This study presents a bibliometric analysis of research on noninvasive nanoparticle drug delivery systems for the transocular surface from 2004 to 2023. Relevant publications were retrieved from the Web of Science Core Collection. VOSviewer and CiteSpace were used to map contributions by countries/regions, authors, institutions, journals, keywords, keyword clusters, and timeline trends. A total of 695 articles were analyzed, showing a steady year-by-year increase in publications. China, the United States, and Spain were the leading contributors. Among authors, Alvarez-Lorenzo, Carmen was the most prolific, while Chanhan, Anuj's work received the most citations among the top 10 prolific researchers. The International Journal of Pharmaceutics published the highest number of articles in this field, whereas the Journal of Controlled Release was the most frequently cited among the top 10 most productive journals. The University of Santiago de Compostela and the University of Florida were among the most active institutions in this research area. Keyword analysis identified recent key themes such as controlled release, cell interaction, dry eye, mechanisms, gene expression, and ocular drug delivery. The growing interest in transocular surface nanoparticle drugs is driven by their advantages, including increased solubility, improved stability, reduced administration frequency, sustained therapeutic concentrations, enhanced corneal penetration, and prolonged ocular surface residence time.

Integrating single-cell datasets from multiple studies provides a cost-effective way to build comprehensive cell atlases, granting deeper insights into cellular characteristics across diverse biological systems. However, current data integration methods struggle with interference in partially overlapping datasets and varying annotation granularities. Here, a multiselective adversarial network is introduced for the first time and present UniMap, which functions as a "discerner" to identify and exclude interfering cells from various data sources during dataset integration. Compared to other state-of-the-art methods, UniMap emphasizes type-level integration and proves to be the best model for preserving biological variability, achieving noticeably higher accuracy in single-cell automated annotation under various circumstances. Additionally, it enhances interpretability by revealing shared and domain-specific cell types and providing prediction confidence. The efficacy of UniMap is demonstrated in terms of identifying new cell types, creating high-resolution cell atlases, annotating cells along developmental trajectories, and performing cross-species analysis, underscoring its potential as a robust tool for single-cell research.

Nano MgO and light-burnt MgO were added into pastes mixed with Portland cement and slag to compensate for the shrinkage of mass concrete. The results indicated that an increased nano MgO content improved strength within a certain range. The strength of group with 8 % nano MgO increased by 12 % and 8 % under autoclaving and water curing, respectively, while increased light-burned MgO content deteriorated strength. The nano MgObased group exhibited enhanced compressive strength and smaller expansion than the light-burnt MgO-based group, due to its higher efficiency of filling pores by uniformly distributed brucite. Moreover, MgO hydration mainly occurred within 365 d of water curing, and nano MgO and light-burnt MgO were fully hydrated at 730 d. Overall, this study provided the theoretical basis for adding nano-MgO and light-burnt MgO to compensate for the shrinkages of mass concrete on a large scale.

9-aminacrine (9-AA), an external antibacterial agent, possesses important bioactivities for the treatment of cancer, viruses, and prion diseases. Recent research has revealed that 9-AA has anti-inflammatory effects through the up-regulation of nuclear receptor subfamily 4 group A member 1 (NR4A1), but it is highly cytotoxic. To mitigate its toxicity, three series of novel 9-AA derivatives were synthesized. The toxicity of all compounds was assessed, and some of the less toxic compounds were tested for in vitro anti-inflammatory activities, leading to the establishment of structure-activity relationships. In particular, 9-amino-8-bromo-3,4-dihydroacridin-1(2H)-one exhibited relatively low toxicity and retained anti-inflammatory activity, with a higher selectivity index compared to 9-AA (3.44 versus 0.68). Expression experiments of inflammatory mediators revealed that this compound not only inhibited the gene expression of pro-inflammatory factors, but also promoted the gene expression of anti-inflammatory factors. Preliminary mechanistic studies suggested that it exerted anti-inflammatory effects through the NR4A1/Interleukin-10 (IL-10)/suppressors of cytokine signalling 3 (SOCS3) signaling pathway. Furthermore, molecular docking studies indicating that it may exhibit anti-inflammatory activity by inhibiting the protein targets phosphodiesterase-4 (PDE-4) and p38 mitogen-activated protein kinases (MAPK). Based on our data, 9-amino-8-bromo-3,4-dihydroacridin-1(2H)-one with its low toxicity and anti-inflammatory properties, holds promise for further development as an anti-inflammatory agent.

The facile synthetic approach of coumarin derivatives has been described through Michael addition/cyclization/oxidative benzannulation using carbon-based solid sulfonic acid as the sustainable catalyst. The reaction proceeds in good to excellent yields in one-step from hydroxy-substituted chalcone, ethyl acetoacetate and amine. The utility of this transformation has been highlighted by its use for the construction of alkylaminobenzocoumarin, which was a new coumarin fluorescent molecular.

AbstractA copper-catalyzed, three-component, one-pot, 1,3-dipole cycloaddition/oxidation has been developed to construct pyrrolo[2,1-a]isoquinolinoquinone derivatives, with environmentally friendly oxygen as the oxidant. The pyrrolo[2,1-a]isoquinolinoquinone products were obtained from naturally available tetrahydroisoquinolines, 1,4-naphthoquinones, and benzaldehydes in medium yields.

A series of new 3-(indol-3-yl)-4-(pyrazolo[3,4-c]pyridazin-3-yl)-maleimides were synthesized and evaluated for their inhibitory activity against IDH1-R132H. Most compounds exhibited significant potency to IDH1-R132H inhibition. Among these, 3-(1-(3-(1H-imidazol-1-yl)propyl)-6-bromo-1H-indol-3-yl)-4-(1-methyl-1H-pyrazolo[3,4-c]pyridazin-3-yl)-1H-pyrrole-2,5-dione (compound IXb), was the most promising IDH1-R132H inhibitor (IC50 = 0.031 μM) and could significantly inhibit the production of 2-HG in U87MG IDH1-R132H cells. Preliminary structure–activity relationships and molecular modeling studies are discussed based on the experimental data obtained.

A series of novel 3-(indol-3-yl)-4-(pyrazolo[3,4-c]pyridazin-3-yl)maleimides were synthesized and evaluated for their inhibitory activity against mutant isocitrate dehydrogenase-1 (R132H). Most compounds exhibited potent potency to IDH1-R132H. Among them, compound 9b was the most promising IDH1-R132H inhibitor with IC50 values of 31 nmol/L and could significantly inhibit the production of 2-HG in human brain astroblastoma cells with mutant isocitrate dehydrogenase-1 (R132H). Preliminary structure-activity relationship and molecular modeling studies were discussed based on the experimental data obtained.

3-Chloro-4-indolylmaleimides and two different alkynes are used as the starting materials in a novel and highly effective Pd-catalyzed addition/C–H activation/cyclization sequence for the synthesis of pyrrolo[3,4- c]carbazole-1,3(2 H,6 H)-diones. The desired products are obtained in moderate to excellent yields. Such compounds show a wide range of biological activities.

A series of novel linear and V-shaped carbazole-based molecules functionalized by cyano acceptors and diversified donors (carbazole, diphenylamino, dimethylamino, methoxy, and ferrocene) were synthesized and characterized by hydrogen-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Their linear and nonlinear optical properties including UV-visible absorption, single-photon excited fluorescence, two-photon absorption, and frequency up-converted fluorescence, were systematically investigated in various solvents. The time-resolved photoluminescence studies using time-correlated single photon counting revealed their fluorescence lifetimes in THF. The solvent polarity exerts little effect on their absorption properties, while the emission properties (maximum fluorescence wavelength, Stokes shift, fluorescence quantum yield) display solvent polarity dependencies. Donor-acceptor functionalities and molecular dimensionality are considered to be the crucial structural factors that influence their optical properties. Pumped by a femtosecond laser (690-990 nm, 80 MHz, 140 fs), all the target molecules emit intense frequency up-converted fluorescence except FC1 and FC2 which contain one or two ferrocene donors. The two-photon absorption cross-sections in THE are in the range of 631-3014 GM. The density functional theory calculations were also conducted to unravel their electronic structures and to further understand the structure-property relationships. To our knowledge, this study is the first to be concerned with the single- and two-photon related photophysical properties of these D-pi-A-pi-D' and D'-pi-A-pi-D-pi-A-pi-D' carbazole-based molecules (D = donor, A = acceptor, pi = conjugated bridge).

A simple and highly efficient method for the preparation of tetrasubstituted NH-pyrrole from a wide range of chalcones and diethyl iminodiacetates via a Cu(OAc)(2)-promoted oxidation/[3+2]cycloaddition/aromatization cascade reaction has been developed. This reaction proceeds through dehydrogenations, deamination, and oxidative cyclization, affording the corresponding products in good to excellent yields. This convenient methodology for constructing tetrasubstituted NH-pyrroles has several advantages over existing methods, such as the use of easily accessible chalcones and readily available diethyl iminodiacetates, and mild reaction conditions. A wide range of substrates are tolerated.

A novel one-pot 1,3-dipolar cycloaddition/oxidation reaction of 1,4-quinones, aromatic aldehydes, and N-substituted amino esters to construct polysubstituted benzo[f]isoindole-4,9-diones induced by benzoic acid is reported. Based on optimized reaction conditions, various polysubstituted benzo[f]isoindole-4,9-diones derivatives are obtained in moderate yields. This straightforward methodology employs mild reaction conditions, a green oxidant, and readily available starting materials. Notably, a wide range of substrates is tolerated.

A set of NF-κB-inducing kinase (NIK) inhibitors was used to develop a molecular docking-based QSAR model by using nonlinear regression method. The accuracy of the QSAR model was remarkably improved by integrating the docking scores and key interaction profiles. Two indole-aminopyrimidine derivatives 32a and 32b predicted as NIK inhibitors were synthesized and biologically evaluated. The significant correlationship between experimental data and MD-SVR model-predicted results were observed. The binding mode of 32a and 32b with NIK were further investigated by dynamic simulations. Compound 32b was proposed as a promising lead for the findings of highly potent inhibitors.

Selective ratiometric fluorescent sensor b for detection of silver ions and its counterparts (sensor a and c) were efficiently synthesized based on 3-indolyl-4-indazolyl maleimide, and their photophysical properties and activities towards metal ions were examined. The experimental results were verified by density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. The results demonstrated that sensor b could selectively and sensitively recognize Ag+ compared with other competing metal ions in tetrahydrofuran (THF). It probably forms a 1:1 complex with Ag+, displaying a 52-nm bathochromic shift of the fluorescence emission spectrum. Moreover, the binding mechanism was investigated using binding stoichiometry titration and 1H, 13C nuclear magnetic resonance (NMR).

A series of 3-aryl-4-indolylmaleimide IDH1/R132H inhibitors with a novel structure was obtained by high-throughput screening and structure-based optimization. Most compounds such as 7a, 7d, 7h, 7i, 7k and 7o showed high inhibitory effects on IDH1/R132H and were highly selective against IDH1/WT, IDH2/WT, GDH, GK, and FBP. Evaluation of the biological activities and function at cellular level showed that compounds 7h, 7i and 7k could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Additionally, 7h could reversed the differentiation block of the myeloid leukemic cell line, TF-1, caused by the overexpression of IDH1/R132H. We also explore the structure-activity relationship based on the experimental data, with an attempt to pave the way for future studies.

针对月球真空环境和其富含火山灰质材料的特点,对经干混蒸压养护制得的水泥硬化体的性能随凝灰岩微粉掺量的变化规律进行了研究.结果表明:其抗压强度随凝灰岩微粉掺量的增加呈先提高后逐渐降低,在凝灰岩微粉掺量相同的条件下,干混蒸压养护的硬化浆体抗压强度高于经湿拌蒸压养护后的硬化浆体强度,且明显高于经湿拌标准养护28 d的硬化浆体强度,在其硬化浆体中,水泥熟料矿物已水化;在凝灰岩微粉掺量大于20％时,氢氧化钙晶体已不存在;随着凝灰岩微粉掺量的增加,依次出现的水化硅酸钙的产物为水化硅酸三钙、水化硅酸二钙、硬硅钙石、托勃莫来石和白钙沸石.

Biological CO2 elimination by photosynthetic microalgae is a sustainable way to mitigate CO2 from flue gas and other sources. Computational fluid dynamics was used to simulate algal cell movement with an enhanced flashing light effect in a novel panel bioreactor with horizontal baffles. Calculation results showed that the light/dark (L/D) cycle period decreased by 17.5% from 17.1 s to 14.1 s and that the horizontal fluid velocity increased by 95% while horizontal baffles were used under a 0.02 vvm air aeration rate and a microalgal concentration of 0.85 g L-1. The probability of the L/D cycle period within 5-10 s increased from 27.9% to 43.6%, indicating a 56% increase when horizontal baffles existed. It was proved by experiments that the mass-transfer coefficient increased by 31% and the mixing time decreased by 13% under a 0.06 vvm air aeration rate when horizontal baffles were used, and the algal biomass yield increased by ∼51% along with the decrease in the L/D cycle period when horizontal baffles were used.

A series of 3-(7-azainodyl)-4-indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild-type IDH1. Evaluation of the biological activities at the cellular level showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Preliminary structure-activity relationship (SAR) and molecular modeling studies were discussed based on the experimental data obtained. These findings may provide new insights into the development of novel IDH1/R132H inhibitors.

A range of 3-indolyl-4-indazolyl maleimide fluorescent compounds, including 2a, 2b, 2c, 3a and 3b, were synthesized efficiently. In different organic dissolvents, the photo-physical performance was checked, either in the aggregated state or in the solid state. When being in solid and in solution state, these fluorescent compounds showed high fluorescent intensity, indicating a highest fluorescence quantum efficiency of 45% accompanying a large Stokes Shift longer than 100 nm in toluene. Also, they can carry out a phenomenon of aggregation -induced emission enhancement (AIEE). TDDFT and OFT calculations were used to confirm the experimental findings. (C) 2017 Elsevier Ltd. All rights reserved.

A series of novel 4,5-bisindolyl-1,2,4-triazol-3-ones were designed, prepared and evaluated for their glycogen synthase kinase (GSK)-3β inhibitory activities. Compounds exhibited favorable inhibitory potency towards GSK-3β kinase at the molecular level and in cells indicated by significantly reducing GSK-3β substrate Tau phosphorylation at Ser396 in primary neurons showing the inhibition of cellular GSK-3β. In an in vitro model of neuronal injury, compounds 6b, 6d and 6f prevented glutamate-induced neuronal death which was closely associated with cerebral ischemic stroke. Preliminary structure-activity relationship was examined and showed that different substituents on the indole ring had significant influences on the GSK-3β inhibitory potency. These findings may provide new insights into the development of novel GSK-3β inhibitors as neuroprotective agents.