the advantages of low cost, non-toxicity and high photocatalytic hydrogen production (PHP) performance. However, studies on polymeric-inorganic heterojunctions, composed of D-A type CPs and TiO2, for boosting the PHP efficiency are still rare. Herein, an elucidation that the photocatalytic hydrogen evolution activity can actually be improved by forming polymeric-inorganic heterojunctions TFl@TiO2, TS@TiO2 and TSO2@TiO2, facilely synthesized through efficient in situ direct C-H arylation polymerization, is given. The compatible energy levels between virgin TiO2 and polymeric semiconductors enable the resulting functionalized CP@TiO2 heterojunctions to exhibit a considerable photocatalytic hydrogen evolution rate (HER). Especially, the HER of TSO2@TiO2 heterojunction reaches up to 11,220 µmol g-1 h-1, approximately 5.47 and 1260 times higher than that of pristine TSO2 and TiO2 photocatalysts. The intrinsic merits of a donor-acceptor conjugated polymer and the interfacial interaction between CP and TiO2 account for the excellent PHP activity, facilitating the separation of photo-generated excitons. Considering the outstanding PHP behavior, our work discloses that the coupling of inorganic semiconductors and suitable D-A conjugated CPs would play significant roles in the photocatalysis community.

15.
Chem Sci ; 15(13): 4757-4762, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38550678

RESUMEN

α-Keto-, ß-acetoxy- and ß-amidoalkylsilyl peroxides are prepared from various precursors and utilized for Fe-catalyzed and visible-light-promoted radical functionalization with coupling partners under mild conditions with a broad substrate scope.

16.
Histol Histopathol ; 39(9): 1179-1195, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38293776

RESUMEN

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.


Asunto(s)
Displasia Cortical Focal , Malformaciones del Desarrollo Cortical de Grupo I , Proteínas del Tejido Nervioso , Semaforinas , Esclerosis Tuberosa , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Epilepsia Refractaria/metabolismo , Epilepsia Refractaria/patología , Epilepsia , Displasia Cortical Focal/metabolismo , Displasia Cortical Focal/patología , Células Gigantes/metabolismo , Células Gigantes/patología , Malformaciones del Desarrollo Cortical de Grupo I/metabolismo , Malformaciones del Desarrollo Cortical de Grupo I/patología , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Neuronas/metabolismo , Neuronas/patología , Semaforinas/metabolismo , Semaforinas/genética , Semaforinas/biosíntesis , Esclerosis Tuberosa/metabolismo , Esclerosis Tuberosa/patología
17.
Angew Chem Int Ed Engl ; 63(6): e202313370, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37875462

RESUMEN

Precise sequence-defined polymers (SDPs) with uniform chain-to-chain structure including chain length, unit sequence, and end functionalities represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for the bottom-up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable by other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non-destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting-edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.


Asunto(s)
Polímeros , Proteínas , Polímeros/química , Proteínas/química , Espectrometría de Masas en Tándem
18.
Macromol Rapid Commun ; 45(4): e2300566, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37931779

RESUMEN

Donor-acceptor (D-A) conjugated polymer (CP) featuring high charge mobility and widely tunable energy bands have shown promising prospects in photocatalysis. In this work, a library of ternary D-A CPs (22 polymers) based on benzothiadiazole, bithiophene, and fluorene derivatives (i.e., fluorene [Fl], 9,9-dihexylfluorene [HF], and 9,9'-spirobifluorene [SF]) with and without alkyl side chains, and with 3D geometry are designed and synthesized via atom-economical direct C-H arylation polymerization to explore the synergetic effects of stereochemistry, D/A ratio, and alkyl chains on the properties and photocatalytic performances, which reveal that 1) the cross-shaped 3D spirobifluorene (SF) building block shows the highest hydrogen evolution rates (HER) owing to the sufficient photocatalytic active sites exposed, 2) the alkyl-free linear polymer (FlBtBT0.05 ) exhibit the highest photocatalytic pollutant degradation performance owing to its superior charge separation, and 3) the alkyl side chains are redundances that will exert detrimental effects on the aqueous photocatalysis owing to their insulating and hydrophobic property. The structure-property-performance correlation results obtained will provide a desirable guideline for the rational design of CP-based photocatalysts.


Asunto(s)
Contaminantes Ambientales , Fluorenos , Hidrógeno , Polimerizacion , Polímeros
19.
Adv Mater ; 36(9): e2309315, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37944553

RESUMEN

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.


Asunto(s)
Neoplasias , Semicarbazonas , Humanos , Neoplasias/tratamiento farmacológico , Semicarbacidas , Péptidos , Microambiente Tumoral
20.
BMC Med ; 21(1): 500, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110931

RESUMEN

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.


Asunto(s)
Epilepsia , Esclerosis Tuberosa , Humanos , Fluorodesoxiglucosa F18 , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/metabolismo , Reproducibilidad de los Resultados , Glucólisis , Estudios Retrospectivos
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