Pan-cancer whole-genome comparison of primary and metastatic solid tumours.

Metastatic cancer remains an almost inevitably lethal disease1-3. A better understanding of disease progression and response to therapies therefore remains of utmost importance. Here we characterize the genomic differences between early-stage untreated primary tumours and late-stage treated metastatic tumours using a harmonized pan-cancer analysis (or reanalysis) of two unpaired primary4 and metastatic5 cohorts of 7,108 whole-genome-sequenced tumours. Metastatic tumours in general have a lower intratumour heterogeneity and a conserved karyotype, displaying only a modest increase in mutations, although frequencies of structural variants are elevated overall. Furthermore, highly variable tumour-specific contributions of mutational footprints of endogenous (for example, SBS1 and APOBEC) and exogenous mutational processes (for example, platinum treatment) are present. The majority of cancer types had either moderate genomic differences (for example, lung adenocarcinoma) or highly consistent genomic portraits (for example, ovarian serous carcinoma) when comparing early-stage and late-stage disease. Breast, prostate, thyroid and kidney renal clear cell carcinomas and pancreatic neuroendocrine tumours are clear exceptions to the rule, displaying an extensive transformation of their genomic landscape in advanced stages. Exposure to treatment further scars the tumour genome and introduces an evolutionary bottleneck that selects for known therapy-resistant drivers in approximately half of treated patients. Our data showcase the potential of pan-cancer whole-genome analysis to identify distinctive features of late-stage tumours and provide a valuable resource to further investigate the biological basis of cancer and resistance to therapies.

Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.

The with-no-lysine kinase 4 (WNK4)-sterile 20/SPS-1-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway mediates activating phosphorylation of the furosemide-sensitive Na+-K+-2Cl- cotransporter (NKCC2) and the thiazide-sensitive NaCl cotransporter (NCC). The commonly used pT96/pT101-pNKCC2 antibody cross-reacts with pT53-NCC in mice on the C57BL/6 background due to a five amino acid deletion. We generated a new C57BL/6-specific pNKCC2 antibody (anti-pT96-NKCC2) and tested the hypothesis that the WNK4-SPAK/OSR1 pathway strongly regulates the phosphorylation of NCC but not NKCC2. In C57BL/6 mice, anti-pT96-NKCC2 detected pNKCC2 and did not cross-react with NCC. Abundances of pT96-NKCC2 and pT53-NCC were evaluated in Wnk4-/-, Osr1-/-, Spak-/-, and Osr1-/-/Spak-/- mice and in several models of the disease familial hyperkalemic hypertension (FHHt) in which the CUL3-KLHL3 ubiquitin ligase complex that promotes WNK4 degradation is dysregulated (Cul3+/-/Δ9, Klhl3-/-, and Klhl3R528H/R528H). All mice were on the C57BL/6 background. In Wnk4-/- mice, pT53-NCC was almost absent but pT96-NKCC2 was only slightly lower. pT53-NCC was almost absent in Spak-/- and Osr1-/-/Spak-/- mice, but pT96-NKCC2 abundance did not differ from controls. pT96-NKCC2/total NKCC2 was slightly lower in Osr1-/- and Osr1-/-/Spak-/- mice. WNK4 expression colocalized not only with NCC but also with NKCC2 in Klhl3-/- mice, but pT96-NKCC2 abundance was unchanged. Consistent with this, furosemide-induced urinary Na+ excretion following thiazide treatment was similar between Klhl3-/- and controls. pT96-NKCC2 abundance was also unchanged in the other FHHt mouse models. Our data show that disruption of the WNK4-SPAK/OSR1 pathway only mildly affects NKCC2 phosphorylation, suggesting a role for other kinases in NKCC2 activation. In FHHt models NKCC2 phosphorylation is unchanged despite higher WNK4 abundance, explaining the thiazide sensitivity of FHHt.NEW & NOTEWORTHY The renal cation cotransporters NCC and NKCC2 are activated following phosphorylation mediated by the WNK4-SPAK/OSR1 pathway. While disruption of this pathway strongly affects NCC activity, effects on NKCC2 activity are unclear since the commonly used phospho-NKCC2 antibody was recently reported to cross-react with phospho-NCC in mice on the C57BL/6 background. Using a new phospho-NKCC2 antibody specific for C57BL/6, we show that inhibition or activation of the WNK4-SPAK/OSR1 pathway in mice only mildly affects NKCC2 phosphorylation.

The exit of nanoparticles from solid tumours.

Nanoparticles enter tumours through endothelial cells, gaps or other mechanisms, but how they exit is unclear. The current paradigm states that collapsed tumour lymphatic vessels impair the exit of nanoparticles and lead to enhanced retention. Here we show that nanoparticles exit the tumour through the lymphatic vessels within or surrounding the tumour. The dominant lymphatic exit mechanism depends on the nanoparticle size. Nanoparticles that exit the tumour through the lymphatics are returned to the blood system, allowing them to recirculate and interact with the tumour in another pass. Our results enable us to define a mechanism of nanoparticle delivery to solid tumours alternative to the enhanced permeability and retention effect. We call this mechanism the active transport and retention principle. This delivery principle provides a new framework to engineer nanomedicines for cancer treatment and detection.

A waste-to-wealth conversion of plastic bottles into effective carbon-based adsorbents for removal of tetracycline antibiotic from water.

Currently, plastic waste and antibiotic wastewater are two of the most critical environmental problems, calling for urgent measures to take. A waste-to-wealth strategy for the conversion of polyethylene terephthalate (PET) plastic bottles into value-added materials such as carbon composite is highly recommended to clean wastewater contaminated by antibiotics. Inspired by this idea, we develop a novel PET-AC-ZFO composite by incorporating PET plastic-derived KOH-activated carbon (AC) with ZnFe2O4 (ZFO) particles for adsorptive removal of tetracycline (TTC). PET-derived carbon (PET-C), KOH-activated PET-derived carbon (PET-AC), and PET-AC-ZFO were characterized using physicochemical analyses. Central composite design (CCD) was used to obtain a quadratic model by TTC concentration (K), adsorbent dosage (L), and pH (M). PET-AC-ZFO possessed micropores (d ≈ 2 nm) and exceptionally high surface area of 1110 m2 g-1. Nearly 90% TTC could be removed by PET-AC-ZFO composite. Bangham kinetic and Langmuir isotherm were two most fitted models. Theoretical maximum TTC adsorption capacity was 45.1 mg g-1. This study suggested the role of hydrogen bonds, pore-filling interactions, and π-π interactions as the main interactions of the adsorption process. Thus, a strategy for conversion of PET bottles into PET-AC-ZFO can contribute to both plastic recycling and antibiotic wastewater mitigation.

Toward Predicting Nanoparticle Distribution in Heterogeneous Tumor Tissues.

Nanobio interaction studies have generated a significant amount of data. An important next step is to organize the data and design computational techniques to analyze the nanobio interactions. Here we developed a computational technique to correlate the nanoparticle spatial distribution within heterogeneous solid tumors. This approach led to greater than 88% predictive accuracy of nanoparticle location within a tumor tissue. This proof-of-concept study shows that tumor heterogeneity might be defined computationally by the patterns of biological structures within the tissue, enabling the identification of tumor patterns for nanoparticle accumulation.

Atomic-Scale Mechanism of Platinum Catalyst Restructuring under a Pressure of Reactant Gas.

Heterogeneous catalysis is key for chemical transformations. Understanding how catalysts' active sites dynamically evolve at the atomic scale under reaction conditions is a prerequisite for accurately determining catalytic mechanisms and predictably developing catalysts. We combine in situ time-dependent scanning tunneling microscopy observations and machine-learning-accelerated first-principles atomistic simulations to uncover the mechanism of restructuring of Pt catalysts under a pressure of carbon monoxide (CO). We show that a high CO coverage at a Pt step edge triggers the formation of atomic protrusions of low-coordination Pt atoms, which then detach from the step edge to create sub-nano-islands on the terraces, where under-coordinated sites are stabilized by the CO adsorbates. The fast and accurate machine-learning potential is key to enabling the exploration of tens of thousands of configurations for the CO-covered restructuring catalyst. These studies open an avenue to achieve an atomic-scale understanding of the structural dynamics of more complex metal nanoparticle catalysts under reaction conditions.

Insights into the synthesis strategies of plant-derived cyclotides.

Cyclotides are plant peptides characterized with a head-to-tail cyclized backbone and three interlocking disulfide bonds, known as a cyclic cysteine knot. Despite the variations in cyclotides peptide sequences, this core structure is conserved, underlying their most useful feature: stability against thermal and chemical breakdown. Cyclotides are the only natural peptides known to date that are orally bioavailable and able to cross cell membranes. Cyclotides also display bioactivities that have been exploited and expanded to develop as potential therapeutic reagents for a wide range of conditions (e.g., HIV, inflammatory conditions, multiple sclerosis, etc.). As such, in vitro production of cyclotides is of the utmost importance since it could assist further research on this peptide class, specifically the structure-activity relationship and its mechanism of action. The information obtained could be utilized to assist drug development and optimization. Here, we discuss several strategies for the synthesis of cyclotides using both chemical and biological routes.

Green synthesis of ZnFe2O4@ZnO nanocomposites using Chrysanthemum spp. floral waste for photocatalytic dye degradation.

The occurrence of textile dyeing wastewater discharged into the environment has been recently increasing, resulting in harmful effects on living organisms and human health. The use of green nanoparticles for water decontamination has received much attention. Floral waste can be extracted with the release of natural compounds, which act as reducing and stabilizing agents during the biosynthesis of nanoparticles. Herein, we report the utilization of Chrysanthemum spp. floral waste extract to synthesize green ZnFe2O4@ZnO (ZFOZx) nanocomposites for the photocatalytic degradation of Congo red under solar light irradiation. The various molar ratio of ZnFe2O4 (0-50%) was incorporated into ZnO nanoparticles. The surface area of green ZFOZx nanocomposites was found to increase (7.41-42.66 m2 g-1) while their band gap energy decreased from 1.98 eV to 1.92 eV. Moreover, the results exhibited the highest Congo red dye degradation efficiency of 94.85% at a concentration of 5.0 mg L-1, and a catalyst dosage of 0.33 g L-1. The •O2- reactive species played a vital role in the photocatalytic degradation of Congo red dye. Green ZFOZ3 nanocomposites had good recyclability with at least three cycles, and an excellent stability. The germination results showed that wastewater treated by ZFOZ3 was safe enough for bean seed germination. We expect that this work contributes significantly to developing novel green bio-based nanomaterials for environmental remediation as well as reducing the harm caused by flower wastes.

Cullin 3 mutant causing familial hyperkalemic hypertension lacks normal activity in the kidney.

Mutations in the ubiquitin ligase scaffold protein cullin 3 (CUL3) cause the disease familial hyperkalemic hypertension (FHHt). We recently reported that in the kidney, aberrant mutant CUL3 (CUL3-Δ9) activity lowers the abundance of CUL3-Δ9 and Kelch-like 3, the CUL3 substrate adaptor for with-no-lysine kinase 4 (WNK4) and that this is mechanistically important. However, whether CUL3-Δ9 exerts additional effects on other targets that may alter renal function is unclear. Here, we sought to determine 1) whether CUL3-Δ9 expression can rescue the phenotype of renal tubule-specific Cul3 knockout mice, and 2) whether CUL3-Δ9 expression affects other CUL3 substrates. Using an inducible renal tubule-specific system, we studied two CUL3-Δ9-expressing mouse models: Cul3 knockout (Cul3-/-/Δ9) and Cul3 heterozygous background (Cul3+/-/Δ9, FHHt model). The effects of CUL3-Δ9 in these mice were compared with Cul3-/- and Cul3+/- mice. Similar to Cul3-/- mice, Cul3-/-/Δ9 mice displayed polyuria with loss of aquaporin 2 and collecting duct injury; proximal tubule injury also occurred. CUL3-Δ9 did not promote degradation of two CUL3 targets that accumulate in the Cul3-/- kidney: high-molecular-weight (HMW) cyclin E and NAD(P)H:quinone oxidoreductase 1 (NQO1) [a surrogate for the CUL3-Kelch-like ECH-associated protein 1 (KEAP1) substrate nuclear factor erythroid-2-related factor 2]. Since CUL3-Δ9 expression cannot rescue the Cul3-/- phenotype, our data suggest that CUL3-Δ9 cannot normally function in ubiquitin ligase complexes. In Cul3+/-/Δ9 mice, KEAP1 abundance did not differ but NQO1 abundance was higher, suggesting adaptor sequestration by CUL3-Δ9 in vivo. Together, our results provide evidence that in the kidney, CUL3-Δ9 completely lacks normal activity and can trap CUL3 substrate adaptors in inactive complexes.NEW & NOTEWORTHY CUL3 mutation (CUL3-Δ9) causes familial hyperkalemic hypertension (FHHt) by reducing adaptor KLHL3, impairing substrate WNK4 degradation. Whether CUL3-Δ9 affects other targets in kidneys remains unclear. We found that CUL3-Δ9 cannot degrade two CUL3 targets, cyclin E and nuclear factor erythroid-2-related factor 2 (NRF2; using a surrogate marker NQO1), or rescue injury or polyuria caused by Cul3 disruption. In an FHHt model, CUL3-Δ9 impaired NRF2 degradation without reduction of its adaptor KEAP1. Our data provide additional insights into CUL3-Δ9 function in the kidney.

Facile synthesis of CoFe2O4@MIL-53(Al) nanocomposite for fast dye removal: Adsorption models, optimization and recyclability.

The global occurrence of textile dyes pollution has recently emerged, posing a serious threat to ecological systems. To abate dye contamination, we here developed a novel magnetic porous CoFe2O4@MIL-53(Al) nanocomposite by incorporating magnetic CoFe2O4 nanoparticles with MIL-53(Al) metal-organic framework. This nanocomposite possessed a surface area of 197.144 m2 g-1 and a pore volume of 0.413 cm3 g-1. The effect of contact time (5-120 min), concentration (5-50 mg L-1), dosage (0.1-1.0 g L-1), and pH (2-10) on Congo red adsorption was clarified. CoFe2O4@MIL-53(Al) could remove 95.85% of Cong red dye from water with an accelerated kinetic rate of 0.6544 min-1 within 10 min. The kinetic and isotherm models showed the predominance of Bangham and Temkin. According to Langmuir, the maximum uptake capacities of CoFe2O4@MIL-53(Al), CoFe2O4, and MIL-53(Al) adsorbents were 43.768, 17.982, and 15.295 mg g-1, respectively. CoFe2O4@MIL-53(Al) was selected to optimize Cong red treatment using Box-Behnken experimental design. The outcomes showed that CoFe2O4@MIL-53(Al) achieved the highest experimental uptake capacity of 35.919 mg g-1 at concentration (29.966 mg L-1), time (14.926 min), and dosage (0.486 g L-1). CoFe2O4@MIL-53(Al) could treat dye mixture (methylene blue, methyl orange, Congo red, malachite green, and crystal violet) with an outstanding removal efficiency of 81.24% for 30 min, and could be reused up to five cycles. Therefore, novel recyclable and stable CoFe2O4@MIL-53(Al) is recommended to integrate well with real dye treatments systems.

Asymmetric dimerization of adenosine deaminase acting on RNA facilitates substrate recognition.

Adenosine deaminases acting on RNA (ADARs) are enzymes that convert adenosine to inosine in duplex RNA, a modification that exhibits a multitude of effects on RNA structure and function. Recent studies have identified ADAR1 as a potential cancer therapeutic target. ADARs are also important in the development of directed RNA editing therapeutics. A comprehensive understanding of the molecular mechanism of the ADAR reaction will advance efforts to develop ADAR inhibitors and new tools for directed RNA editing. Here we report the X-ray crystal structure of a fragment of human ADAR2 comprising its deaminase domain and double stranded RNA binding domain 2 (dsRBD2) bound to an RNA duplex as an asymmetric homodimer. We identified a highly conserved ADAR dimerization interface and validated the importance of these sequence elements on dimer formation via gel mobility shift assays and size exclusion chromatography. We also show that mutation in the dimerization interface inhibits editing in an RNA substrate-dependent manner for both ADAR1 and ADAR2.

Quadcopter UAVs Extended States/Disturbance Observer-Based Nonlinear Robust Backstepping Control.

A trajectory tracking control for quadcopter unmanned aerial vehicle (UAV) based on a nonlinear robust backstepping algorithm and extended state/disturbance observer (ESDO) is presented in this paper. To obtain robust attitude stabilization and superior performance of three-dimension position tracking control, the construction of the proposed algorithm can be separated into three parts. First, a mathematical model of UAV negatively influenced by exogenous disturbances is established. Following, an extended state/disturbance observer using a general second-order model is designed to approximate undesirable influences of perturbations on the UAVs dynamics. Finally, a nonlinear robust controller is constructed by an integration of the nominal backstepping technique with ESDO to enhance the performance of attitude and position control mode. Robust stability of the closed-loop disturbed system is obtained and guaranteed through the Lyapunov theorem without precise knowledge of the upper bound condition of perturbations. Lastly, a numerical simulation is carried out and compared with other previous controllers to demonstrate the great advantage and effectiveness of the proposed control method.

Formation, antimicrobial activity, and biomedical performance of plant-based nanoparticles: a review.

Because many engineered nanoparticles are toxic, there is a need for methods to fabricate safe nanoparticles such as plant-based nanoparticles. Indeed, plant extracts contain flavonoids, amino acids, proteins, polysaccharides, enzymes, polyphenols, steroids, and reducing sugars that facilitate the reduction, formation, and stabilization of nanoparticles. Moreover, synthesizing nanoparticles from plant extracts is fast, safe, and cost-effective because it does not consume much energy, and non-toxic derivatives are generated. These nanoparticles have diverse and unique properties of interest for applications in many fields. Here, we review the synthesis of metal/metal oxide nanoparticles with plant extracts. These nanoparticles display antibacterial, antifungal, anticancer, and antioxidant properties. Plant-based nanoparticles are also useful for medical diagnosis and drug delivery.

Occurrence, toxicity and adsorptive removal of the chloramphenicol antibiotic in water: a review.

Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, hydrogen bonding, and electrostatic interactions. We also discuss isotherms, kinetics, thermodynamic data, selection of eluents, desorption efficiency, and regeneration of adsorbents. Porous carbon-based adsorbents exhibit excellent adsorption capacities of 500-1240 mg g-1. Most adsorbents can be reused over at least four cycles.

Single-Atom High-Temperature Catalysis on a Rh1O5 Cluster for Production of Syngas from Methane.

Single-atom catalysts are a relatively new type of catalyst active for numerous reactions but mainly for chemical transformations performed at low or intermediate temperatures. Here we report that singly dispersed Rh1O5 clusters on TiO2 can catalyze the partial oxidation of methane (POM) at high temperatures with a selectivity of 97% for producing syngas (CO + H2) and high activity with a long catalytic durability at 650 °C. The long durability results from the substitution of a Ti atom of the TiO2 surface lattice by Rh1, which forms a singly dispersed Rh1 atom coordinating with five oxygen atoms (Rh1O5) and an undercoordinated environment but with nearly saturated bonding with oxygen atoms. Computational studies show the back-donation of electrons from the dz2 orbital of the singly dispersed Rh1 atom to the unoccupied orbital of adsorbed CHn (n > 1) results in the charge depletion of the Rh1 atom and a strong binding of CHn to Rh1. This strong binding decreases the barrier for activating C-H, thus leading to high activity of Rh1/TiO2. A cationic Rh1 single atom anchored on TiO2 exhibits a weak binding to atomic carbon, in contrast to the strong binding of the metallic Rh surface to atomic carbon. The weak binding of atomic carbon to Rh1 atoms and the spatial isolation of Rh1 on TiO2 prevent atomic carbon from coupling on Rh1/TiO2 to form carbon layers, making Rh1/TiO2 resistant to carbon deposition than supported metal catalysts for POM. The highly active, selective, and durable high-temperature single-atom catalysis performed at 650 °C demonstrates an avenue of application of single-atom catalysis to chemical transformations at high temperatures.

Understanding Catalyst Surfaces during Catalysis through Near Ambient Pressure X-ray Photoelectron Spectroscopy.

Heterogeneous catalysis occurs on the surface of a catalyst particle in a gas or liquid environment of reactants. The surface of the catalyst particle acts as an active chemical agent directly participating in a chemical reaction performed at a solid-gas or solid-liquid interface. Thus, authentic surface chemistry and the structure of a catalyst particle during catalysis are key descriptors for understanding catalytic performance of this catalyst. However, identification of the authentic surface of a catalyst particle during catalysis is not a simple task. We are far from knowing the fact. Photoelectron spectroscopy is one of the main techniques for characterizing surface of a catalyst since it's a surface sensitive technique. When used to track the surface of a catalyst particle at relatively high temperature in gas phase in the torr pressure range, it is called near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) or AP-XPS for simplicity. In the last several years, AP-XPS has been used to observe surface chemistry of catalysts of single crystals and nanoparticles of metal, metal oxide, and carbide. In this review, instrumentation of the near ambient pressure X-ray photoelectron spectrometers and observation of catalyst surfaces in gases phase under reaction conditions and during catalysis with AP-XPS are discussed with the following objectives: (1) to present how the surface of a catalyst particle can be characterized in gas phase, (2) to interpret how surface chemistries observed during catalysis are correlated with measured catalytic performances, (3) to demonstrate how the uncovered correlations between surface structures and catalytic performances help to understand catalytic mechanisms at a molecular level, and (4) to discuss challenges and prospects of using AP-XPS to explore the authentic surface of a catalyst under a condition near to an industrial catalytic condition. This review focuses on the application of AP-XPS to studies of catalysis and how the insights gained from AP-XPS studies can be used to achieve fundamental understanding of the catalytic mechanism at a molecular level.

Atomic-Scale Structure and Catalysis on Positively Charged Bimetallic Sites for Generation of H2.

Here, we report that a cationic bimetallic site consisting of one Pd and three Zn atoms (Pd1Zn3) supported on ZnO (Pd1Zn3/ZnO) exhibits an extraordinarily high catalytic activity for the generation of H2 through methanol partial oxidation (MPO) that is 2-3 orders of magnitude higher than that of a metallic Pd-Zn site on Pd-Zn nanoalloy (Pd-Zn/ZnO). Computational studies uncovered that the positively charged Pd atom of the subnanometer Pd1Zn3 bimetallic site largely decreases the activation barrier for dehydrogenation of methanol as compared to a metallic Pd atom of Pd-Zn alloy, thus switching the rate-determining step of MPO from methanol dehydrogenation over a Pd-Zn alloy with high barrier to the O2 dissociation step on a cationic Pd1Zn3 site with a low barrier, which is supported by our kinetics studies. The significantly higher catalytic activity and selectivity for H2 production over a cationic bimetallic site suggest a new approach to design bimetallic catalysts.

Evaluation of a Liquid Biopsy Protocol using Ultra-Deep Massive Parallel Sequencing for Detecting and Quantifying Circulation Tumor DNA in Colorectal Cancer Patients.

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling. Here, we developed a LB protocol using ultra-deep massive parallel sequencing and validated its clinical performance for detection and quantification of actionable mutations in three major driver genes (KRAS, NRAS and BRAF). The assay showed a 92% concordance for mutation detection between plasma and paired tissues and great reliability in quantification of variant allele frequency.

Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity.

Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 h and retaining larger ones (50-100 nm) for over 5 weeks. The 50-100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.

Synergy of Single-Atom Ni1 and Ru1 Sites on CeO2 for Dry Reforming of CH4.

Heterogeneous catalysis performs on specific sites of a catalyst surface even if specific sites of many catalysts during catalysis could not be identified readily. Design of a catalyst by managing catalytic sites on an atomic scale is significant for tuning catalytic performance and offering high activity and selectivity at a relatively low temperature. Here, we report a synergy effect of two sets of single-atom sites (Ni1 and Ru1) anchored on the surface of a CeO2 nanorod, Ce0.95Ni0.025Ru0.025O2. The surface of this catalyst, Ce0.95Ni0.025Ru0.025O2, consists of two sets of single-atom sites which are highly active for reforming CH4 using CO2 with a turnover rate of producing 73.6 H2 molecules on each site per second at 560 °C. Selectivity for producing H2 at this temperature is 98.5%. The single-atom sites Ni1 and Ru1 anchored on the CeO2 surface of Ce0.95Ni0.025Ru0.025O2 remain singly dispersed and in a cationic state during catalysis up to 600 °C. The two sets of single-atom sites play a synergistic role, evidenced by lower apparent activation barrier and higher turnover rate for production of H2 and CO on Ce0.95Ni0.025Ru0.025O2 in contrast to Ce0.95Ni0.05O2 with only Ni1 single-atom sites and Ce0.95Ru0.05O2 with only Ru1 single-atom sites. Computational studies suggest a molecular mechanism for the observed synergy effects, which originate at (1) the different roles of Ni1 and Ru1 sites in terms of activations of CH4 to form CO on a Ni1 site and dissociation of CO2 to CO on a Ru1 site, respectively and (2) the sequential role in terms of first forming H atoms through activation of CH4 on a Ni1 site and then coupling of H atoms to form H2 on a Ru1 site. These synergistic effects of the two sets of single-atom sites on the same surface demonstrated a new method for designing a catalyst with high activity and selectivity at a relatively low temperature.