The proper class generated by weak supplements

We show that, for hereditary rings, the smallest proper classes containing respectively the classes of short exact sequences determined by small submodules, submodules that have supplements and weak supplement submodules coincide. Moreover, we show that this class can be obtained as a natural extension of the class determined by small submodules. We also study injective, projective, coinjective and coprojective objects of this class. We prove that it is coinjectively generated and its global dimension is at most 1. Finally, we describe this class for Dedekind domains in terms of supplement submodules.TUBITAK (107T709

Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy

<div><p>Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-<i>g</i>-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. <i>In vivo</i> pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.</p></div

<i>In vitro</i> anti-tumor activity of DEX-IND/PTX micelles.

<p>(A, B) Cytotoxicity of DEX-IND micelles without PTX encapsulation in MCF-7 and MCF-7/ADR cells for 24 h (n = 3). (C, D) The viability of MCF-7/ADR cells after incubation with PTX, PTX + IND and DEX-IND/PTX micelles for 24 h. Data represent mean ± standard deviation (n = 3). *<i>P</i> < 0.05.</p

Preparation and characterization of DEX-IND micelles.

<p>(A) Synthetic route of DEX-IND polymer. (B) ^<i>1</i><i>H</i> NMR spectra. (C) Negative-stain transmission electron microscopy of DEX-IND and DEX-IND/PTX micelles. (D) Characteristics of DEX-IND and DEX-IND/PTX micelles.</p

Plasma pharmacokinetic parameters of PTX after intravenous administration of Taxol and DEX-IND/PTX micelles in rats (n = 5).

<p>Plasma pharmacokinetic parameters of PTX after intravenous administration of Taxol and DEX-IND/PTX micelles in rats (n = 5).</p

<i>In vitro</i> anti-tumor activity of DEX-IND/PTX micelles.

<p>(A, B) Cytotoxicity of DEX-IND micelles without PTX encapsulation in MCF-7 and MCF-7/ADR cells for 24 h (n = 3). (C, D) The viability of MCF-7/ADR cells after incubation with PTX, PTX + IND and DEX-IND/PTX micelles for 24 h. Data represent mean ± standard deviation (n = 3). *<i>P</i> < 0.05.</p

Stability and <i>in vitro</i> release of DEX-IND/PTX micelles.

<p>(A, B) <i>In vitro</i> stability of DEX-IND/PTX micelles at 4°C, including size and PDI. (C) <i>In vitro</i> release profiles of free PTX and DEX-IND/PTX micelles in pH 7.4 PBS, and DEX-IND/PTX micelles in pH 5.0 PBS. Data represent mean ± standard deviation (n = 3).</p

The concentration versus time curve of PTX and DEX-IND/PTX after intravenous administration.

<p>Data represent mean ± standard deviation (n = 5).</p

<i>In vivo</i> antitumor activities of PTX and DEX-IND/PTX after intravenous administration tumor-bearing mice.

<p>(A) Mice tumor volume changes within 48 days. (B) Mice body weight changes within 48 days. Data represent mean ± standard deviation (n = 5).</p

Self-Powered, One-Stop, and Multifunctional Implantable Triboelectric Active Sensor for Real-Time Biomedical Monitoring

Operation time of implantable electronic devices is largely constrained by the lifetime of batteries, which have to be replaced periodically by surgical procedures once exhausted, causing physical and mental suffering to patients and increasing healthcare costs. Besides the efficient scavenging of the mechanical energy of internal organs, this study proposes a self-powered, flexible, and one-stop implantable triboelectric active sensor (iTEAS) that can provide continuous monitoring of multiple physiological and pathological signs. As demonstrated in human-scale animals, the device can monitor heart rates, reaching an accuracy of ∼99%. Cardiac arrhythmias such as atrial fibrillation and ventricular premature contraction can be detected in real-time. Furthermore, a novel method of monitoring respiratory rates and phases is established by analyzing variations of the output peaks of the iTEAS. Blood pressure can be independently estimated and the velocity of blood flow calculated with the aid of a separate arterial pressure catheter. With the core–shell packaging strategy, monitoring functionality remains excellent during 72 h after closure of the chest. The in vivo biocompatibility of the device is examined after 2 weeks of implantation, proving suitability for practical use. As a multifunctional biomedical monitor that is exempt from needing an external power supply, the proposed iTEAS holds great potential in the future of the healthcare industry