Search Results (12,502)

Using satellite observations and computed variables, we specified 5 Subauroral Polarization Stream (SAPS) and 28 Subauroral Ion Drift (SAID) events observed in the Northern Hemisphere by spacecraft F18 in 2013. These SAPS-SAID flows reached supersonic velocities (2400–5200 m/s), were driven by westward E × B ion drifts generated by their underlying strong poleward meridional SAPS-SAID electric (E) fields (90–190 mV/m) and northward geomagnetic B fields, and developed at high (≥68°) magnetic latitudes, in the dusk sector, sometimes on the dayside, and mostly within the downward region-2 current suggesting their previous development. Within the deepening main trough, the poleward SAPS/SAID E field increased directly with the reductions in plasma density and conductivity, suggesting positive feedback mechanisms in progress. Across the highly inclined magnetic field lines within the subauroral flow channel, the eastward/westward zonal E field E × B drifted ions equatorward/poleward and yielded large upward/downward ion drifts observed by F18. Earthward energy deposition into the SAPS and SAID channels indicates magnetospheric electromagnetic energy generations in their respective voltage generators. Conjugate observations depict the large outward SAID E field (|E_X ≈ 10 mV/m|) on 28 October 2013 and SAPS E field (|E_Z ≈ 10 mV/m|) on 14 October 2013 developed at L ≈ 10 R_E on a short timescale at dusk. Full article

[¹¹¹In]In-diethylenetriaminepentaacetic acid-5,10,15,20-tetraphenylporphyrin ([¹¹¹In]In-DTPA-TPP) nanodroplets were developed for cancer theranostics, featuring ultrasound-sensitive properties. The designed nanodroplets that encapsulate the low-boiling-point liquid perfluorocarbon and IR-780 iodide, a near-infrared fluorescent dye, with surface conjugation of ¹¹¹In-labeled porphyrin derivative, were synthesized and evaluated by in vitro and in vivo experiments. The cellular uptake of [¹¹¹In]In-DTPA-TPP nanodroplets was significantly higher than that of control nanodroplets without TPP. Biodistribution experiments revealed greater tumor accumulation in mice injected with [¹¹¹In]In-DTPA-TPP nanodroplets than in those injected with control nanodroplets lacking TPP. Additionally, the accumulation of [¹¹¹In]In-DTPA-TPP nanodroplets in the tumor was visualized by single-photon emission computed tomography. Sonodynamic therapeutic experiments revealed that DTPA-TPP nanodroplets at 10 µmol total lipids/kg weight with a single ultrasound irradiation onto the tumor area significantly inhibited tumor growth. These results indicate that [¹¹¹In]In-DTPA-TPP nanodroplets would be promising cancer theranostic agents. Full article

HER2-low breast cancer, also known as IHC 1+ or IHC 2+ without ERBB2 amplification, is a new concept in the biology of breast cancer that has removed the binary classification of HER2-positive or HER2-negative breast cancer. The recent introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), has improved therapeutic outcomes for HER2-low breast cancer by demonstrating high efficacy in HER2-low tumors through efficient payload delivery. However, differences in ADC efficacy exist among HER2-low breast cancer patients, with tumor cells showing resistance to ADCs. Recent research indicates that the tumor microenvironment (TME) plays a critical role in determining the efficacy of ADCs against tumor cells. TME creates a barrier to the delivery of ADCs to tumor cells that show resistance to ADCs. This review article aims to highlight the current understanding of the biology of HER2-low breast cancer and its response to ADCs with reference to the tumor microenvironment. Full article

To develop high-performance iridium phosphorescent complexes, we designed and synthesized a series of iridium phosphorescent complexes (G-1, G-2, B-1, B-2, R-1, R-2) using 3-hydroxy-2-methyl-4-pyrone (maltol, short for mal) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol, short for emal) as auxiliary ligands, in combination with 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (dfppy), and 1-phenylisoquinoline (piq) as cyclometalating ligands. We systematically investigated their crystal structures, photophysical behavior, electrochemical properties, and electroluminescent performance. The results revealed that the combination of a pyranone auxiliary ligand with the highly conjugated piq ligand leads to the formation of R-1 and R-2, which possess high molecular symmetry and display favorable photophysical performance. These complexes exhibit solution-phase phosphorescence quantum yields of 64% and 55%, and electroluminescent devices incorporating them reach a maximum external quantum efficiency of 13.4%, with brightness exceeding 13,000 cd/m² and minimal efficiency roll-off. In contrast, complexes incorporating pyridine-based cyclometalating ligands (ppy, dfppy)—G-1, G-2, B-1, and B-2—display weak emission in solution but show enhanced solid-state emission through π–π stacking, with a maximum quantum yield of 25.8%. Density functional theory calculations and electrochemical analysis indicate that the presence of both the pyranone auxiliary ligand and the piq ligand results in optimized frontier orbital energy alignment, enhanced metal-to-ligand charge transfer, and reduced non-radiative transitions, thereby improving emission efficiency. This study provides a theoretical framework and molecular design strategy for the application of pyranone auxiliary ligands in high-performance iridium phosphorescent materials. Full article

siRNA, as a precise, specific, and highly effective gene-silencing therapy, has been extensively studied. Before reaching tumor cell targets, siRNA formulations must overcome multiple extracellular barriers, including clearance from the bloodstream, membrane impermeability, capture by the mononuclear phagocyte system (MPS), rapid renal excretion, endosomal escape, and precise recognition of target cells. These challenges limit siRNA’s clinical application. Consequently, various modifications have been applied to siRNA to enhance transfection efficiency, while researchers continue to pursue improved siRNA-targeting delivery systems. Nanotechnology offers a rational technical approach to address siRNA delivery. Nanoparticles can increase transfection efficiency while exhibiting lower cytotoxicity and reduced off-target effects. Various matrices have been employed to construct nanoparticles for targeted therapeutic delivery. This review briefly discusses siRNA nanoparticle delivery strategies, illustrates examples of various siRNA nanodelivery systems, such as lipid nanoparticles, polymeric siRNA nanoparticles, inorganic nanoparticles, hybrid nanoparticles, and conjugate-siRNA delivery systems, and introduces clinical trials of siRNA-loaded nanoparticles for cancer treatment, which can provide valuable references for further research and clinical application of siRNA nanoparticle delivery systems. Full article

Severe browning often occurs in Multivitamin Iron Oral Solution during storage, which directly leads to the decline of product quality. To clarify the main mechanism of browning in this preparation, the contents of 5-hydroxymethylfurfural (5-HMF) and carbohydrates, as well as the relevant characteristic parameters such as color and fluorescence, were determined at different storage times in this study. Subsequently, four reaction models, namely sucrose-lysine, sucrose-citric acid, sucrose-niacin, and sucrose-folic acid, were constructed according to the formulation of the preparation to systematically investigate the effects of each system on browning. The results showed that the sucrose-lysine model was the main color-forming reaction system of the preparation. Citric acid could significantly promote the hydrolysis of sucrose to produce two reducing sugars, glucose and fructose, which not only provided sufficient substrates for the Maillard reaction (MR), but also led to the massive accumulation of 5-HMF. Further analysis revealed that heating temperature and heating time were significantly positively correlated with the contents of 5-HMF, browning index (BI), color density (CD), and reducing sugars in the solution, while significantly negatively correlated with sucrose content (p < 0.05). Two fractions, P1 and P2, were isolated by Sephadex LH-20 column chromatography. Among them, P1 with a molecular weight of 61,660 Da was identified as the key fluorescent color-forming component, whose ultraviolet and fluorescence characteristics were basically consistent with those of Multivitamin Iron Oral Solution. Ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) analysis confirmed that P1 contained characteristic fragments of conjugated unsaturated structure, which was the key chromophore responsible for its fluorescence properties. In summary, this study explored the main browning mechanism of Multivitamin Iron Oral Solution. It was found that after citric acid catalyzed the hydrolysis of sucrose, the generated reducing sugars underwent Maillard reaction with lysine to produce fluorescent color-forming substances, and heat treatment significantly aggravated the browning process. The results of this study not only provide a solid theoretical basis for optimizing the preparation process and improving the storage stability of Multivitamin Iron Oral Solution, but also offer an important reference for the research on the browning mechanism and stability of other sugar-containing liquid preparations. Full article

Coal-bed gas well production is too low to realize a highly efficient exploitation of the #8 coal seam in the Shanxi formation in the Nalin region. Based on the reservoir characteristics, the designed poly-aromatic-grafted silicon-quantum-dot-based desorption agent (PQS) has been developed. Then, the adsorption/desorption behavior of CBM on the coal surface under the influence of this active chemical has been studied, and the synergy effect with an anionic–nonionic surfactant to desorption of CBM has also been discussed. The results show that the developed poly-aromatic-grafted silicon quantum dot, with a median size of 4.9 nm and +5.6 mV of zeta potential in neutral condition, has a significant emission peak with 470 nm at the excitation of 380 nm and 150,000 mg/L of salinity resistance, which also generates a strong adsorption capacity on the coal surface. A promoting effect to desorption of CBM for PQS nanofluid is exhibited and the Langmuir pressure is obviously increased. However, when the PQS nanofluid is synergized with an anionic–nonionic surfactant, the desorption of CBM is further improved and the wettability of the coal surface is altered from 78.2° to 84.2°. The desorption rate for this compound system reached 65.3%. It can be found that combining the quantum size, π–π stacking, π–π conjugation, and the synergy effect between PQS nanofluid and surfactant fluid with the traditional intermolecular force has a stronger capacity for promoting desorption of CBM than the conventional desorption agent. This study provides guidance for the molecular design of the desorption agent for deep coal rock and the application of silicon quantum dots. Full article

This study explores the sustainable extraction, quantification, and functional evaluation of antioxidant amphiphilic (TAC) and lipophilic (TLC) compounds from avocado (Persea americana) products and by-products using green, solvent-efficient extraction, for potential applications in functional foods and/or cosmetics. Juice derived from organically grown domestic (Greek) avocado and the remaining juicing pulp by-products were subjected to a green extraction and partitioning fractionation process to obtain separately the extracted TLC and TAC. Quantitative analyses of total phenolic (TPC) and carotenoid contents (TCC), as well as antioxidant activity (DPPH, ABTS, FRAP), were performed using UV–Vis spectroscopy just after the extraction. ATR–FTIR spectroscopy was used to structurally characterize TAC bioactives compared to standards (gallic acid, quercetin, beta-carotene, soy phospholipids). TAC extracts exhibited higher TPC and superior antioxidant capacity across all assays, in comparison to the TLC, especially in the by-products. Despite relatively modest absolute phenolic and carotenoid concentrations compared to the literature, the extracts retained potent bioactivity, indicating selective enrichment of functional compounds. UV–Vis spectral peaks (240 nm, 310 nm) confirmed the presence of conjugated systems, suggesting potential for anti-UV photo-protective cosmetic applications. ATR–FTIR analysis further identified functional groups of key amphiphilic constituents, including simple phenolics, flavonoids, polyphenols, carotenoids and polar lipids. TAC extracts were successfully integrated into plant-based jelly prototypes as functional food supplements. Antioxidant stability of the jelly was retained for 15 days under refrigeration, though shelf-life limitations due to moisture and microbial growth highlight the need for preservative strategies. This work demonstrates a circular bioeconomy approach to food waste valorization, with significant implications for sustainable innovation in functional foods and clean-label cosmetics. Full article

In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) and the fibrotic stroma generate form a dense stromal barrier that restricts the intratumoural exposure and spatial distribution of oxaliplatin. To enable local stromal remodelling of this pathological stromal compartment, we selected fibroblast activation protein (FAP) as a stromal target and co-assembled two amphiphilic conjugates, oncoFAP and retinoic acid (RA), into an FAP-directed RA nanoformulation termed LRA^FAP. LRA^FAP exhibited a uniform size distribution (107.1 ± 5.8 nm), remained stable for at least 7 d at 37 °C in PBS or serum-containing PBS, and showed accelerated esterase-responsive release. In a TGF-β-induced CAF-like model, LRA^FAP markedly suppressed the expression of CAF activation-associated markers, reducing Fap and Acta2 mRNA levels by approximately 70% and 60%, respectively. In vivo, LRA^FAP showed enhanced accumulation in CAF-enriched tumours and an increase in intratumoural oxaliplatin levels of approximately 2.5-fold relative to oxaliplatin alone. LRA^FAP also reduced collagen deposition and CAF activation markers, and enhanced the antitumour efficacy of oxaliplatin while maintaining good tolerability. Collectively, these findings indicate that LRA^FAP promotes local stromal remodelling and improves intratumoural oxaliplatin exposure, thereby enhancing the efficacy of oxaliplatin-based chemotherapy in CRC. Full article

Gonad loss triggers severe endocrine disorders and altered energy metabolism, yet the precise mechanisms remain poorly understood. In swine production, surgical castration is widely performed to eliminate boar taint and aggressive behavior, but it impairs feed efficiency, increases fat deposition, and raises animal welfare issues. Castration reduces testosterone and estrogen levels, leading to elevated gonadotropin-releasing hormone (GnRH) and its downstream follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Traditionally viewed as a reproductive hormone, FSH has recently emerged as a critical regulator of peripheral metabolism. Based on these findings, we designed and developed a novel FSH vaccine comprising an FSHβ13AA-tandem-ovalbumin conjugate, which has been demonstrated to effectively regulate growth and metabolism in castrated boars. In conclusion, this review underscores the previously underrecognized metabolic functions of follicle-stimulating hormone (FSH) and proposes a novel immunomodulatory strategy targeting FSH for fine-tuning organ function and energy metabolism. This approach shows considerable potential for advancing sustainable, welfare-oriented swine production. Full article

Background/Objectives: The neonatal Fc receptor (FcRn) plays a crucial role in extending the systemic half-life of monoclonal antibodies (mAbs), but its influence on ocular distribution remains incompletely understood. This study investigated the impact of FcRn on the ocular disposition of mAbs following systemic administration in rabbits. Methods: New Zealand White rabbits received a single intravenous dose (1 mg/kg) of either wild-type trastuzumab (TS-WT) or its FcRn non-binding variant (IHH). Plasma and ocular tissues (retina, iris–ciliary body, vitreous humor, aqueous humor, cornea, conjunctiva, and tears) were collected at terminal time points up to 336 h for TS-WT and 168 h for IHH. Antibody concentrations were quantified using a validated sandwich ELISA. Pharmacokinetic parameters and antibody biodistribution coefficients (ABC) were calculated to assess the FcRn-mediated effects on ocular distribution. Results: TS-WT demonstrated 2-fold higher systemic exposure compared to IHH. The iris–ciliary body exhibited the highest absolute exposure for both antibodies, with TS-WT showing significantly higher accumulation (ABC_0–168h: 14.95% vs. 8.89%). Retinal distribution remained comparable between antibodies (5.96% vs. 5.51%). Both antibodies were detectable in tears, with ABC value of ~4% reported for TS-WT. TS-WT also demonstrated markedly increased distribution in vitreous humor and tear fluid (3.5- and 5.5-fold higher ABC values, respectively) compared to IHH. The cornea (5.76% vs. 5.57%) and conjunctiva (7.71% vs. 7.21%) showed comparable relative distribution between TS-WT and IHH, while aqueous humor showed minimal differences (0.44% vs. 0.52%). Conclusions: This investigation reveals distinct tissue-specific patterns of FcRn-mediated mAb distribution within the eye. FcRn binding significantly enhanced antibody distribution in ocular tissues, such as the iris–ciliary body, and tears, with less pronounced effects on the retina, cornea, conjunctiva and aqueous humor. These findings provide mechanistic insights for optimizing mAb-based therapeutics for ocular disease and understanding the ocular toxicity of mAb-based therapeutics, such as antibody–drug conjugates. Full article

Background/Objectives: Mass spectrometry-based multi-attribute methods (MAM) have the potential to transform therapeutic protein analysis by enabling comprehensive monitoring of multiple quality attributes in a single assay. However, the widespread adoption of MAM is hindered by significant challenges, most notably artificial oxidation during sample preparation and analysis. This report summarizes long-term operational observations and several case studies that substantiate this concern. Methods: A tryptic digest, high-resolution LC-MS MAM workflow was applied to an Fc-fusion protein and multiple antibody-based therapeutics, with a frozen reference standard analyzed in each run for system suitability and longitudinal trending. Oxidation excursions were investigated by comparing laboratories, consumables, LC-MS configurations, and other method parameters. Results: In a seven-year trending record, apparent total methionine oxidation in the Fc-fusion protein reference standard showed an abrupt, sustained increase (up to ~5-fold); the shift was traced to a specific bag of microcentrifuge-tubes used during buffer exchange and resolved after those tubes were discontinued. In an antibody–drug conjugate, observed methionine oxidation was strongly influenced by the sample preparation procedure. In other antibodies, variability of observed methionine oxidation was attributed to on-column oxidation, which produced a broad and noisy peak that interferes with automated peak integration. EDTA flushing reduced this feature, implicating exposure to metal ions. Conclusions: While advances continue to address many MAM challenges, artificial oxidation remains unpredictable and constitutes a major obstacle to robust implementation in regulated QC environments. Enhanced control strategies and further research are urgently needed to ensure reliable therapeutic protein analysis. Such control strategies include consumable qualification and change control, system suitability/trending using a reference standard, metal management across LC flow path/column lifecycle, reduction of trifluoracetic acid (TFA) exposure, data analysis to safeguard excessive on-column oxidation, etc. Full article

The diamondback moth (Plutella xylostella) severely threatens global oilseed rape (Brassica napus L.) production. This study demonstrates that CRISPR/Cas9-mediated knockout of two homologous BnaFAH, involved in tyrosine degradation, confers enhanced Brassica napus resistance to Plutella xylostella under a 2-day short-day (SD2) photoperiod. Multi-omics analyses revealed that this resistance is associated with a coordinated response: BnaFAH deficiency triggers reactive oxygen species (ROS) accumulation, which is closely associated with activating the jasmonic acid (JA) biosynthetic and signaling pathways. This led to significant upregulation of key JA biosynthetic genes and accumulation of JA, its precursors (OPDA, OPC-4, and OPC-6), and bioactive conjugates (JA-Ile and JA-Phe). Pharmacological analyses support the central role of JA, as exogenous application of methyl jasmonate (MeJA) enhanced insect resistance, whereas the JA biosynthesis inhibitor DIECA suppressed resistance. Scavenging ROS with sodium selenite prevented both JA pathway upregulation and insect resistance, suggesting that ROS may act upstream to activate the JA biosynthetic and signaling pathways. These findings support a previously unrecognized “photoperiod-dependent ROS-JA” defense module, revealing how metabolic perturbation under specific environmental cues can be co-opted to enhance plant immunity, offering new targets for breeding resistant rapeseed varieties. Full article

Narrowing the bandgap of wide-bandgap oxides and controlling defects are crucial ways of enhancing the properties of functional materials. One important way to develop multifunctional hybrids is to transform non-conjugated polymers into oxide nanocomposites. To expand the broad-spectrum applications of wide-bandgap oxides, ZnO-based nanocomposites were synthesised using cross-linking non-conjugated polymers via one-pot carbonisation. As polymer-derived nanocomposites exhibit significant scattering noise, the grain boundaries of the nanocomposites were filled using additives that have an electronic effect. Optimising the grain boundaries in this way significantly decreased the scattering noise, avoided large fluctuations in baseline current and enhanced the interfacial charge transfer in broadband light spectral regions. The electronic effects of the used additives can effectively passivate defects in the polymer-derived oxide nanocomposites’ aggregation state, improving photocurrent extraction. Even after storage at room temperature for two years, the optimised nanocomposite exhibited favourable photocurrent signals when excited using typical light sources at wavelengths of 650, 808, 980 and 1064 nm. This nanocomposite has potential applications in interdisciplinary fields involving light harvesting. This study provides a simple, environmentally friendly strategy to creating multifunctional hybrids using non-conjugated polymers as precursors. Full article

Donor–acceptor (D-A)-type conjugated porous polymers (CPPs) have emerged as highly competitive photocatalysts for aerobic oxidation reactions. Herein, we rationally design and synthesize a series of D-A structured photocatalysts by employing dibenzothiophene-S, S-dioxide (BTDO) as the acceptor unit, and 4,8-bis(thiophen-2-yl) benzo [1,2-b:4,5-b’] dithiophene (DBD) and pyrene (Py) as the donor units. The effects of acceptor content on the optoelectronic and photocatalytic properties are systematically investigated. With the gradual increase in BTDO proportion and the decrease in pyrene content, the photocatalysts exhibit gradually narrowed band gaps, significantly promoted charge separation efficiency, and broadened visible light absorption range. Among the five as-prepared photocatalysts, DBD-T displays superior catalytic performance toward blue light-driven aerobic oxidation. Under mild conditions, benzyl sulfide and benzyl amine are selectively converted into benzyl sulfoxide and benzyl imine with a high conversion efficiency up to 96%. Moreover, DBD-T shows good universality toward a wide range of substrates, together with excellent recyclability and long-term stability. This work demonstrates that enhancing the electron-withdrawing capability of the acceptor unit represents a feasible and effective strategy to boost the photocatalytic performance of D-A-type conjugated polymers. Full article