Abstract
Severe events of wintertime particulate air pollution in Beijing (winter haze) are associated with high relative humidity (RH) and fast production of particulate sulfate from the oxidation ...of sulfur dioxide (SO
2
) emitted by coal combustion. There has been considerable debate regarding the mechanism for SO
2
oxidation. Here we show evidence from field observations of a haze event that rapid oxidation of SO
2
by nitrogen dioxide (NO
2
) and nitrous acid (HONO) takes place, the latter producing nitrous oxide (N
2
O). Sulfate shifts to larger particle sizes during the event, indicative of fog/cloud processing. Fog and cloud readily form under winter haze conditions, leading to high liquid water contents with high pH (>5.5) from elevated ammonia. Such conditions enable fast aqueous-phase oxidation of SO
2
by NO
2
, producing HONO which can in turn oxidize SO
2
to yield N
2
O.This mechanism could provide an explanation for sulfate formation under some winter haze conditions.
Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of ...WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina–heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.
Land use change is affected by many driving factors such as the economy, population, and government policy. This study investigated the relationship between government policy and land use change to ...develop an understanding applicable to the formulation of strategies for sustainable land use. The Lijiang River Basin in the Guangxi Zhuang Autonomous Region in southern China was selected for this study. The predicted characteristics of land use change were explored using the CLUE-S numerical model and logistic regression. Using Landsat remote sensing imagery as source data, we simulated the tendency of land use change from 1993 to 2020 under two scenarios: a Natural Growth Scenario (NS) and a Government Intervention Scenario (GS), and we analyzed the possible social driving factors. The results revealed that from 1993 to 2015, both construction and cultivated land have shown a tendency of areal increase. Water and woodland areas both decreased from 1993 to 2006 but then they increased dramatically from 2006 to 2015. Shrubland areas increased from 1993 to 2006 but decreased slightly from 2006 to 2015. The CLUE-S model was used to predict the spatial patterns of land use for 2020. It showed that under the NS, the areas of construction and cultivated land increased, while the areas of other land uses decreased. Under the GS, the areas of construction land, woodland, cultivated land, and water all increased, while the areas of the others declined. Furthermore, the area of woodland decreased for every county under the NS, but areas of woodland expansion were located in Lingchuan and Lingui counties under the GS. Hotspots of cultivated land occurred in Lingchuan County under the NS and in Xingan County under the GS. Water area decreased in every county under the NS, whereas increases in water areas occurred in Lingchuan and Guilin counties under the GS. Construction land expanded in Lingchuan County under the NS and in Guilin County under the GS. The Returning Farmland to Forest Program could be considered a successful addition to the eco-environmental policies implemented in the Lijiang River Basin.
•Discover the spatiotemporal distribution of recent land use change in the Lijiang River Basin in China.•Predict the spatial patterns of land use for 2020 under two scenarios using the CLUE-S model and logistic regression.•Investigate the influence of Returning Farmland to Forest Program on the tendency of land use change.
The effectiveness of immune responses depends on the precision of stimulus-responsive gene expression programs. Cells specify which genes to express by activating stimulus-specific combinations of ...stimulus-induced transcription factors (TFs). Their activities are decoded by a gene regulatory strategy (GRS) associated with each response gene. Here, we examined whether the GRSs of target genes may be inferred from stimulus-response (input-output) datasets, which remains an unresolved model-identifiability challenge. We developed a mechanistic modeling framework and computational workflow to determine the identifiability of all possible combinations of synergistic (AND) or non-synergistic (OR) GRSs involving three transcription factors. Considering different sets of perturbations for stimulus-response studies, we found that two thirds of GRSs are easily distinguishable but that substantially more quantitative data is required to distinguish the remaining third. To enhance the accuracy of the inference with timecourse experimental data, we developed an advanced error model that avoids error overestimates by distinguishing between value and temporal error. Incorporating this error model into a Bayesian framework, we show that GRS models can be identified for individual genes by considering multiple datasets. Our analysis rationalizes the allocation of experimental resources by identifying most informative TF stimulation conditions. Applying this computational workflow to experimental data of immune response genes in macrophages, we found that a much greater fraction of genes are combinatorially controlled than previously reported by considering compensation among transcription factors. Specifically, we revealed that a group of known NFκB target genes may also be regulated by IRF3, which is supported by chromatin immuno-precipitation analysis. Our study provides a computational workflow for designing and interpreting stimulus-response gene expression studies to identify underlying gene regulatory strategies and further a mechanistic understanding.
Oregano essential oil (OEO), as a natural antimicrobial, has gained increased interest from food researchers and manufacturers. However, a few studies have investigated its possible antibacterial ...effects against
Staphylococcus aureus
using the proteomic tool. The present study aimed to explore the antibacterial effect and mechanism of a carvacrol-rich OEO extracted from
Origanum vulgare
“Hot & Spicy” on the inactivation of
S. aureus
. The gas chromatography–mass spectrometry analysis of the OEO allowed the detection of 27 compounds; the major constituent was carvacrol (84.38% of total compounds). The average diameter of the inhibitory zone (DIZ) value was 29.10 mm, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OEO against
S. aureus
were 0.125 and 0.25 mg/mL, respectively. The growth curve assay indicated that the OEO prolonged the lag phase of
S. aureus
. The decrease in cell viability, changes in the integrity of cell membrane, and abnormal cell morphology further reflected the cell damage of
S. aureus
caused by the OEO. In addition, a label-free proteomic analysis was applied to analyze the regulatory networks of
S. aureus
in response to 1/2 MIC OEO-treatment stress. Of the 56 differentially expressed proteins (DEPs) identified, 26 were significantly upregulated and 30 downregulated. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEPs were mainly involved in pathways of ribosomes; valine, leucine, and isoleucine biosynthesis; and phenylalanine, tyrosine, and tryptophan biosynthesis, which suggested that the growth inhibition of
S. aureus
might be due to the disordered effect of the OEO on protein synthesis and amino acid metabolism. These findings deepened our understanding regarding
S. aureus
survival and metabolism responses to the OEO treatment and suggested that the carvacrol-rich OEO could be used in food production environments to effectively control
S. aureus.
When identifying differentially expressed genes between two conditions using human population RNA-seq samples, we found a phenomenon by permutation analysis: two popular bioinformatics methods, ...DESeq2 and edgeR, have unexpectedly high false discovery rates. Expanding the analysis to limma-voom, NOISeq, dearseq, and Wilcoxon rank-sum test, we found that FDR control is often failed except for the Wilcoxon rank-sum test. Particularly, the actual FDRs of DESeq2 and edgeR sometimes exceed 20% when the target FDR is 5%. Based on these results, for population-level RNA-seq studies with large sample sizes, we recommend the Wilcoxon rank-sum test.
SIRT6 belongs to the mammalian homologs of Sir2 histone NAD＋-dependent deacylase family. In rodents, SIRT6 deficiency leads to aging-associated degeneration of mesodermal tissues. It remains unknown ...whether human SIRT6 has a direct role in maintaining the homeostasis of mesodermal tissues. To this end, we generated SIRT6 knockout hu- man mesenchymal stem cells （hMSCs） by targeted gene editing. SIRT6-deficient hMSCs exhibited accelerated func- tional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs were predominately characterized by dysregulated redox metabolism and increased sen- sitivity to the oxidative stress. In addition, we found SIRT6 in a protein complex with both nuclear factor erythroid 2-related factor 2 （NRF2） and RNA polymerase II, which was required for the transactivation of NRF2-regulated an- tioxidant genes, including heme oxygenase 1 （HO-1）. Overexpression of HO-1 in SIRT6-null hMSCs rescued prema- ture cellular attrition. Our study uncovers a novel function of SIRT6 in maintaining hMSC homeostasis by serving as a NRF2 coactivator, which represents a new layer of regulation of oxidative stress-associated stem cell decay.
Metal electrodes with rough surfaces are often found to convert CO or CO2 to hydrocarbons and oxygenates with high selectivity and at high reaction rates in comparison with their smooth counterparts. ...The atomic-level morphology of a rough electrode is likely one key factor responsible for its comparatively high catalytic selectivity and activity. However, few methods are capable of probing the atomic-level structure of rough metal electrodes under electrocatalytic conditions. As a result, the nuances in the atomic-level surface morphology that control the catalytic characteristics of these electrodes have remained largely unexplored. Because the CO stretching frequency of atop-bound CO (COatop) depends on the coordination of the underlying metal atom, the IR spectrum of this reaction intermediate on the copper electrode could, in principle, provide structural information about the catalytic surface during electrolysis. However, other effects, such as dynamic dipole coupling, easily obscure the dependence of the frequency on the surface morphology. Further, in the limit of low COatop coverage, where coupling effects are small, the CO stretching frequencies of COatop on Cu(111) and Cu(100) facets are virtually identical. Therefore, on the basis of the CO stretching frequency, it is not straightforward to distinguish between these two ubiquitous surface facets, which exhibit vastly different CO reduction activities. Herein, we show that key features of the atomic-level surface morphology of rough copper electrodes can be inferred from the potential dependence of the line shape of the CO stretching band of COatop. Specifically, we compared two types of rough copper thin-film electrodes that are routinely employed in the context of surface-enhanced infrared absorption spectroscopy (SEIRAS). We found that copper films that are electrochemically deposited on Si-supported Au films (CuAu–Si) are poor catalysts for the reduction of CO to ethylene in comparison to copper films (Cu–Si) that are electrolessly deposited onto Si crystals. As quantified by differential electrochemical mass spectrometry (DEMS), the onset potential for ethylene is ∼200 ± 65 mV more cathodic for CuAu–Si than that for Cu–Si. To reveal the origin of the disparate catalytic properties of Cu–Si and CuAu–Si, we probed the surfaces of the electrodes with cyclic voltammetry (CV) and SEIRAS. The CV characterization suggests that the (111) surface facet predominates on CuAu–Si, whereas the (100) facet is more common on Cu–Si. SEIRAS reveals that the line shape of the CO stretching of COatop is composed of two bands that are attributable to COatop on terrace and defect sites. The different surface structures manifest themselves in the form of starkly different potential dependences of the line shape of the CO stretching mode of COatop on the two types of electrodes. With a simple Boltzmann model that considers the different adsorption energies of COatop on terrace and defect sites, and the resulting COatop populations on terrace and defect sites, we deduced that the observed electrode-specific potential dependence of the line shape is consistent with the presence of different predominant terrace sites on the two types of films. This strategy for assessing the atomic-level morphology is not restricted to SEIRAS but could also be applied to the CO stretching bands recorded with surface-enhanced Raman spectroscopy (SERS), which is suitable for probing a wide range of rough copper electrodes. Therefore, with this work, we establish the potential dependence of the CO stretching band of COatop as a probe of the atomic-level surface structure of rough metal electrodes under electrochemical conditions. When it is coupled with complementary techniques, this methodology provides essential structural information for further improvement in the reaction selectivity of rough metal electrodes.
Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. ...It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1β and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis.
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell ...transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders.
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