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IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named "XGBoost.Enet-stacking-Enet" was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).
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Microdroplet chemistry is emerging as a great tool for accelerating reactions by several orders of magnitude. Several unique properties such as extreme pHs, interfacial electric fields (IEFs), and partial solvation have been reported to be responsible for the acceleration; however, which factor plays the key role remains elusive. Here, we performed quantum chemical calculations to explore the underlying mechanisms of an aza-Michael addition reaction between methylamine and acrylamide. We showed that the acceleration in methanol microdroplets results from the cumulative effects of several factors. The acidic surface of the microdroplet plays a dominating role, leading to a decrease of â¼9 kcal/mol in the activation barrier. We speculated that the dissociation of both methanol and trace water contributes to the surface acidity. An IEF of 0.1 V/Å can further decrease the barrier by â¼2 kcal/mol. Partial solvation has a negligible effect on lowering the activation barrier in microdroplets but can increase the collision frequency between reactants. With acidity revealed to be the major accelerating factor for methanol droplets, reactions on water microdroplets should have even higher rates because water is more acidic. Both theoretically and experimentally, we confirmed that water microdroplets significantly accelerate the aza-Michael reaction, achieving an acceleration factor that exceeds 107. This work elucidates the multifactorial influences on the microdroplet acceleration mechanism, and with such detailed mechanistic investigations, we anticipate that microdroplet chemistry will be an avenue rich in opportunities in the realm of green synthesis.
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Second near-infrared (NIR-II) optical imaging technology has emerged as a powerful tool for diagnostic and image-guided surgery due to its higher imaging contrast. However, a general strategy for efficiently designing NIR-II organic molecules is still lacking, because NIR-II dyes are usually difficult to synthesize, which has impeded the rapid development of NIR-II bioprobes. Herein, based on the theoretical calculations on 62 multiaryl-pyrrole (MAP) systems with spectra ranging from the visible to the NIR-II region, a continuous red shift of the spectra toward the NIR-II region could be achieved by adjusting the type and site of substituents on the MAPs. Two descriptors (ΔEgs and µgs) were identified as exhibiting strong correlations with the maximum absorption/emission wavelengths, and the descriptors could be used to predict the emission spectrum in the NIR-II region only if ΔEgs ≤ 2.5 eV and µgs ≤ 22.55 D. The experimental absorption and emission spectra of ten MAPs fully confirmed the theoretical predictions, and biological imaging in vivo of newly designed MAP23-BBT showed high spatial resolution in the NIR-II region in deep tissue angiography. More importantly, both descriptors of ΔEgs and µgs have shown general applicability to most of the reported donor-acceptor-donor-type non-MAP NIR-II dyes. These results have broad implications for the efficient design of NIR-II dyes.
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Recently, magnetically actuated micro/nanorobots hold extensive promises in biomedical applications due to their advantages of noninvasiveness, fuel-free operation, and programmable nature. While effectively promised in various fields such as targeted delivery, most past investigations are mainly displayed in magnetic control of individual micro/nanorobots. Facing practical medical use, the micro/nanorobots are required for the development of swarm control in a closed-loop control manner. This review outlines the recent developments in magnetic micro/nanorobot swarms, including their actuating fundamentals, designs, controls, and biomedical applications. The fundamental principles and interactions involved in the formation of magnetic micro/nanorobot swarms are discussed first. The recent advances in the design of artificial and biohybrid micro/nanorobot swarms, along with the control devices and methods used for swarm manipulation, are presented. Furthermore, biomedical applications that have the potential to achieve clinical application are introduced, such as imaging-guided therapy, targeted delivery, embolization, and biofilm eradication. By addressing the potential challenges discussed toward the end of this review, magnetic micro/nanorobot swarms hold promise for clinical treatments in the future.
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Robótica , Humanos , Robótica/instrumentação , Magnetismo , Desenho de Equipamento , Animais , Nanotecnologia/métodosRESUMO
Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.
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Glioblastoma , Glioma , Naftalenos , Piperazinas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Glioma/genética , Glioma/patologia , Fosforilação , Glioblastoma/patologia , Carcinogênese , Transformação Celular Neoplásica , Glucose , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Dendrobium nobile Lindl., as an endangered medicinal plant within the genus Dendrobium, is widely distributed in southwestern China and has important ecological and economic value. There are a variety of metabolites with pharmacological activity in D. nobile. The alkaloids and polysaccharides contained within D. nobile are very important active components, which mainly have antiviral, anti-tumor, and immunity improvement effects. However, the changes in the compounds and functional genes of D. nobile induced by methyl jasmonate (MeJA) are not clearly understood. In this study, the metabolome and transcriptome of D. nobile were analyzed after exposure to MeJA. A total of 377 differential metabolites were obtained through data analysis, of which 15 were related to polysaccharide pathways and 35 were related to terpenoids and alkaloids pathways. Additionally, the transcriptome sequencing results identified 3256 differentially expressed genes that were discovered in 11 groups. Compared with the control group, 1346 unigenes were differentially expressed in the samples treated with MeJA for 14 days (TF14). Moreover, the expression levels of differentially expressed genes were also significant at different growth and development stages. According to GO and KEGG annotations, 189 and 99 candidate genes were identified as being involved in terpenoid biosynthesis and polysaccharide biosynthesis, respectively. In addition, the co-expression analysis indicated that 238 and 313 transcription factors (TFs) may contribute to the regulation of terpenoid and polysaccharide biosynthesis, respectively. Through a heat map analysis, fourteen terpenoid synthetase genes, twenty-three cytochrome P450 oxidase genes, eight methyltransferase genes, and six aminotransferase genes were identified that may be related to dendrobine biosynthesis. Among them, one sesquiterpene synthase gene was found to be highly expressed after the treatment with MeJA and was positively correlated with the content of dendrobine. This study provides important and valuable metabolomics and transcriptomic information for the further understanding of D. nobile at the metabolic and molecular levels and provides candidate genes and possible intermediate compounds for the dendrobine biosynthesis pathway, which lays a certain foundation for further research on and application of Dendrobium.
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Alcaloides , Dendrobium , Transcriptoma , Dendrobium/genética , Dendrobium/metabolismo , Extratos Vegetais/metabolismo , Alcaloides/metabolismo , Terpenos/metabolismo , Metaboloma , Polissacarídeos/metabolismoRESUMO
Glioblastoma (GBM) progression is influenced by intratumoral heterogeneity. Emerging evidence has emphasized the pivotal role of extrachromosomal circular DNA (eccDNA) in accelerating tumor heterogeneity, particularly in GBM. However, the eccDNA landscape of GBM has not yet been elucidated. In this study, we first identified the eccDNA profiles in GBM and adjacent tissues using circle- and RNA-sequencing data from the same samples. A three-stage model was established based on eccDNA-carried genes that exhibited consistent upregulation and downregulation trends at the mRNA level. Combinations of machine learning algorithms and stacked ensemble models were used to improve the performance and robustness of the three-stage model. In stage 1, a total of 113 combinations of machine learning algorithms were constructed and validated in multiple external cohorts to accurately distinguish between low-grade glioma (LGG) and GBM in patients with glioma. The model with the highest area under the curve (AUC) across all cohorts was selected for interpretability analysis. In stage 2, a total of 101 combinations of machine learning algorithms were established and validated for prognostic prediction in patients with glioma. This prognostic model performed well in multiple glioma cohorts. Recurrent GBM is invariably associated with aggressive and refractory disease. Therefore, accurate prediction of recurrence risk is crucial for developing individualized treatment strategies, monitoring patient status, and improving clinical management. In stage 3, a large-scale GBM cohort (including primary and recurrent GBM samples) was used to fit the GBM recurrence prediction model. Multiple machine learning and stacked ensemble models were fitted to select the model with the best performance. Finally, a web tool was developed to facilitate the clinical application of the three-stage model.
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Rubidium-ion batteries (RIBs) have received a lot of attention in the quantum field because of their fast release and reversible advantages as alkali sources. However, the anode material of RIBs still follows graphite, whose layer spacing can greatly restrict the diffusion and storage capability of Rb-ions, posing a significant barrier to RIB development. Herein, using first-principles calculations, the potential performance of three kinds of in-plane porous graphene with pore sizes of 5.88 Å (HG588), 10.39 Å (HG1039), and 14.20 Å (HG1420) as anode materials for RIBs was explored. The results indicate that HG1039 appears to be an appropriate anode material for RIBs. HG1039 has excellent thermodynamic stability and a volume expansion of <25% during charge and discharge. The theoretical capacity of HG1039 is up to 1810 mA h g-1, which is â¼5 times higher than that of the existing graphite-based lithium-ion batteries. Importantly, not only HG1039 enables the diffusion of Rb-ions at the three-dimensional level but also the electrode-electrolyte interface formed by HG1039 and Rb-ß-Al2O3 facilitates the arrangement and transfer of Rb-ions. In addition, HG1039 is metallic, and its outstanding ionic conductivity (diffusion energy barrier of only 0.04 eV) and electronic conductivity indicates superior rate capability. These characteristics make HG1039 an appealing anode material for RIBs.
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Tricyclic antidepressant is an old and well-established therapeutic agent with a good safety profile, making them an excellent candidate for repurposing. In light of the growing understanding of the importance of nerves in the development and progression of cancer, attention is now being turned to using nerve-targeting drugs for the treatment of cancer, particularly TCAs. However, the specific mechanism by which antidepressants affect the tumor microenvironment of glioblastoma (GBM) is still unclear. Here, we combined bulk RNA sequencing, network pharmacology, single-cell sequencing, molecular docking and molecular dynamics simulation to explore the potential molecular mechanism of imipramine in the treatment of GBM. We first revealed that the imipramine treatment is presumed to target EGFRvIII and neuronal-derived EGFR, which may play a pivotal role in treating GBM by reducing the GABAergic synapse and vesicle-mediated release and other processes thereby modulating immune function. The novel pharmacological mechanisms might provide further research directions.
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Academician Tao Zhang from China and co-workers designed the first Pt1 /FeOx single-atom catalysts (SACs) in 2011, and they proposed the concept of "single-atom catalysis" in the field of heterogeneous catalysis. Generally, it is easy for active metal single-atom sites on a carrier to migrate and aggregate, which results in poor performance; or the chemical bond between the metal atom and carrier is too strong (immovable), which results in passivation of the active site. Recently, "nano-island" type SACs were designed, in which the active metal atoms are isolated on the "islands", and can move within the respective "island", but the migration across the "island" is blocked, to achieve a dynamic confinement design of single atoms (that is, a "moving but not aggregating" design philosophy). Herein, a new concept of "single-atom nano-islands (SANIs)" is proposed to describe these congeneric "atomic-nano" systems in heterogeneous catalysis fields. Particularly, the SANIs are divided into three categories: "one-island-one-atom", "one-island-multi-atoms", and "island-sea synergism" architectures. The scientific significance and application principles of SANIs in versatile heterogeneous catalysis fields (i.e., thermocatalysis, electrocatalysis, and photocatalysis) are summarized. The challenges and proposals of SANIs are also provided.
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The concept of "single-atom catalysis" is first proposed by Tao Zhang, Jun Li, and Jingyue Liu in 2011. Single-atom catalysts (SACs) have a very high catalytic activity and greatly improved atom utilization ratio. At present, SACs have become frontier materials in the field of catalysis. Aerogels are highly porous materials with extremely low density and extremely high porosity. These pores play a key role in determining their surface reactivity and mechanical stability. The alliance of SACs and aerogels can fully reflect their structural advantages and lead to new enhancement effects. Herein, a general concept of "atomic aerogel materials" (AAMs) (or single-atom aerogels (SAAs)) is proposed to describe this interesting new paradigm in both material and catalysis fields. Based on the basic units of "gel," the AAMs can be divided into two categories: carrier-level AAMs (with micro-, nano-, or sub-nanometer pore structures) and atomic-level AAMs (with atomic-defective or oxygen-bridged sub-nanopore structures). The basic unit of the former (i.e., single-atom-functionalized aerogels) is the carrier materials in nanostructures, and the latter (i.e., single-atom-built aerogels) is the single metal atoms in atomic structures. The atomic-defective or oxygen-bridged AAMs will be important development directions in versatile heterogeneous catalytic or noncatalytic fields. The design proposals, latent challenges, and coping strategies of this new "atomic nanosystem" in applications are pointed out as well.
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Hollow carbon nanocages (HCNCs) consisting of sp2 carbon shells featured by a hollow interior cavity with defective microchannels (or customized mesopores) across the carbon shells, high specific surface area, and tunable electronic structure, are quilt different from the other nanocarbons such as carbon nanotubes and graphene. These structural and morphological characteristics make HCNCs a new platform for advanced electrochemical energy storage and conversion. This review focuses on the controllable preparation, structural regulation, and modification of HCNCs, as well as their electrochemical functions and applications as energy storage materials and electrocatalytic conversion materials. The metal single atoms-functionalized structures and electrochemical properties of HCNCs are summarized systematically and deeply. The research challenges and trends are also envisaged for deepening and extending the study and application of this hollow carbon material. The development of multifunctional carbon-based composite nanocages provides a new idea and method for improving the energy density, power density, and volume performance of electrochemical energy storage and conversion devices.
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An organoboron small-molecular acceptor (OSMA) MBâN containing a boron-nitrogen coordination bond (BâN) exhibits good light absorption in organic solar cells (OSCs). In this work, based on MBâN, OSMA MB-N, with the incorporation of a boron-nitrogen covalent bond (B-N), was designed. We have systematically investigated the charge-transport properties and interfacial charge-transfer characteristics of MB-N, along with MBâN, using the density functional theory (DFT) and the time-dependent density functional theory (TD-DFT). Theoretical calculations show that MB-N can simultaneously boost the open-circuit voltage (from 0.78 V to 0.85 V) and the short-circuit current due to its high-lying lowest unoccupied molecular orbital and the reduced energy gap. Moreover, its large dipole shortens stacking and greatly enhances electron mobility by up to 5.91 × 10-3 cm2·V-1·s-1. Notably, the excellent interfacial properties of PTB7-Th/MB-N, owing to more charge transfer states generated through the direct excitation process and the intermolecular electric field mechanism, are expected to improve OSCs performance. Together with the excellent properties of MB-N, we demonstrate a new OSMA and develop a new organoboron building block with B-N units. The computations also shed light on the structure-property relationships and provide in-depth theoretical guidance for the application of organoboron photovoltaic materials.
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Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the ß-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.
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Glioma , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Proliferação de Células/genética , Movimento Celular/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular Tumoral , Glioma/genética , Glioma/patologia , Fatores de Transcrição/metabolismo , Fenótipo , Proteínas de Homeodomínio/metabolismo , Proteínas da Matriz Extracelular/metabolismoRESUMO
Cuproptosis, a newly discovered mechanism of programmed cell death, is important for detailing the metabolic aspects of cancer progression and thereby guiding cancer therapy. An exciting era of translational medicine has led to the rapid development of countless immunotherapeutic strategies. The existing successful cancer immunotherapies have sparked new hope for patients with solid and hematologic malignancies. Hence, it is important to characterize the link between the cuproptosis process and the immunity status in the tumor microenvironment (TME) in Lung Adenocarcinoma (LUAD), which may be able to predict patient's prognosis. In this study, we systematically assessed 10 cuproptosis-associated genes (CAGs) and comprehensively characterized the relationship between cuproptosis and the molecular characteristics and immune cell infiltration of tumor tissue, prognosis and clinical treatment of patients. Subsequently, the CAG_score for predicting overall survival (OS) was established and its reliable predictive ability in LUAD patients was confirmed. Next, we created a highly reliable nomogram to facilitate the clinical viability of the CAG_score. The low CAG_score group, with lower immune cell infiltration, and mutation burden, had a significantly superior OS, which was associated with a better response to immunotherapy. The present study revealed that cuproptosis play a significant role in TME regulation in LUAD. Collectively, we identified a prognostic CAGs-related signature for LUAD patients. This signature may contribute to clarifying the characteristics of TME and enable the exploration of more potent immunotherapy strategies.
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Secondary ion batteries rely on two-dimensional (2D) electrode materials with high energy density and outstanding rate capability. Rb- and Cs-ion batteries (RIBs and CIBs) are late-model batteries. Herein, using first-principles calculations, the potential performance of H-MoS2 as a 2D electrode candidate in RIBs and CIBs has been investigated. The M-top site on 2D H-MoS2 possesses the most stable metal atom binding sites, and after adsorbing Rb and Cs atoms, its Fermi level goes up to the conduction band, indicating a semiconductor-to-metal transition. The maximal theoretical capacities of RIBs and CIBs are 372.05 (comparable to those of commercial graphite-based LIBs) and 223.23 mA h g-1, respectively, due to the strong adsorption capability of H-MoS2 for Rb and Cs ions. Noticeably, the diffusion barriers of Rb and Cs on H-MoS2 are 0.037 and 0.036 eV, respectively. Such a low diffusion barrier gives MoS2-based RIBs and CIBs high rate capability. In addition, H-MoS2 also has the characteristics of suitable open-circuit voltage, low expansion, good cycle stability, low cost, and easy experimental realization. These results indicate that MoS2-based RIBs and CIBs are innovative batteries with great potential, and may provide opportunities for cross-application of energy storage and multiple disciplines.
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In recent years, some experiments and theoretical work have pointed out that diatomic catalysts not only retain the advantages of monoatomic catalysts, but also introduce a variety of interactions, which exceed the theoretical limit of catalytic performance and can be applied to many catalytic fields. Here, the interaction between adjacent metal atoms in diatomic catalysts is elaborated: synergistic effect, spacing enhancement effect (geometric effect), and electronic effect. With regard to the classification and characterization of various new diatomic catalysts, diatomic catalysts are classified into four categories: heteronuclear/homonuclear, with/without carbon carriers, and their characterization measures are introduced and explained in detail. In the aspect of preparation of diatomic catalysts, the widely used atomic layer deposition method, metal-organic framework derivative method, and simple ball milling method are introduced, with emphasis on the formation mechanism of diatomic catalysts. Finally, the effective control strategies of four diatomic catalysts and the key applications of diatomic catalysts in electrocatalysis, photocatalysis, thermal catalysis, and other catalytic fields are given.
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A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described. Following a Claisen rearrangement approach to construct the 6,9-bicycle, a transannular [2+2] photocycloaddition and the ensuing ring-opening reaction were implemented to forge the characteristic 5-6-8 propellane-like skeleton. Subsequent late-stage alkylations and reduction completed the synthesis.
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Compostos Policíclicos , Reação de Cicloadição , Cetonas , EstereoisomerismoRESUMO
The toxicity effects of paclitaxel (PTX)-loaded magnetic neutrophil-hybrid swimming microrobots ("neutrobots") in vivo were assessed after intravenous administration to mice. The mice after 72 hours exhibited minimal immunotoxicity and liver and kidney toxicity at an administration dose of 3 × 106 PTX-loaded neutrobots. The minor toxicity of drug-loaded neutrobots holds considerable promise for biomedical applications.
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Contenção de Riscos Biológicos , Paclitaxel , Animais , Camundongos , Paclitaxel/uso terapêuticoRESUMO
Molecular engineering has been demonstrated to be a predominant strategy for augmenting the long-term stability and passivating adverse defects for perovskite solar cells (PSCs). Here, using density functional theory calculations combined with ab initio molecular dynamics (AIMD) simulations, the passivation effects of bidentate passivation molecules, 2-MP and 2-MDEP, on the iodine vacancy MAPbI3 were comprehensively investigated. We demonstrate that 2-MDEP engenders stronger adsorption and localized charges on Pb atoms because the separated binding sites match with the MAPbI3 lattice. Moreover, the activation barriers for ion migrations are improved by the passivation of 2-MP and 2-MDEP. Furthermore, AIMD simulations verify the improved structural stability and restrained nonradiative recombination after passivation. More importantly, the durable Pb-heteroatom interactions at the interface and stronger hydrophobicity endow 2-MDEP with more remarkable shielding effects against moisture compared to those of 2-MP. This work deepens our understanding of the passivation effects and paves the way for the design of passivation molecules toward the attainment of efficient and stable PSCs.