Development of Novel Membrane Disrupting Lipoguanidine Compounds Sensitizing Gram-Negative Bacteria to Antibiotics.

A new class of amphiphilic molecules, the lipoguanidines, designed as hybrids of guanidine and fatty acid compounds, has been synthesized and developed. The new molecules present both a guanidine polar head and a lipophilic tail that allow them to disrupt bacterial membranes and to sensitize Gram-negative bacteria to the action of the narrow-spectrum antibiotics rifampicin and novobiocin. The lipoguanidine 5g sensitizes Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to rifampicin, thereby reducing the antibiotic minimum inhibitory concentrations (MIC) up to 256-fold. Similarly, 5g is able to potentiate novobiocin up to 64-fold, thereby showing a broad spectrum of antibiotic potentiating activity. Toxicity and mechanism studies revealed the potential of 5g to work synergistically with rifampicin through the disruption of bacterial membranes without affecting eukaryotic cells.

Oxazolidinones as versatile scaffolds in medicinal chemistry.

Oxazolidinone is a five-member heterocyclic ring with several biological applications in medicinal chemistry. Among the three possible isomers, 2-oxazolidinone is the most investigated in drug discovery. Linezolid was pioneered as the first approved drug containing an oxazolidinone ring as the pharmacophore group. Numerous analogues have been developed since its arrival on the market in 2000. Some have succeeded in reaching the advanced stages of clinical studies. However, most oxazolidinone derivatives reported in recent decades have not reached the initial stages of drug development, despite their promising pharmacological applications in a variety of therapeutic areas, including antibacterial, antituberculosis, anticancer, anti-inflammatory, neurologic, and metabolic diseases, among other areas. Therefore, this review article aims to compile the efforts of medicinal chemists who have explored this scaffold over the past decades and highlight the potential of the class for medicinal chemistry.

Intelligent speech technologies for transcription, disease diagnosis, and medical equipment interactive control in smart hospitals: A review.

The growing and aging of the world population have driven the shortage of medical resources in recent years, especially during the COVID-19 pandemic. Fortunately, the rapid development of robotics and artificial intelligence technologies help to adapt to the challenges in the healthcare field. Among them, intelligent speech technology (IST) has served doctors and patients to improve the efficiency of medical behavior and alleviate the medical burden. However, problems like noise interference in complex medical scenarios and pronunciation differences between patients and healthy people hamper the broad application of IST in hospitals. In recent years, technologies such as machine learning have developed rapidly in intelligent speech recognition, which is expected to solve these problems. This paper first introduces IST's procedure and system architecture and analyzes its application in medical scenarios. Secondly, we review existing IST applications in smart hospitals in detail, including electronic medical documentation, disease diagnosis and evaluation, and human-medical equipment interaction. In addition, we elaborate on an application case of IST in the early recognition, diagnosis, rehabilitation training, evaluation, and daily care of stroke patients. Finally, we discuss IST's limitations, challenges, and future directions in the medical field. Furthermore, we propose a novel medical voice analysis system architecture that employs active hardware, active software, and human-computer interaction to realize intelligent and evolvable speech recognition. This comprehensive review and the proposed architecture offer directions for future studies on IST and its applications in smart hospitals.

Multi-omics approaches to studying gastrointestinal microbiome in the context of precision medicine and machine learning.

The human gastrointestinal (gut) microbiome plays a critical role in maintaining host health and has been increasingly recognized as an important factor in precision medicine. High-throughput sequencing technologies have revolutionized -omics data generation, facilitating the characterization of the human gut microbiome with exceptional resolution. The analysis of various -omics data, including metatranscriptomics, metagenomics, glycomics, and metabolomics, holds potential for personalized therapies by revealing information about functional genes, microbial composition, glycans, and metabolites. This multi-omics approach has not only provided insights into the role of the gut microbiome in various diseases but has also facilitated the identification of microbial biomarkers for diagnosis, prognosis, and treatment. Machine learning algorithms have emerged as powerful tools for extracting meaningful insights from complex datasets, and more recently have been applied to metagenomics data via efficiently identifying microbial signatures, predicting disease states, and determining potential therapeutic targets. Despite these rapid advancements, several challenges remain, such as key knowledge gaps, algorithm selection, and bioinformatics software parametrization. In this mini-review, our primary focus is metagenomics, while recognizing that other -omics can enhance our understanding of the functional diversity of organisms and how they interact with the host. We aim to explore the current intersection of multi-omics, precision medicine, and machine learning in advancing our understanding of the gut microbiome. A multidisciplinary approach holds promise for improving patient outcomes in the era of precision medicine, as we unravel the intricate interactions between the microbiome and human health.

Antibacterial triterpenoids from the leaves of Ilex hainanensis Merr.

One new triterpenoid (1) and seven known analogues (2-8) were isolated from the leaves of Ilex hainanensis Merr.. Their structures were established by analysis of their MS, 1D and 2D NMR spectroscopic data and comparison with those in the literature. The antibacterial activity of compounds 1-8 were evaluated by determination of minimum inhibitory concentration using twofold microdilution broth method against Streptococcus mutans ATCC 25175 (Gram-positive) and Fusobacterium nucleatum ATCC 10953 (Gram-negative). Compounds 3 and 5 showed significant antibacterial activity against S. mutans in concentration of 9.7 µg/mL, while showed little antibacterial activity against F. nucleatum. On the contrary, the inhibitory activity of compounds 1, 2 and 6 against F. nucleatum were higher than them against S. mutans.

[Determination of three pair of triterpenoid isomers in leaf of Ilex hainanensis by HPLC-ELSD].

The present study is to develop an HPLC-ELSD method for simultaneous determination of three pairs of triterpenoid isomers, Ilexsaponin A1, Ilexhainanoside D, Ilexgenin A, 3ß, 19α-dihydroxyolean-12-ene-24, 28-dioic acid (ilexhainanin E) ursolic acid and oleanic acid in the leaf of Ilex hainanensis, which could provide evidence to the quality control of this herb. The six constituents were measured on a Waters XBridge C18 column (4.6 mm×250 mm, 5 µm), with a mobile phase consisting of methanol (A)- 0.5% formic acid in water (B) at a flow rate of 1.0 mL·min⁻¹ (0-18 min，70%-85% A，18-20 min，85%-95% A；20-35 min，95% A). The carrier gas was N2, and the pressure was 2.8 L·min⁻¹. The drift tube in this experiment were set at 70 °C. The injection volume was 10 µL. The contents of the six triterpenoids in 6 samples were 3.7-8.5, 10.3 -22.1, 2.8-5.9, 7.8-14.1, 2.6-3.8 and 8.8-11.9 mg·g⁻¹, respectively. The established method is proved to be accurate and sensitive for the determination of triterpenoids in Ilicis Hainanensis Folium, and may be used for the quality improvement of this herb.

Impact of extended ginsenoside Rb1 on early chronic kidney disease: a randomized, placebo-controlled study.

Ginsenoside Rb1 (GS-Rb1) is a well-known antioxidant derived from traditionally used herbal medicine ginseng. It has been suggested that reactive oxygen species (ROS) is involved in chronic kidney disease (CKD) in which GS-Rb1 may play a protective role. The aim of this study was to evaluate prospectively the effects of GS-Rb1 in patients with early chronic kidney disease. 197 patients who have been diagnosed with early CKD (stage 2 or 3) were recruited and randomly assigned to receive GS-Rb1 (500 mg daily oral administration, n = 103) or placebo (n = 94) for consecutive 6 months. Analytical procedures performed at baseline, the end of the treatments, and 6 months after the treatments included renal function evaluation (creatinine and urea clearance), oxidative stress measurement, inflammation assessment, and lipid profile. Of 177 patients completing the study, the GS-Rb1 group (n = 91) showed a positive response in significantly alleviating renal function impairments compared to the placebo group (n = 86). In addition, GS-Rb1 treatment was effective in reducing the extent of oxidative stress and inflammation in CKD patients, whereas continued deterioration was observed in the placebo group. Thus, extended treatment of patients using GS-Rb1 may present an antioxidant-based approach to slow the progression of CKD at the early stages.