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Heterogeneous catalysts are widely used to promote chemical reactions. Although it is known that chemical reactions usually happen on catalyst surfaces, only specific surface sites have high catalytic activity. Thus, identifying active sites and maximizing their presence lies at the heart of catalysis research 1 – 4 , in which the classic model is to categorize active sites in terms of distinct surface motifs, such as terraces and steps 1 , 5 – 10 . However, such a simple categorization often leads to orders of magnitude errors in catalyst activity predictions and qualitative uncertainties of active sites 7 , 8 , 11 , 12 , thus limiting opportunities for catalyst design. Here, using stepped Pt(111) surfaces and the electrochemical oxygen reduction reaction (ORR) as examples, we demonstrate that the root cause of larger errors and uncertainties is a simplified categorization that overlooks atomic site-specific reactivity driven by surface stress release. Specifically, surface stress release at steps introduces inhomogeneous strain fields, with up to 5.5% compression, leading to distinct electronic structures and reactivity for terrace atoms with identical local coordination, and resulting in atomic site-specific enhancement of ORR activity. For the terrace atoms flanking both sides of the step edge, the enhancement is up to 50 times higher than that of the atoms in the middle of the terrace, which permits control of ORR reactivity by either varying terrace widths or controlling external stress. Thus, the discovery of the above synergy provides a new perspective for both fundamental understanding of catalytically active atomic sites and design principles of heterogeneous catalysts. Stress release at stepped platinum surfaces is shown to influence the strain experienced by atoms near the steps, resulting in effects on the catalytic activity of the whole surface.

Copper ions exchanged into zeolites are active for the selective catalytic reduction (SCR) of nitrogen oxides (NOₓ) with ammonia (NH₃), but the low-temperature rate dependence on copper (Cu) volumetric density is inconsistent with reaction at single sites. We combine steady-state and transient kinetic measurements, x-ray absorption spectroscopy, and first-principles calculations to demonstrate that under reaction conditions, mobilized Cu ions can travel through zeolite windows and form transient ion pairs that participate in an oxygen (O₂)–mediated CuI→CuII redox step integral to SCR. Electrostatic tethering to framework aluminum centers limits the volume that each ion can explore and thus its capacity to form an ion pair. The dynamic, reversible formation of multinuclear sites from mobilized single atoms represents a distinct phenomenon that falls outside the conventional boundaries of a heterogeneous or homogeneous catalyst.

Electrochemistry has the potential to sustainably transform molecules with electrons supplied by renewable electricity. It is one of many solutions towards a more circular, sustainable and equitable society. To achieve this, collaboration between industry and research laboratories is a must. Atomistic understanding from fundamental experiments and modelling can be used to engineer optimized systems whereas limitations set by the scaled-up technology can direct the systems studied in the research laboratory. In this Primer, best practices to run clean laboratory-scale electrochemical systems and tips for the analysis of electrochemical data to improve accuracy and reproducibility are introduced. How characterization and modelling are indispensable in providing routes to garner further insights into atomistic and mechanistic details is discussed. Finally, important considerations regarding material and cell design for scaling up water electrolysis are highlighted and the role of hydrogen in our society’s energy transition is discussed. The future of electrochemistry is bright and major breakthroughs will come with rigour and improvements in the collection, analysis, benchmarking and reporting of electrochemical water splitting data.Electrochemical water splitting using renewable electricity is a promising method for the sustainable production of hydrogen. This Primer overviews considerations, techniques and methods for water electrolysis and describes methods to improve rigour and reproducibility when analysing electrochemical data.

Selective catalytic reduction of NO x with hydrogen (H 2 -SCR) in excess oxygen over Pd and Ir based catalysts with various silica supports was studied. The Pd/V 2 O 5 /TiO 2 /SBA-15 and Ir/SBA-15 catalysts showed the highest activities. The effects of noble metal, various silica supports, CO and SO 2 on H 2 -SCR over these catalysts were also studied and compared, and possible underlying mechanisms discussed. A comparison of 1 % Ir-doped on silicas with a wide range of pore sizes showed that the peak temperature (where the NO conversion maximum was located) was directly related to the pore size: larger pores of the support resulted in higher peak temperatures. This result indicates that pore diffusion limitation played a role in determining the peak temperature. In addition, a non-noble metal catalyst, Nb 2 O 5 /SiO 2 , was found to have considerable activity. Graphical Abstract Larger pores of the support resulted in higher peak temperatures, which indicated that pore diffusion limitation played a direct role.

Copper ions in zeolites help remove noxious nitrogen oxides from diesel exhaust by catalyzing their reaction with ammonia and oxygen. Paolucci et al. found that these copper ions may move about during the reaction (see the Perspective by Janssens and Vennestrom). Zeolite catalysts generally fix metals in place while the reacting partners flow in and out of their cagelike structures. In this case, though, x-ray absorption spectroscopy suggested that the ammonia was mobilizing the copper ions to pair up as they activated oxygen during the catalytic cycle. Science , this issue p. 898 ; see also p. 866 Copper ions can move about and pair up in a zeolite framework as they catalyze nitric oxide removal from diesel exhaust. Copper ions exchanged into zeolites are active for the selective catalytic reduction (SCR) of nitrogen oxides (NO x ) with ammonia (NH 3 ), but the low-temperature rate dependence on copper (Cu) volumetric density is inconsistent with reaction at single sites. We combine steady-state and transient kinetic measurements, x-ray absorption spectroscopy, and first-principles calculations to demonstrate that under reaction conditions, mobilized Cu ions can travel through zeolite windows and form transient ion pairs that participate in an oxygen (O 2 )–mediated Cu I →Cu II redox step integral to SCR. Electrostatic tethering to framework aluminum centers limits the volume that each ion can explore and thus its capacity to form an ion pair. The dynamic, reversible formation of multinuclear sites from mobilized single atoms represents a distinct phenomenon that falls outside the conventional boundaries of a heterogeneous or homogeneous catalyst.

The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection. Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and antiviral discovery are hampered by the lack of a cell-based virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a noninfectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny virions. Its replication can be inhibited by RdRp mutations or by known SARS-CoV-2 antiviral compounds. Using this system, a high-throughput antiviral assay has also been developed. Significant differences in potencies of several SARS-CoV-2 inhibitors in different cell lines were observed, which highlight the challenges of discovering antivirals capable of inhibiting viral replication in vivo and the importance of testing compounds in multiple cell culture models. The generation of a SARS-CoV-2 replicon provides a powerful platform to expand the global research effort to combat COVID-19.

Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of ‘newly born’ cells would be highest in the LNs. Using a deuterium oxide ( 2 H) in vivo labeling method in which patients consumed deuterated (heavy) water ( 2 H 2 O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4 dim CD5 bright phenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.

Background Understanding carboplatin resistance in ovarian cancer is critical for the improvement of patients’ lives. Multipotent mesenchymal stem cells or an aggravated epithelial to mesenchymal transition phenotype of a cancer are integrally involved in pathways conferring chemo-resistance. Long non-coding RNA HOTAIR (HOX transcript antisense intergenic RNA) is involved in mesenchymal stem cell fate and cancer biology. Methods We analyzed HOTAIR expression and associated surrogate DNA methylation (DNAme) in 134 primary ovarian cancer cases (63 received carboplatin, 55 received cisplatin and 16 no chemotherapy). We validated our findings by HOTAIR expression and DNAme analysis in a multicentre setting of five additional sets, encompassing 946 ovarian cancers. Chemo-sensitivity has been assessed in cell culture experiments. Results HOTAIR expression was significantly associated with poor survival in carboplatin-treated patients with adjusted hazard ratios for death of 3.64 (95 % confidence interval [CI] 1.78–7.42; P  < 0.001) in the discovery and 1.63 (95 % CI 1.04–2.56; P  = 0.032) in the validation set. This effect was not seen in patients who did not receive carboplatin (0.97 [95 % CI 0.52–1.80; P  = 0.932]). HOTAIR expression or its surrogate DNAme signature predicted poor outcome in all additional sets of carboplatin-treated ovarian cancer patients while HOTAIR expressors responded preferentially to cisplatin (multivariate interaction P  = 0.008). Conclusions Non-coding RNA HOTAIR or its more stable DNAme surrogate may indicate the presence of a subset of cells which confer resistance to carboplatin and can serve as (1) a marker to personalise treatment and (2) a novel target to overcome carboplatin resistance.