Design,synthesis and biological evaluation of 2,5-dimethylfuran-3-carboxylic acid derivatives as potential IDO1 inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in tumor immune escape and has emerged as a promising target for cancer immunotherapy. In this study, a novel series of 2,5-dimethylfuran-3-carboxylic acid derivatives were designed, synthesized and evaluated for inhibitory activities against IDO1, and their structure-activity relationship was investigated. Among these, compound 19a exhibited excellent IDO1 inhibitory activity (HeLa cellular IC₅₀?=?4.0?nM, THP-1 cellular IC₅₀?=?4.6?nM). Further molecular docking studies revealed that the compound 19a formed a coordinate bond with the heme iron through the carboxylic acid moiety. These results indicate that compound 19a is a potential IDO1 inhibitor for further investigation.     

Study of cross talk between phosphatases and OGA on a ZO-3-derived peptide

Amino Acids - O-GlcNAcylation, like phosphorylation, is a dynamic and rapid posttranslational modification which regulates many cellular processes. Phosphorylation on tyrosine and O-GlcNAcylation...     

Is the removal of aboveground shrub biomass an effective technique to restore a shrub‐encroached grassland?

Encroachment of woody plants into grasslands is a global phenomenon that has substantial impacts on pastoral productivity and ecosystem services. Over the past half century, pastoralists and land management agencies have explored various options to control woody plants in order to improve ecosystem services in shrub‐encroached grasslands. We examined the effectiveness of controlling the encroachment of the shrub Caragana microphylla into grassland in Inner Mongolia, China. We cut and removed all of the aboveground biomass from 450 shrubs, predicting that the effectiveness of this technique to control shrubs would depend on shrub morphology. Specifically, we expected that larger shrubs with more biomass would be more difficult to kill by cutting than smaller shrubs. A year after treatment, we found that cutting killed only 11% of the 450 treated shrubs, and of these, three‐quarters of the locations that they occupied reverted to grasses and one‐quarter to bare soil. Shrubs that survived the cutting treatment produced more stems and leaf biomass, and therefore had a greater leaf to stem ratio. Shrubs that died after cutting had a lower crown area and basal area, and less stem biomass than shrubs that resprouted within 12 months of cutting. There were no effects of shrub height on the fate of treated shrubs. Cutting had no effect on understory plant cover or richness, but reproductive plants were taller under shrubs that were not cut. Overall, our study showed that removing aboveground shrub biomass by cutting is an ineffective technique for “restoring” the original grassland community unless shrubs are very small. Strategic targeting of small shrubs would be a more effective technique for controlling the spread of C. microphylla in the long term.     

Oncogenic Notch Promotes Long-Range Regulatory Interactions within Hyperconnected 3D Cliques

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Correction to: High-yield production of l-serine from glycerol by engineered Escherichia coli

Journal of Industrial Microbiology & Biotechnology - Unfortunately, the order of the figures 1-4 has been positioned wrongly in the print published article     

Molecular characteristics of microbially mediated transformations of Synechococcus-derived dissolved organic matter as revealed by incubation experiments

In this study, we investigated the microbially mediated transformation of labile Synechococcus-derived DOM to RDOM using a 60-day experimental incubation system. Three phases of TOC degradation activity (I, II and III) were observed following the addition of Synechococcus-derived DOM. The phases were characterized by organic carbon consumption rates of 8.77, 1.26 and 0.16 μmol L⁻¹ day⁻¹, respectively. Excitation emission matrix analysis revealed the presence of three FDOM components including tyrosine-like, fulvic acid-like, and humic-like molecules. The three components also exhibited differing biological availabilities that could be considered as labile DOM (LDOM), semi-labile DOM (SLDOM) and RDOM, respectively. DOM molecular composition was also evaluated using FT-ICR MS. Based on differing biological turnover rates and normalized intensity values, a total of 1704 formulas were identified as candidate LDOM, SLDOM and RDOM molecules. Microbial transformation of LDOM to RDOM tended to proceed from high to low molecular weight, as well as from molecules with high to low double bond equivalent (DBE) values. Relatively higher aromaticity was observed in the formulas of RDOM molecules relative to those of LDOM molecules. FDOM components provide valuable proxy information to investigate variation in the bioavailability of DOM. These results suggest that coordinating fluorescence spectroscopy and FT-ICR MS of DOM, as conducted here, is an effective strategy to identify and characterize LDOM, SLDOM and RDOM molecules in incubation experiments emulating natural systems. The results described here provide greater insight into the metabolism of phytoplankton photosynthate by heterotrophic bacteria in marine environments.     

Variations in carbon source–sink relationships in subalpine fir across elevational gradients

• Cold‐adapted trees display acclimation in both carbon source and carbon sink capacity to low‐temperature stress at their upper elevational range limits. Hence a balanced carbon source–sink capacity might be required for their persistence and survival at the elevational tree limits.
• The present study examined the spatial dynamics of carbon source–sink relationship in subalpine fir (Abies fargesii) trees along elevational gradients in the northern slope of the temperate region and in the southern slope of the subtropics in terms of climate in the Qinling Mountain range, north‐central China.
• The results showed that non‐structural carbohydrate (NSC) concentrations in both the source and sink tissues increased with the increase in elevation. The ratio of carbon source–sink displayed a consistent decreasing trend with the increase in elevation and during growing season, showing that it was lowest at a ratio of 2.93 in the northern slope and at a ratio of 2.61 in the southern slope at the upper distribution elevations in the late growing season. Such variations of carbon source–sink ratio might be attributable to the balance between carbon source and sink activities, which changed seasonally across the elevational distribution range.
• We concluded that a ratio of carbon source–sink of at least 2.6 might be essential for subalpine fir trees to persist at their upper range limits. Therefore, a sufficient source–sink ratio and a balanced source–sink relationship might be required for subalpine fir trees to survive and develop at their upper elevational distribution limits.