Furans

AlphaFold2 (AF2) is an artificial intelligence (AI) system developed by DeepMind that can predict three-dimensional (3D) structures of proteins from amino acid sequences with atomic-level accuracy. Protein structure prediction is one of the most challenging problems in computational biology and chemistry, and has puzzled scientists for 50 years. The advent of AF2 presents an unprecedented progress in protein structure prediction and has attracted much attention. Subsequent release of structures of more than 200 million proteins predicted by AF2 further aroused great enthusiasm in the science community, especially in the fields of biology and medicine. AF2 is thought to have a significant impact on structural biology and research areas that need protein structure information, such as drug discovery, protein design, prediction of protein function, et al. Though the time is not long since AF2 was developed, there are already quite a few application studies of AF2 in the fields of biology and medicine, with many of them having preliminarily proved the potential of AF2. To better understand AF2 and promote its applications, we will in this article summarize the principle and system architecture of AF2 as well as the recipe of its success, and particularly focus on reviewing its applications in the fields of biology and medicine. Limitations of current AF2 prediction will also be discussed.

The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005-2010, n = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0-13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.

BackgroundMicroglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary injury factor, which drives trauma-induced neurodegeneration and is lack of efficient treatment. ACT001, a sesquiterpene lactone derivative, is reportedly involved in alleviation of inflammatory response. However, little is known regarding its function in regulating innate immune response of central nervous system (CNS) after TBI. This study aimed to investigate the role and underlying mechanism of ACT001 in TBI.MethodsControlled cortical impact (CCI) models were used to establish model of TBI. Cresyl violet staining, evans blue extravasation, neurobehavioral function assessments, immunofluorescence and transmission electron microscopy were used to evaluate therapeutic effects of ACT001 in vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction models were established as co-culture system to simulate TBI conditions in vitro. Cytotoxic effect of ACT001 on cell viability was assessed by cell counting kit-8 and activation of microglia cells were induced by Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression was determined by Real-time PCR and nitric oxide production. Apoptotic cells were detected by TUNEL and flow cytometry assays. Tube formation was performed to evaluate cellular angiogenic ability. ELISA and western blot experiments were used to determine proteins expression. Pull-down assay was used to analyze proteins that bound ACT001.ResultsACT001 relieved the extent of blood-brain barrier integrity damage and alleviated motor function deficits after TBI via reducing trauma-induced activation of microglia cells. Delayed depletion of microglia with PLX5622 hindered therapeutic effect of ACT001. Furthermore, ACT001 alleviated LPS-induced activation in mouse and rat primary microglia cells. Besides, ACT001 was effective in suppressing LPS-induced pro-inflammatory cytokines production in BV2 cells, resulting in reduction of neuronal apoptosis in HT22 cells and improvement of tube formation in bEnd.3 cells. Mechanism by which ACT001 functioned was related to AKT/NFκB/NLRP3 pathway. ACT001 restrained NFκB nuclear translocation in microglia cells through inhibiting AKT phosphorylation, resulting in decrease of NLRP3 inflammasome activation, and finally down-regulated microglial neuroinflammatory response.ConclusionsOur study indicated that ACT001 played critical role in microglia-mediated neuroinflammatory response and might be a novel potential chemotherapeutic drug for TBI. Video Abstract.

ObjectiveTo assess the effectiveness of once- and twice-daily ritonavir-boosted darunavir (DRV/r)-containing regimens for treating HIV in pregnancy to inform the 2025 World Health Organization antiretroviral treatment guidelines update.DesignAnalysis of pooled data from two observational study networks with sites in Romania, Switzerland, and the United Kingdom.MethodsPregnancies resulting in a live birth or stillbirth in women receiving 800/100 mg DRV/r once-daily or 600/100 mg twice-daily during pregnancy were included. The primary outcome was viral suppression (ResultsAmong 162 women on once-daily DRV/r, 95% were virally suppressed near delivery, with no difference between those on DRV/r from conception (95%, 113/119) and those who started on or switched to DRV/r during pregnancy (95%, 41/43). Among 27 women on twice-daily DRV/r, 78% were virally suppressed near delivery. Most women remained on the same DRV/r regimen until delivery, and there were no vertical transmissions. Darunavir drug concentrations for the limited number of pregnancies with data available fell within the expected ranges.ConclusionsThis analysis provides some reassurance that once-daily DRV/r can be used successfully in pregnancy. However, given the possibility of reduced drug levels in pregnancy with once-daily dosing, viral load monitoring during pregnancy remains essential. Surveillance of pregnancies in women receiving once-daily DRV/r is needed to further support the use of this dosing during pregnancy.