Imaging the Iodine Sorption-Induced Synchronous Skeleton-Pore Interactions of Single Covalent Organic Framework Particles.

Covalent organic frameworks (COFs) are promising iodine adsorbents. For improved performances, it is critical and essential to fundamentally understand the underlying mechanism. Here, using the operando dark-field optical microscopy (DFM) imaging technique, the observation of an extraordinary structure shrinkage of 2D triphenylbenzene (TPB)-dimethoxyterephthaldehyde (DMTP)-COF upon the adsorption of I2 vapor at the single-particle resolution is reported. Combining single-particle DFM imaging with other experimental and theoretical methods, it is revealed that the shrinkage mechanism of the TPB-DMTP-COF is attributed to the I2 sorption-induced synchronous skeleton-pore interactions. The redox reaction of I2 and TPB-DMTP-COF yields some cationic skeletons and I3 - species, which triggers the multi-directional halogen-bonding interactions of I2 and I3 - as well as strong cation-π interactions between neutral and cationic skeletons, accompanying the synchronous in-plane skeleton shrinking in the xy plane and compact out-of-plane layer packing in the z-direction. This understanding of the synchronous action between the skeleton and pore breaks the perspective on the structure robustness of 2D COFs with excellent stability during the I2 uptake, which offers pivotal guidance for the rational design and creation of advanced microporous adsorbents.

Real-Time Imaging of Interfacial Copper(II) Ion-Initiated Selective Etching in the Core Region of Single Cuprous Oxide-Bismoclite Core-Shell Microcrystals.

The core-shell microstructures are attracting much interest, most notably for their superior performance compared with their pure counterparts because of the interfacial effect. Comprehensively understanding the mechanism of the interfacial effect is critical but still elusive. Here, we report real-time dark-field optical microscopy (DFM) imaging of the selective etching in the core region of single cuprous oxide-bismoclite (Cu2O@BiOCl) core-shell microcrystals by I-. In situ DFM observations reveal that the reaction activity of Cu2O is significantly improved after coating the BiOCl shell layer, and the I- diffuses through the BiOCl shell and approaches the interface region, followed by etching the Cu2O core. During the etching process, two distinct reaction pathways, such as interfacial Cu2+-driven redox etching and confinement-governed dissolution, are identified. The interfacial Cu2+ is generated due to the coordination number difference at the core-shell interface. Moreover, according to the in situ DFM single-crystal imaging results, the ensemble adsorption capacity improvement for I- is also demonstrated in Cu2O@BiOCl core-shell microcrystals. These findings provide deep insights into the interfacial effect of core-shell microcrystals and establish a bridge between microscopic imaging and macroscopic practical application.

Exploring the safety profile of tremelimumab: an analysis of the FDA adverse event reporting system.

BACKGROUND: Despite the approval of tremelimumab in 2022, there is a lack of pharmacovigilance studies investigating its safety profile in real-world settings using the FDA Adverse Event Reporting System (FAERS) database. AIM: This pharmacovigilance study aimed to comprehensively explore the adverse events (AEs) associated with tremelimumab using data mining techniques on the FAERS database. METHOD: The study utilized data from the FAERS database, covering the period from the first quarter of 2004 to the third quarter of 2022. Disproportionality analysis, the Benjamini Hochberg adjustment method and volcano plots were used to identify and evaluate AE signals associated with tremelimumab. RESULTS: The study uncovered 233 AE cases associated with tremelimumab. Among these cases, pyrexia (n = 39), biliary tract infection (n = 23), and sepsis (n = 21) were the three main AEs associated with tremelimumab use. The study also investigated the system organ classes associated with tremelimumab-related AEs. The top three classes were gastrointestinal disorders (17.9%), infections and infestations (16.6%), and general disorders and administration site infections (11.2%). Several AEs were identified that were not listed on the drug label of tremelimumab. These AEs included pyrexia, biliary tract infection, sepsis, dyspnea, infusion site infection, hiccup, appendicitis, hypotension, dehydration, localised oedema, presyncope, superficial thrombophlebitis and thrombotic microangiopathy. CONCLUSION: This pharmacovigilance study identified several potential adverse events signals related to tremelimumab including some adverse events not listed on the drug label. However, further basic and clinical research studies are needed to validate these results.

A novel mechanism of Vildagliptin in regulating bone metabolism and mitigating osteoporosis.

Osteoporosis has become a global social problem with the tendency toward the aging population. The challenge in managing osteoporosis is to develop new anti-osteoporosis drugs that target bone anabolism. The purpose of this study was to uncover the novel mechanism of Vildagliptin on bone metabolism. We revealed that Vildagliptin significantly promoted osteogenic differentiation of precursor osteoblasts and bone marrow mesenchymal stem cells (BMSCs). At the same time, it significantly enhanced the polarization of RAW264.7 macrophages to the M2 type and the secretion of osteogenic factors BMP2 and TGF-ß1. This was confirmed by the increased osteogenic differentiation observed in the osteoblast-RAW264.7 co-culture system. Moreover, Vildagliptin significantly enhanced the transformation of BMSCs into the osteogenic morphology in the osteoblast-BMSC co-culture system. Finally, Vildagliptin also inhibited osteoclastic differentiation of RAW 264.7 cells. The potential mechanism underlying these effects involved targeting the GAS6/AXL/ERK5 pathway. In the in vivo study, Vildagliptin significantly alleviated postmenopausal osteoporosis in ovariectomized mice. These findings represent the first comprehensive revelation of the regulatory effect of Vildagliptin on bone metabolism. Specifically, Vildagliptin demonstrates the ability to promote bone anabolism and inhibit bone resorption by simultaneously targeting osteoblasts, BMSCs, and osteoclasts. The bone-protective effects of Vildagliptin were further confirmed in a postmenopausal osteoporosis model. The clinical significance of this study lies in laying a theoretical foundation for bone protection therapy in type-2 diabetes patients with compromised bone conditions or postmenopausal osteoporosis.