While drinking water disinfection has effectively prevented waterborne diseases, an unintended consequence is the generation of disinfection byproducts (DBPs). Epidemiological studies have ...consistently observed an association between consumption of chlorinated drinking water with an increased risk of bladder cancer. Out of the >600 DBPs identified, regulations focus on a few classes, such as trihalomethanes (THMs), whose concentrations were hypothesized to correlate with the DBPs driving the toxicity of disinfected waters. However, the DBPs responsible for the bladder cancer association remain unclear. Utilities are switching away from a reliance on chlorination of pristine drinking water supplies to the application of new disinfectant combinations to waters impaired by wastewater effluents and algal blooms. In light of these changes in disinfection practice, this article discusses new approaches being taken by analytical chemists, engineers, toxicologists and epidemiologists to characterize the DBP classes driving disinfected water toxicity, and suggests that DBP exposure should be measured using other DBP classes in addition to THMs.
Solar-induced chlorophyll fluorescence (SIF) brings major advancements in measuring terrestrial photosynthesis. Several recent studies have evaluated the potential of SIF retrievals from the Orbiting ...Carbon Observatory-2 (OCO-2) in estimating gross primary productivity (GPP) based on GPP data from eddy covariance (EC) flux towers. However, the spatially and temporally sparse nature of OCO-2 data makes it challenging to use these data for many applications from the ecosystem to the global scale. Here, we developed a new global ‘OCO-2’ SIF data set (GOSIF) with high spatial and temporal resolutions (i.e., 0.05°, 8-day) over the period 2000–2017 based on a data-driven approach. The predictive SIF model was developed based on discrete OCO-2 SIF soundings, remote sensing data from the Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological reanalysis data. Our model performed well in estimating SIF (R2 = 0.79, root mean squared error (RMSE) = 0.07 W m−2 μm−1 sr−1). The model was then used to estimate SIF for each 0.05° × 0.05° grid cell and each 8-day interval for the study period. The resulting GOSIF product has reasonable seasonal cycles, and captures the similar seasonality as both the coarse-resolution OCO-2 SIF (1°), directly aggregated from the discrete OCO-2 soundings, and tower-based GPP. Our SIF estimates are highly correlated with GPP from 91 EC flux sites (R2 = 0.73, p < 0.001). They capture the expected spatial and temporal patterns and also have remarkable ability to highlight the crop areas with the highest daily productivity across the globe. Our product also allows us to examine the long-term trends in SIF globally. Compared with the coarse-resolution SIF that was directly aggregated from OCO-2 soundings, GOSIF has finer spatial resolution, globally continuous coverage, and a much longer record. Our GOSIF product is valuable for assessing terrestrial photosynthesis and ecosystem function, and benchmarking terrestrial biosphere and Earth system models.
Alzheimer's disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer's disease research; ...however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer's disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer's disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer's disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer's disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer's disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer's disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed.
Accurately quantifying gross primary production (GPP) globally is critical for assessing plant productivity, carbon balance, and carbon-climate feedbacks, while current GPP estimates exhibit ...substantial uncertainty. Solar-induced chlorophyll fluorescence (SIF) observed by the Orbiting Carbon Observatory-2 (OCO-2) has offered unprecedented opportunities for monitoring land photosynthesis, while its sparse coverage remains a bottleneck for mapping finer-resolution GPP globally. Here, we used the global, OCO-2-based SIF product (GOSIF) and linear relationships between SIF and GPP to map GPP globally at a 0.05° spatial resolution and 8-day time step for the period from 2000 to 2017. To account for the uncertainty of GPP estimates resulting from the SIF-GPP relationship, we used a total of eight SIF-GPP relationships with different forms (universal and biome-specific, with and without intercept) at both site and grid cell levels to estimate GPP. Our results showed that all of the eight SIF-GPP relationships performed well in estimating GPP globally. The ensemble mean 8-day GPP was generally highly correlated with flux tower GPP for 91 eddy covariance flux sites across the globe (R2 = 0.74, Root Mean Square Error = 1.92 g C m−2 d−1). Our fine-resolution GPP estimates showed reasonable spatial and seasonal variations across the globe and fully captured both seasonal cycles and spatial patterns present in our coarse-resolution (1°) GPP estimates based on coarse-resolution SIF data directly aggregated from discrete OCO-2 soundings. SIF-GPP relationships with different forms could lead to significant differences in annual GPP particularly in the tropics. Our ensemble global annual GPP estimate (135.5 ± 8.8 Pg C yr−1) is between the median estimate of non-process based methods and the median estimate of process-based models. Our GPP estimates showed interannual variability in many regions and exhibited increasing trends in many parts of the globe particularly in the Northern Hemisphere. With the availability of high-quality, gridded SIF observations from space (e.g., TROPOMI, FLEX), our novel approach does not rely on any other input data (e.g., climate data, soil properties) and therefore can map GPP solely based on satellite SIF observations and potentially lead to more accurate GPP estimates at regional to global scales. The use of a universal SIF-GPP relationship versus biome-specific relationships can also avoid the uncertainty associated with land cover maps. Our novel, independent GPP product (GOSIF GPP), freely available at our data repository, will be valuable for studying photosynthesis, carbon cycle, agricultural production, and ecosystem responses to climate change and disturbances, informing ecosystem management, and benchmarking terrestrial biosphere and Earth system models.
Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated. Here we ...report a DNAzyme motor that operates in living cells in response to a specific intracellular target. The whole motor system is constructed on a 20 nm gold nanoparticle (AuNP) decorated with hundreds of substrate strands serving as DNA tracks and dozens of DNAzyme molecules each silenced by a locking strand. Intracellular interaction of a target molecule with the motor system initiates the autonomous walking of the motor on the AuNP. An example DNAzyme motor responsive to a specific microRNA enables amplified detection of the specific microRNA in individual cancer cells. Activated by specific intracellular targets, these self-powered DNAzyme motors will have diverse applications in the control and modulation of biological functions.
Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next‐generation tetracycline that is the final line of defense against severe infections by ...pan‐drug‐resistant bacterial pathogens. Unfortunately, this last‐resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high‐level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next‐generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large‐scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram‐negative bacteria in both human and veterinary medicine.
The novel mobile tetracycline‐inactivating enzymes, Tet(X3)–Tet(X5), could confer high‐level tigecycline resistance. They have been disseminated in diverse bacterial hosts from a wide range of ecological niches through promiscuous plasmids and ISCR2. This complex dissemination can be driven by selective pressure from the massive use of the early tetracyclines.
Baicalin, which is isolated from Radix Scutellariae, possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of ...baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms.
A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression.
The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia.
Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.
Arabidopsis mutants produced by constitutive overexpression of the CRISPR/Cas9 genome editing system are usually mosaics in the T1 generation. In this study, we used egg cell-specific promoters to ...drive the expression of Cas9 and obtained non-mosaic T1 mutants for multiple target genes with high efficiency. Comparisons of 12 combinations of eight promoters and two terminators found that the efficiency of the egg cell-specific promoter-controlled CRISPR/Cas9 system depended on the presence of a suitable terminator, and the composite promoter generated by fusing two egg cell-specific promoters resulted in much higher efficiency of mutation in the T1 generation compared with the single promoters.
We report an efficient and economical method for remote δ C(sp
)-H heteroarylation of free aliphatic alcohols using a hypervalent iodine PFBI-OH oxidant under photoredox catalysis. The reaction ...sequence involves
alcoholysis of PFBI-OH with alcohol, generation of an alkoxy radical intermediate by SET reduction, 1,5-HAT, and Minisci-type C-C bond formation. This method uses a slight excess of alcohols, can facilitate reaction at δ methyl and methylene positions, and has been successfully applied to modification of complex drug molecules.
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