Low-nuclearity CuZn ensembles on ZnZrOx catalyze methanol synthesis from CO2.

Metal promotion could unlock high performance in zinc-zirconium catalysts, ZnZrOx, for CO2 hydrogenation to methanol. Still, with most efforts devoted to costly palladium, the optimal metal choice and necessary atomic-level architecture remain unclear. Herein, we investigate the promotion of ZnZrOx catalysts with small amounts (0.5 mol%) of diverse hydrogenation metals (Re, Co, Au, Ni, Rh, Ag, Ir, Ru, Pt, Pd, and Cu) prepared via a standardized flame spray pyrolysis approach. Cu emerges as the most effective promoter, doubling methanol productivity. Operando X-ray absorption, infrared, and electron paramagnetic resonance spectroscopic analyses and density functional theory simulations reveal that Cu0 species form Zn-rich low-nuclearity CuZn clusters on the ZrO2 surface during reaction, which correlates with the generation of oxygen vacancies in their vicinity. Mechanistic studies demonstrate that this catalytic ensemble promotes the rapid hydrogenation of intermediate formate into methanol while effectively suppressing CO production, showcasing the potential of low-nuclearity metal ensembles in CO2-based methanol synthesis.

The Future of Chemical Sciences is Sustainable.

Chemistry, a vital tool for sustainable development, faces a challenge due to the lack of clear guidance on actionable steps, hindering the optimal adoption of sustainability practices across its diverse facets from discovery to implementation. This Scientific Perspective explores established frameworks and principles, proposing a conciliated set of triple E priorities anchored on Environmental, Economic, and Equity pillars for research and decision making. We outline associated metrics, crucial for quantifying impacts, classifying them according to their focus areas and scales tackled. Emphasizing catalysis as a key driver of sustainable synthesis of chemicals and materials, we exemplify how triple E priorities can practically guide the development and implementation of processes from renewables conversions to complex customized products. We summarize by proposing a roadmap for the community aimed at raising awareness, fostering academia-industry collaboration, and stimulating further advances in sustainable chemical technologies across their broad scope.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimen to prevent antagonistic effects. Thus, this work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

CO Cofeeding Affects Product Distribution in CH3Cl Coupling over ZSM-5 Zeolite: Pressure Twists the Plot.

C1 coupling reactions over zeolite catalysts are central to sustainable chemical production strategies. However, questions persist regarding the involvement of CO in ketene formation, and the impact of this elusive oxygenate intermediate on reactivity patterns. Using operando photoelectron photoion coincidence spectroscopy (PEPICO), we investigate the role of CO in methyl chloride conversion to hydrocarbons (MCTH), a prospective process for methane valorization with a reaction network akin to methanol to hydrocarbons (MTH) but without oxygenate intermediates. Our findings reveal the transformative role of CO in MCTH at the low pressures, inducing ketene formation in MCTH and boosting olefin production, confirming the Koch carbonylation step in the initial stages of C1 coupling. We uncover pressure-dependent product distributions driven by CO-induced ketene formation, and its subsequent desorption from the zeolite surface, which is enhanced at low pressure. Inspired by the above results, extension of the co-feeding approach to CH3OH as another simple oxygenate showcases the additional potential for improved catalyst stability in MCTH at ambient pressure.

Machine learning in small sample neuroimaging studies: Novel measures for schizophrenia analysis.

Novel features derived from imaging and artificial intelligence systems are commonly coupled to construct computer-aided diagnosis (CAD) systems that are intended as clinical support tools or for investigation of complex biological patterns. This study used sulcal patterns from structural images of the brain as the basis for classifying patients with schizophrenia from unaffected controls. Statistical, machine learning and deep learning techniques were sequentially applied as a demonstration of how a CAD system might be comprehensively evaluated in the absence of prior empirical work or extant literature to guide development, and the availability of only small sample datasets. Sulcal features of the entire cerebral cortex were derived from 58 schizophrenia patients and 56 healthy controls. No similar CAD systems has been reported that uses sulcal features from the entire cortex. We considered all the stages in a CAD system workflow: preprocessing, feature selection and extraction, and classification. The explainable AI techniques Local Interpretable Model-agnostic Explanations and SHapley Additive exPlanations were applied to detect the relevance of features to classification. At each stage, alternatives were compared in terms of their performance in the context of a small sample. Differentiating sulcal patterns were located in temporal and precentral areas, as well as the collateral fissure. We also verified the benefits of applying dimensionality reduction techniques and validation methods, such as resubstitution with upper bound correction, to optimize performance.

Droplet-Based Microfluidics Reveals Insights into Cross-Coupling Mechanisms over Single-Atom Heterogeneous Catalysts.

Single-atom heterogeneous catalysts (SACs) hold promise as sustainable alternatives to metal complexes in organic transformations. However, their working structure and dynamics remain poorly understood, hindering advances in their design. Exploiting the unique features of droplet-based microfluidics, we present the first in-situ assessment of a palladium SAC based on exfoliated carbon nitride in Suzuki-Miyaura cross-coupling using X-ray absorption spectroscopy. Our results confirm a surface-catalyzed mechanism, revealing the distinct electronic structure of active Pd centers compared to homogeneous systems, and providing insights into the stabilizing role of ligands and bases. This study establishes a valuable framework for advancing mechanistic understanding of organic syntheses catalyzed by SACs.

Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens.

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren's syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.

LncRNA MALAT1 in Keratinocyte function: A review of recent advances.

Keratinocytes, the principal epidermal cells, play a vital role in maintaining the structural integrity and functionality of the skin. Beyond their protective role, keratinocytes are key contributors to the process of wound healing, as they migrate to injury sites, proliferate, and generate new layers of epidermis, facilitating tissue repair and remodeling. Moreover, keratinocytes actively participate in the skin's immune responses, expressing pattern recognition receptors (PRRs) to detect microbial components and interact with immune cells to influence adaptive immunity. Keratinocytes express a diverse repertoire of signaling pathways, transcription factors, and epigenetic regulators to regulate their growth, differentiation, and response to environmental cues. Among these regulatory elements, long non-coding RNAs (lncRNAs) have emerged as essential players in keratinocyte biology. LncRNAs, including MALAT1, play diverse roles in gene regulation and cellular processes, influencing keratinocyte proliferation, differentiation, migration, and response to environmental stimuli. Dysregulation of specific lncRNAs such as MALAT1 can disrupt keratinocyte homeostasis, leading to impaired differentiation, compromised barrier integrity, and contributing to the pathogenesis of various skin disorders. Understanding the intricate interplay between lncRNAs and keratinocytes offers promising insights into the molecular underpinnings of skin health and disease, with potential implications for targeted therapies and advancements in dermatological research. Hence, our objective is to provide a comprehensive summary of the available knowledge concerning keratinocytes and their intricate relationship with MALAT1.

Active Learning-Based Guided Synthesis of Engineered Biochar for CO2 Capture.

Biomass waste-derived engineered biochar for CO2 capture presents a viable route for climate change mitigation and sustainable waste management. However, optimally synthesizing them for enhanced performance is time- and labor-intensive. To address these issues, we devise an active learning strategy to guide and expedite their synthesis with improved CO2 adsorption capacities. Our framework learns from experimental data and recommends optimal synthesis parameters, aiming to maximize the narrow micropore volume of engineered biochar, which exhibits a linear correlation with its CO2 adsorption capacity. We experimentally validate the active learning predictions, and these data are iteratively leveraged for subsequent model training and revalidation, thereby establishing a closed loop. Over three active learning cycles, we synthesized 16 property-specific engineered biochar samples such that the CO2 uptake nearly doubled by the final round. We demonstrate a data-driven workflow to accelerate the development of high-performance engineered biochar with enhanced CO2 uptake and broader applications as a functional material.

CO2 Electroreduction To Syngas With Tunable Composition In An Artificial Leaf.

Invited for this month's cover is the group of Javier Pérez-Ramírez at ETH Zürich, which collaborated with the group of Tsvetelina Merdzhanova at Forschungszentrum Jülich. The image shows how artificial leaves, able to recycle carbon dioxide into syngas of variable composition, could be integrated with chemical plants. The Research Article itself is available at 10.1002/cssc.202301398.

CO2 Electroreduction To Syngas With Tunable Composition In An Artificial Leaf.

Artificial leaves (a-leaves) can reduce carbon dioxide into syngas using solar power and could be combined with thermo- and biocatalytic technologies to decentralize the production of valuable products. By providing variable CO : H2 ratios on demand, a-leaves could facilitate optimal combinations and control the distribution of products in most of these hybrid systems. However, the current design procedures of a-leaves concentrate on achieving high performance for a predetermined syngas composition. This study demonstrates that incorporating the electrolyte flow as a design variable enables flexible production without compromising performance. The concept was tested on an a-leaf using a commercial cell, a Cu2 O:Inx cathodic catalyst, and an inexpensive amorphous silicon thin-film photovoltaic module. Syngas with CO : H2 ratio in the range of 1.8-2.3 could be attained with only 2 % deviation from the optimal cell voltage and controllable solely by catholyte flow. These features could be beneficial for downstream technologies such as Fischer-Tropsch synthesis and anaerobic fermentation.

Quantitative Description of Metal Center Organization and Interactions in Single-Atom Catalysts.

Ultra-high-density single-atom catalysts (UHD-SACs) present unique opportunities for harnessing cooperative effects between neighboring metal centers. However, the lack of tools to establish correlations between the density, types, and arrangements of isolated metal atoms and the support surface properties hinders efforts to engineer advanced material architectures. Here, this work precisely describes the metal center organization in various mono- and multimetallic UHD-SACs based on nitrogen-doped carbon (NC) supports by coupling transmission electron microscopy with tailored machine-learning methods (released as a user-friendly web app) and density functional theory simulations. This approach quantifies the non-negligible presence of multimers with increasing atom density, characterizes the size and shape of these low-nuclearity clusters, and identifies surface atom density criteria to ensure isolation. Further, it provides previously inaccessible experimental insights into coordination site arrangements in the NC host, uncovering a repulsive interaction that influences the disordered distribution of metal centers in UHD-SACs. This observation holds in multimetallic systems, where chemically-specific analysis quantifies the degree of intermixing. These fundamental insights into the materials chemistry of single-atom catalysts are crucial for designing catalytic systems with superior reactivity.

Consumer Grade Polyethylene Recycling via Hydrogenolysis on Ultrafine Supported Ruthenium Nanoparticles.

Catalytic hydrogenolysis has the potential to convert high-density polyethylene (HDPE), which comprises about 30 % of plastic waste, into valuable alkanes. Most investigations have focused on increasing activity for lab grade HDPEs displaying low molecular weight, with limited mechanistic understanding of the product distribution. No efficient catalyst is available for consumer grades due to their lower reactivity. This study targets HDPE used in bottle caps, a waste form generated globally at a rate of approximately one million units per hour. Ultrafine ruthenium particles (1 nm) supported on titania (anatase) achieved up to 80 % conversion into light alkanes (C1 -C45 ) under mild conditions (498 K, 20 bar H2 , 4 h) and were reused for three cycles. Small ruthenium nanoparticles were critical to achieving relevant conversions, as activity sharply decreased with particle size. Selectivity commonalities and peculiarities across HDPE grades were disclosed by a reaction modelling approach applied to products. Isomerization cedes to backbone scission as the reaction progresses. Within this trend, low molecular weight favor isomerization whilst high molecular weight favor cleavage. Commercial caps obeyed this trend with decreased activity, anticipating the influence of additives in realistic processing. This study demonstrates effective hydrogenolysis of consumer grade polyethylene and provides selectivity patterns for product control.

Aiming for More Sustainable Cross-Coupling Chemistry by Employing Single-Atom Catalysis on Scale.

Scaling up syntheses from mg to kg quantities is a complex endeavor. Besides adapting laboratory protocols to industrial processes and equipment and thorough safety assessments, much attention is paid to the reduction of the process' environmental impact. For processes including transition metal catalyzed steps, e.g. cross-coupling chemistry, this impact strongly depends on the identity of the metal used. As such, a key approach is the replacement of single-use with reusable heterogeneous catalysts. Transition metal single-atom heterogeneous catalysts (SAC), a novel class of catalytic materials, might exhibit all the necessary properties to step up to this task. This article shall discuss current applications of SAC in cross-coupling chemistry from the point of a process chemist and shed light on the NCCR Catalysis contribution to the field. Investigations of the stability-activity-selectivity relationship of SACs in combination with early-stage life-cycle assessments (LCA) of potential processes lay the foundation for large-scale application tailored catalyst synthesis. Ultimately, prevailing challenges are highlighted, which need to be addressed in future research.

Operando Photoelectron Photoion Coincidence Spectroscopy to Detect Short-lived Intermediates in Catalysis.

Understanding the reaction mechanism is critical yet challenging in heterogeneous catalysis. Reactive intermediates, e.g., radicals and ketenes, are short-lived and often evade detection. In this review, we summarize recent developments with operando photoelectron photoion coincidence (PEPICO) spectroscopy as a versatile tool capable of detecting elusive intermediates. PEPICO combines the advantages of mass spectrometry and the isomer-selectivity of threshold photoelectron spectroscopy. Recent applications of PEPICO in understanding catalyst synthesis and catalytic reaction mechanisms involving gaseous and surface-confined radical and ketene chemistry will be summarized.

The Environmental Feasibility of Decentralised Solar Ammonia.

Intense efforts have been devoted to developing green and blue centralised Haber-Bosch processes (gHB and bHB, respectively), but the feasibility of a decentralised and sustainable scheme has yet to be assessed. Here we reveal the conditions under which small-scale systems based on the electrocatalytic reduction of nitrogen (eN2R) powered by photovoltaic energy (NH3-leaf) could become a competitive technology in terms of environmental criteria. To this end, we calculated energy efficiency targets based on solar irradiation atlases to guide research in the incipient eN2R field. Even under this germinal state, the NH3-leaf technology would compete favourably in sunny locations relative to the business-as-usual production scenario. The disclosed sustainability potential of NH3-leaf makes it a strong ally of gHB toward a non-fossil ammonia production.

Language models and protocol standardization guidelines for accelerating synthesis planning in heterogeneous catalysis.

Synthesis protocol exploration is paramount in catalyst discovery, yet keeping pace with rapid literature advances is increasingly time intensive. Automated synthesis protocol analysis is attractive for swiftly identifying opportunities and informing predictive models, however such applications in heterogeneous catalysis remain limited. In this proof-of-concept, we introduce a transformer model for this task, exemplified using single-atom heterogeneous catalysts (SACs), a rapidly expanding catalyst family. Our model adeptly converts SAC protocols into action sequences, and we use this output to facilitate statistical inference of their synthesis trends and applications, potentially expediting literature review and analysis. We demonstrate the model's adaptability across distinct heterogeneous catalyst families, underscoring its versatility. Finally, our study highlights a critical issue: the lack of standardization in reporting protocols hampers machine-reading capabilities. Embracing digital advances in catalysis demands a shift in data reporting norms, and to this end, we offer guidelines for writing protocols, significantly improving machine-readability. We release our model as an open-source web application, inviting a fresh approach to accelerate heterogeneous catalysis synthesis planning.

Mechanistic modeling for optimal design of dissolvable microneedle-based patches for transdermal drug delivery.

Polymeric microneedle (MN)-based patches are an efficient, non-invasive, and painless means of drug delivery through the skin to systemic circulation. The design of these MN-based patches can be customized for various drug delivery applications, particularly modified release of drugs. In this study, we developed a mathematical model of drug delivery via MN-based patches to study the effect of patch design properties on drug delivery kinetics and systemic pharmacokinetics (PK). We calibrated the model against two representative formulations: a rapid release patch of naloxone and a sustained-release patch of levonorgestrel. The model was then applied to assess the relative significance of model parameters in governing systemic PK of drugs and obtain optimal design parameters to achieve therapeutically meaningful drug levels in a clinical setting. We identified the importance of drug loading fraction, MN base radius, and MN height as the key control parameters responsible for drug PK.Clinical Relevance- Through the application of modeling and simulation, we can improve drug delivery from MN-based patches by identifying optimal design parameters to support the clinical translation of these novel drug delivery systems.