Summary Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient ...overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA.
Nitrates are widely used as fertilizer and oxidizing agents. Commercial nitrate production from nitrogen involves high‐temperature‐high‐pressure multi‐step processes. Therefore, an alternative ...nitrate production method under ambient environment is of importance. Herein, an electrochemical nitrogen oxidation reaction (NOR) approach is developed to produce nitrate catalyzed by ZnFexCo2−xO4 spinel oxides. Theoretical and experimental results show Fe aids the formation of the first N−O bond on the *N site, while high oxidation state Co assists in stabilizing the absorbed OH− for the generation of the second and third N−O bonds. Owing to the concerted catalysis, the ZnFe0.4Co1.6O4 oxide demonstrates the highest nitrate production rate of 130±12 μmol h−1 gMO−1 at an applied potential of 1.6 V versus the reversible hydrogen electrode (RHE).
Spinel tap: Nitrate is prepared by direct electrochemical oxidation of nitrogen on ZnFexCo2−xO4 spinel oxides in alkaline electrolyte. The combined effect of Fe and Co in octahedral sites is found advantageous for nitrate formation and spinel ZnFe0.4Co1.6O4 exhibits the highest nitrate yield.
Mn–Co containing spinel oxides are promising, low‐cost electrocatalysts for the oxygen reduction reaction (ORR). Most studies are devoted to the design of porous Mn–Co spinels or to strongly coupled ...hybrids (e.g., MnCo2O4/N‐doped‐rmGO) to maximize the mass efficiency. The lack of analyses by metal oxide intrinsic activity (activity normalized to catalysts' surface area) hinders the development of fundamental understanding of the physicochemical principles behind the catalytic activities. A systematic study on the composition dependence of ORR in ZnCoxMn2−xO4 (x = 0.0–2.0) spinel is presented here with special attention to the role of edge sharing CoxMn1−xO6 octahedra in the spinel structure. The ORR specific activity of ZnCoxMn2−xO4 spans across a potential window of 200 mV, indicating an activity difference of ≈3 orders of magnitude. The curve of composition‐dependent ORR specific activity as a function of Co substitution exhibits a volcano shape with an optimum Mn/Co ratio of 0.43. It is revealed that the modulated eg occupancy of active Mn cations (0.3–0.9), as a consequence of the superexchange effect between edge sharing CoO6 and MnO6, reflects the ORR activity of edge sharing CoxMn1−xO6 octahedra in the ZnCoxMn2−xO4 spinel oxide. These findings offer crucial insights in designing spinel oxide catalysts with fine‐tuned eg occupancy for efficient catalysis.
The superexchange interaction between CoO6 and MnO6 in spinel structured ZnCoxMn2−xO4 has a significant influence on its activity toward the oxygen reduction reaction. With Co substitution, the evolution of the Mn antibonding orbital state in the edge‐sharing CoxMn1−xO6 octahedron is rearranged by the superexchange interaction.
We report the generation of stable and tunable electron bunches with very low absolute energy spread (ΔE ≈ 5 MeV) accelerated in laser wakefields via injection and trapping at a sharp downward ...density jump produced by a shock front in a supersonic gas flow. The peak of the highly stable and reproducible electron energy spectrum was tuned over more than 1 order of magnitude, containing a charge of 1-100 pC and a charge per energy interval of more than 10 pC/MeV. Laser-plasma electron acceleration with Ti:sapphire lasers using this novel injection mechanism provides high-quality electron bunches tailored for applications.
Viral exposure—the complete history
In addition to causing illness, viruses leave indelible footprints behind, because infection permanently alters the immune system. Blood tests that detect ...antiviral antibodies can provide information about both past and present viral exposures. Typically, such tests measure only one virus at a time. Using a synthetic representation of all human viral peptides, Xu
et al.
developed a blood test that identifies antibodies against all known human viruses. They studied blood samples from nearly 600 people of differing ages and geographic locations and found that most had been exposed to about 10 viral species over their lifetime. Despite differences in the rates of exposure to specific viruses, the antibody responses in most individuals targeted the same viral epitopes.
Science
, this issue
10.1126/science.aaa0698
A complete history of viral exposure over a lifetime can be deduced from a drop of blood.
Introduction
The collection of viruses found to infect humans can have profound effects on human health. In addition to directly causing acute or chronic illness, viral infection can alter host immunity in more subtle ways, leaving an indelible footprint on the immune system. This interplay between virome and host immunity has been implicated in the pathogenesis of complex diseases such as type 1 diabetes, inflammatory bowel disease, and asthma. Despite the growing appreciation for the importance of interactions between the virome and host, a comprehensive method to systematically characterize these interactions has yet to be developed.
Rationale
Current serological methods to detect viral infections are predominantly limited to testing one pathogen at a time and are therefore used primarily to address specific clinical hypotheses. A method that could simultaneously detect responses to all human viruses would allow hypothesis-free analysis to detect associations between past viral infections and particular diseases or population structures. Humoral responses to infection typically arise within 10 to 14 days of initial exposure and can persist over years or decades, thus providing a rich source of the history of pathogen encounters. In this work, we present VirScan, a high-throughput method that allows comprehensive analysis of antiviral antibodies in human sera. VirScan uses DNA microarray synthesis and bacteriophage display to create a uniform, synthetic representation of peptide epitopes comprising the human virome. Immunoprecipitation and high-throughput DNA sequencing reveal the peptides recognized by antibodies in the sample. The analysis requires less than 1 μl of blood.
Results
We screened sera from 569 human donors across four continents, assaying a total of over 10
8
antibody-peptide interactions for reactivity to 206 human viral species and >1000 strains. We found that VirScan’s performance in detecting known infections and distinguishing between exposures to related viruses is comparable to that of classical serum antibody tests for single viruses. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Our approach maps antibody targets at 56–amino acid resolution, and our results nearly double the number of previously established viral B cell epitopes. Although rates of specific virus exposure varied depending on age, HIV status, and geographic location of the donor, we observed strong similarities in antibody responses across individuals. In particular, we found multiple instances of single peptides that were recurrently recognized by antibodies in the vast majority of donors. We performed tiling mutagenesis and found that these antibody responses targeted substantially conserved “public epitopes” for each virus, suggesting that antibodies with highly similar specificities, and possibly structures, are elicited across individuals.
Conclusion
VirScan is a method that enables human virome-wide exploration, at the epitope level, of immune responses in large numbers of individuals. We have demonstrated its effectiveness for determining viral exposure and characterizing viral B cell epitopes in high throughput and at high resolution. Our preliminary studies have revealed intriguing general properties of the human immune system, both at the individual and the population scale. VirScan may prove to be an important tool for uncovering the effect of host-virome interactions on human health and disease and could easily be expanded to include new viruses as they are discovered, as well as other human pathogens, such as bacteria, fungi, and protozoa.
Systematic viral epitope scanning (VirScan).
This method allows comprehensive analysis of antiviral antibodies in human sera. VirScan combines DNA microarray synthesis and bacteriophage display to create a uniform, synthetic representation of peptide epitopes comprising the human virome. Immunoprecipitation and high-throughput DNA sequencing reveal the peptides recognized by antibodies in the sample. The color of each cell in the heatmap depicts the relative number of antigenic epitopes detected for a virus (rows) in each sample (columns).
The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10
8
antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved “public epitopes” for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system.
Electrochemical CO2 reduction relies on the availability of highly efficient and selective catalysts. Herein, we report a general strategy to boost the activity of metal–organic frameworks (MOFs) ...towards CO2 reduction via ligand doping. A strong electron‐donating molecule of 1,10‐phenanthroline was doped into Zn‐based MOFs of zeolitic imidazolate framework‐8 (ZIF‐8) as CO2 reduction electrocatalyst. Experimental and theoretical evidences reveal that the electron‐donating nature of phenanthroline enables a charge transfer, which induces adjacent active sites at the sp2 C atoms in the imidazole ligand possessing more electrons, and facilitates the generation of *COOH, hence leading to improved activity and Faradaic efficiency towards CO production.
Organic doping: Electron‐donating 1,10‐phenanthroline molecules are doped into ZIF‐8 to form a CO2 reduction electrocatalyst. The dopant enables charge transfer to the sp2 C atom active site in the imidazole ligand and thus facilitates the generation of *COOH, hence leading to improved activity and Faradaic efficiency towards CO production.
The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this ...study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor κB (NF-κB) activation. On the other hand, we also found that the adriamycin-activated NF-κB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-κB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-κB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-κB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component.
direct energy method under a monotonicity condition on the tangential velocity field instead of using the Crocco transformation. Precisely, we firstly investigate the linearized Prandtl equation in ...some weighted Sobolev spaces when the tangential velocity of the background state is monotonic in the normal variable. Then to cope with the loss of regularity of the perturbation with respect to the background state due to the degeneracy of the equation, we apply the Nash-Moser-H>ö
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