Second-Generation AUTACs for Targeted Autophagic Degradation.

Targeted protein degradation via the ubiquitin-proteasome system has emerged as one of the most promising drug discovery modalities. Autophagy, another intracellular degradation system, can target a wide range of nonproteinous substrates as well as proteins, but its application to targeted degradation is still in its infancy. Our previous work revealed a relationship between guanine modification of cysteine residues on intracellular proteins and selective autophagy, resulting in the first autophagy-based degraders, autophagy-targeted chimeras (AUTACs). Based on the research background, all the reported AUTACs compounds contain cysteine as a substructure. Here, we examine the importance of this substructure by conducting SAR studies and report significant improvements in the degrader's activity by replacing cysteine with other moieties. Several derivatives showed sub-µM range degrading activity, demonstrating the increased practical value of AUTACs.

Effectiveness of Infection Control Teams in Reducing Healthcare-Associated Infections: A Systematic Review and Meta-Analysis.

The infection control team (ICT) ensures the implementation of infection control guidelines in healthcare facilities. This systematic review aims to evaluate the effectiveness of ICT, with or without an infection control link nurse (ICLN) system, in reducing healthcare-associated infections (HCAIs). We searched four databases to identify randomised controlled trials (RCTs) in inpatient, outpatient and long-term care facilities. We judged the quality of the studies, conducted meta-analyses whenever interventions and outcome measures were comparable in at least two studies, and assessed the certainty of evidence. Nine RCTs were included; all were rated as being low quality. Overall, ICT, with or without an ICLN system, did not reduce the incidence rate of HCAIs [risk ratio (RR) = 0.65, 95% confidence interval (CI): 0.45-1.07], death due to HCAIs (RR = 0.32, 95% CI: 0.04-2.69) and length of hospital stay (42 days vs. 45 days, p = 0.52). However, ICT with an ICLN system improved nurses' compliance with infection control practices (RR = 1.17, 95% CI: 1.00-1.38). Due to the high level of bias, inconsistency and imprecision, these findings should be considered with caution. High-quality studies using similar outcome measures are needed to demonstrate the effectiveness and cost-effectiveness of ICT.

Enhancing hospital quality management and patient safety in Vietnam: a technical assistance project utilizing online solutions during COVID-19 pandemic.

Since 2015, the National Center for Global Health and Medicine in Japan has been conducting a technical assistance project for improving patient safety in Vietnamese hospitals. During the COVID-19 pandemic, the project conducted a patient safety training program utilizing online solutions for participants from Vietnam. This resulted in an increase in the number of participants, and ensured access from remote locations. The convenience of easy access from smartphones encouraged further participation. In addition to online training, the utilization of platforms such as Facebook, a common social networking service in Vietnam, contributed to the dissemination of good practices.

AUTACs: Cargo-Specific Degraders Using Selective Autophagy.

Protein silencing represents an essential tool in biomedical research. Targeted protein degradation (TPD) strategies exemplified by PROTACs are rapidly emerging as modalities in drug discovery. However, the scope of current TPD techniques is limited because many intracellular materials are not substrates of proteasomal clearance. Here, we described a novel targeted-clearance strategy (autophagy-targeting chimera [AUTAC]) that contains a degradation tag (guanine derivatives) and a warhead to provide target specificity. As expected from the substrate scope of autophagy, AUTAC degraded fragmented mitochondria as well as proteins. Mitochondria-targeted AUTAC accelerated both the removal of dysfunctional fragmented mitochondria and the biogenesis of functionally normal mitochondria in patient-derived fibroblast cells. Cytoprotective effects against acute mitochondrial injuries were also seen. Canonical autophagy is viewed as a nonselective bulk decomposition system, and none of the available autophagy-inducing agents exhibit useful cargo selectivity. With its target specificity, AUTAC provides a new modality for research on autophagy-based drugs.

Analysis of cationic amino acid transport activity in canine lens epithelial cells.

Cationic amino acid transport activity in a canine lens epithelial cells (LEC) line was investigated. The transporter activity of arginine was 0.424 ± 0.047 nmol/mg protein min, while the presence of N-ethylmaleimide, an inhibitor of the canine cationic amino acid transporter (CAT), reduced transport activity by 30%. A full-length cDNA sequence of canine CAT1 was 2558 bp long and was predicted to encode the 629 amino acid polypeptides. The deduced amino acid sequence of canine CAT1 showed similarities of 92.1% and 88.6% to those of the human and mouse, respectively. Western blot analysis detected a band at 70 kDa in a membrane protein sample of LEC. RT-PCR analysis confirmed that CAT1 was ubiquitously detected in all tissues examined.