Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Development of a machine-learning model to identify the impacts of pesticides characteristics on soil microbial communities from high-throughput sequencing data.

High-throughput sequencing (HTS) of soil environmental DNA provides an advanced insight into the effects of pesticides on soil microbial systems. However, the association between the properties of the pesticide and its ecological impact remains methodically challenging. Risks associated with pesticide use can be minimized if pesticides with optimal structural traits were applied. For this purpose, we merged the 20 independent HTS studies, to reveal that pesticides significantly reduced beneficial bacteria associated with soil and plant immunity, enhanced the human pathogen and weaken the soil's ecological stability. Through the machine-learning approach, correlating these impacts with the physicochemical properties of the pesticides yielded a random forest model with good predictive capabilities. The models revealed that physical pesticide properties such as the dissociation constant (pKa), the molecular weight and water solubility, determined the ecological impact of pesticides to a large extent. Moreover, this study identified that eco-friendly pesticides should possess a value of pKa > 5 and a molecular weight in the range of 200-300 g/mol, which were found to be conducive to bacteria related to plant immunity promotion and exerted the lowest fluctuation of human opportunistic pathogen and keystone species. This guides the design of pesticides for which the impacts on soil biota are minimized.

Effect of artemisinin-piperaquine treatment on the electrocardiogram of malaria patients

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

Comparison of 18FDG PET/PET-CT and bone scintigraphy for detecting bone metastases in patients with nasopharyngeal cancer: a meta-analysis.

OBJECTIVE: We performed a meta-analysis to compare the diagnostic efficacy of 18FDG PET/PET-CT and bone scintigraphy (BS) for diagnosing bone metastatic cancers in nasopharyngeal cancer patients. RESULTS: 6 studies (1238 patients) fulfilled the inclusion criteria. The pooled sensitivities for 18FDG PET/PET-CT and BS were 0.81 (95% confidence interval [CI] = 0.70 to 0.98) and 0.39 (95% CI = 0.26 to 0.54), specificities were 0.99 (95% CI = 0.98 to 0.99) and 0.98 (95% CI = 0.96 to 0.99), and the areas under curve were 0.98 (95% CI = 0.97 to 0.99) and 0.84 (95% CI = 0.81 to 0.87). MATERIALS AND METHODS: Several databases were searched for all available articles. We calculated the sensitivities, specificities, diagnostic odds ratios, likelihood ratios, and area under summary receiver operating characteristic curves for 18FDG PET/PET-CT and BS, respectively. CONCLUSIONS: 18FDG PET/PET-CT is superior to BS for diagnosing bone metastases in nasopharyngeal cancer patients.18FDG PET/PET-CT may enhance the diagnosis of bone metastases and provide more accurate information for the optimal management of nasopharyngeal cancer.

Distinct physiological and molecular responses in Arabidopsis thaliana exposed to aluminum oxide nanoparticles and ionic aluminum.

Nano-aluminium oxide (nAl2O3) is one of the most widely used nanomaterials. However, nAl2O3 toxicity mechanisms and potential beneficial effects on terrestrial plant physiology remain poorly understood. Such knowledge is essential for the development of robust nAl2O3 risk assessment. In this study, we studied the influence of a 10-d exposure to a total selected concentration of 98 µM nAl2O3 or to the equivalent molar concentration of ionic Al (AlCl3) (196 µM) on the model plant Arabidopsis thaliana on the physiology (e.g., growth and photosynthesis, membrane damage) and the transcriptome using a high throughput state-of-the-art technology, RNA-seq. We found no evidence of nAl2O3 toxicity on photosynthesis, growth and lipid peroxidation. Rather the nAl2O3 treatment stimulated root weight and length by 48% and 39%, respectively as well as photosynthesis opening up the door to the use of nAl2O3 in biotechnology and nano agriculture. Transcriptomic analyses indicate that the beneficial effect of nAl2O3 was related to an increase in the transcription of several genes involved in root growth as well as in root nutrient uptake (e.g., up-regulation of the root hair-specific gene family and root development genes, POLARIS protein). By contrast, the ionic Al treatment decreased shoot and root weight of Arabidopsis thaliana by 57.01% and 45.15%, respectively. This toxic effect was coupled to a range of response at the gene transcription level including increase transcription of antioxidant-related genes and transcription of genes involved in plant defense response to pathogens. This work provides an integrated understanding at the molecular and physiological level of the effects of nAl2O3 and ionic Al in Arabidopsis.

Influences of an Aluminum Covering Layer on the Performance of Cross-Like Hall Devices.

This work studies the effects of an aluminum covering on the performance of cross-like Hall devices. Four different Hall sensor structures of various sizes were designed and fabricated. The sensitivity and offset of the Hall sensors, two key points impacting their performance, were characterized using a self-built measurement system. The work analyzes the influences of the aluminum covering on those two aspects of the performance. The aluminum layer covering mainly leads to an eddy-current effect in an unstable magnetic field and an additional depletion region above the active region. Those two points have influences on the sensitivity and the offset voltage, respectively. The analysis guides the designer whether to choose covering with an aluminum layer the active region of the Hall sensor as a method to reduce the flicker noise and to improve the stability of the Hall sensor. Because Hall devices, as a reference element, always suffer from a large dispersion, improving their stability is a crucial issue.