A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal–organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.</p

Study of Fungal Decomposition Rate

Abstract Fungi are critical to the carbon cycle. The growth rate model of fungi was constructed from three aspects of temperature, humidity and pH, and the moisture tolerance model of fungi was constructed from two aspects of competitive ranking and water ecotone width. Combined with related references, a fungal decomposition rate model was constructed based on the growth rate and moisture tolerance models. Under the given environmental conditions, the decomposer mass change curve was obtained by solving with MATLAB software, and the effect of environmental changes on the curve trend was investigated by the control variable method. The curve of decomposer mass change was obtained by calculating the competitive rank of the population and combining it with the fungal decomposition rate model.</jats:p

Plasma levels and potential roles of catestatin in patients with coronary heart disease

Objectives. Catestatin (CST) is a new endogenous neuropeptide with a potent catecholamine release-inhibitory activity. This study was to investigate plasma CST levels in patients with coronary heart disease (CHD) and to determine the clinical significance of plasma CST in cardiovascular events. Methods. A total of 120 CHD patients and 30 age/sex-matched healthy subjects were enrolled. Plasma CST level was measured using enzyme-linked immunosorbent assay (ELISA) and norepinephrine (NE) level was measured using high-performance liquid chromatography (HPLC). Clinical and laboratory data during hospitalization were collected, and a follow-up of 1045 days was carried out. Results. Compared with controls, CHD patients had significantly higher plasma CST and NE levels on admission. ST segment elevation myocardial infarction (STEMI) patients had higher CST levels than angina pectoris patients had, but CST/NE ratios were unchanged among controls and different CHD subgroups. Plasma NE was the only independent factor associated with CST. As a dichotomous variable divided by the median value, plasma CST on admission was not associated with adverse cardiovascular events. Conclusions. Plasma CST level was positively correlated with that of NE and was elevated in parallel with that of NE in the different myocardial ischemia states. Plasma CST on admission was neither associated with adverse cardiac events nor was there any significant relationship between plasma CST and onset of new cardiovascular events. The pathophysiological role of CST in CHD needs further studies.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000322607700004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cardiac &amp; Cardiovascular SystemsSCI(E)PubMed4ARTICLE4217-2244