Efficient Protein Synthesis In article 2200023, Qi and co-workers show that by orthogonal degradation of the targeted protein, both essential and alternative termination types of machinery are completely removed from E. coli cell extract. Furthermore, a total of 153 engineered tRNAs are screened for efficient all stop-codons decoding to construct a codon-dependent termination defect in vitro protein synthesis with all 64 sense-codons, iPSSC, which holds potential in building artificial protein synthesis beyond the cell.
Cerebral ischemia–reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (H2O2). However, the accurate measurement of mitochondrial viscosity and H2O2 levels in CIRI is challenging because of the lack of sufficient selectivity and blood–brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and H2O2 in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (Mito-IQS), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and H2O2 in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and H2O2 levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and H2O2 levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.
Abstract Studying numerous biologically important species simultaneously is crucial to understanding cellular functions and the root causes of related diseases. Direct visualization of endogenous biothiols in biological systems is of great value to understanding their biological roles. Herein, a novel multi‐signal fluorescent probe was rationally designed and exploited for the simultaneous sensing of homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) using different emission channels. This probe was successfully applied to the simultaneous discrimination between and visualization of endogenous Hcy, Cys, GSH, and their transformation in living cells.
Abstract Studying numerous biologically important species simultaneously is crucial to understanding cellular functions and the root causes of related diseases. Direct visualization of endogenous biothiols in biological systems is of great value to understanding their biological roles. Herein, a novel multi‐signal fluorescent probe was rationally designed and exploited for the simultaneous sensing of homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) using different emission channels. This probe was successfully applied to the simultaneous discrimination between and visualization of endogenous Hcy, Cys, GSH, and their transformation in living cells.
Objective To study the effects of long-term use of glucocorticoid nasal drops on bone density in adults. Methods A 2-year randomized study was conducted on the effects of glucocorticoid nasal drops on bone density in 26 adult patients with allergic rhinitis. Results Serum calcium,phosphorus,alkaline phosphatase, and bone density were determined before and after the treatment. No significant defference was found between treatment group and normal control group (P0.05). Conclusions Long-term use of glucocorticoid nasal drops in adult patients does not lead to osteoporosis if the lowest effective steroid dose is given.
The monitoring of heavy transition metals has increasingly attracted great attention because they pollute the environment and have unique physiological functions. Chemosensors are useful tools for monitoring heavy transition metals due to their simple visualization, excellent sensitivity and high selectivity. Herein, we have developed a novel chemosensor for the detection of water-soluble Cu2+ and Ni2+ species with different mechanisms, and low detection limits of 2.1 nM for Cu2+ and 1.2 nM for Ni2+ were obtained. The colorimetric probe CPH has been applied to qualitative and quantitative detection of Cu2+ and Ni2+ species in real samples.
Drug discovery is vitally important for protecting human against disease. Target-based screening is one of the most popular methods to develop new drugs in the past several decades. This method efficiently screens candidate drugs inhibiting target protein in vitro, but it often fails due to inadequate activity of the selected drugs in vivo. Accurate computational methods are needed to bridge this gap. Here, we propose a novel graph multi task deep learning model to identify compounds carrying both target inhibitory and cell active (MATIC) properties. On a carefully curated SARS-CoV-2 dataset, the proposed MATIC model shows advantages comparing with traditional method in screening effective compounds in vivo. Next, we explored the model interpretability and found that the learned features for target inhibition (in vitro) or cell active (in vivo) tasks are different with molecular property correlations and atom functional attentions. Based on these findings, we utilized a monte carlo based reinforcement learning generative model to generate novel multi-property compounds with both in vitro and in vivo efficacy, thus bridging the gap between target-based and cell-based drug discovery.
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