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The molecular functions of a protein are defined by its inherent properties in relation to its environment and interaction network. Within a cell, this environment and network are defined by the subcellular location of the protein. Consequently, it is crucial to know the localization of a protein to fully understand its functions. Recently, we have developed a mass spectrometry- (MS) and bioinformatics-based pipeline to generate a proteome-wide resource for protein subcellular localization across multiple human cancer cell lines ( www.subcellbarcode.org ). Here, we present a detailed wet-lab protocol spanning from subcellular fractionation to MS-sample preparation and analysis. A key feature of this protocol is that it includes all generated cell fractions without discarding any material during the fractionation process. We also describe the subsequent quantitative MS-data analysis, machine learning-based classification, differential localization analysis and visualization of the output. For broad applicability, we evaluated the pipeline by using MS data generated by two different peptide pre-fractionation approaches, namely high-resolution isoelectric focusing and high-pH reverse-phase fractionation, as well as direct analysis without pre-fractionation by using long-gradient liquid chromatography-MS. Moreover, an R package covering the dry-lab part of the method was developed and made available through Bioconductor. The method is straightforward and robust, and the entire protocol, from cell harvest to classification output, can be performed within 1-2 weeks. The protocol enables accurate classification of proteins to 15 compartments and 4 neighborhoods, visualization of the output data and differential localization analysis including treatment-induced protein relocalization, condition-dependent localization or cell type-specific localization. The SubCellBarCode package is freely available at https://bioconductor.org/packages/devel/bioc/html/SubCellBarCode.html .

We investigated the influence of signal transducer and activator of transcription-3 (STAT3) on the spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we hoped to identify whether transfection of the STAT3 overexpression plasmid increases the survival of spinal cord transplantation in order to improve therapeutic efficacy. The fetal rat model of spina bifida aperta was established using retinoic acid and treated with a microsurgical injection of bone marrow mesenchymal stem cells (BMSCs). The animals were divided into either the blank control group, negative control group or the experimental group. The optical density (OD) value of BMSCs viability was determined using the Cell Counting Kit-8 (CCK-8). The expression of STAT3, phosphorylated STAT3 (pSTAT3), neural markers and apoptosis-related factors were evaluated using real-time PCR and Western blot. The OD value in the experimental group was highest at eight hours after transplantation using CCK-8. The expression of pSTAT3, glial fibrillary acidic protein, neuron-specific enolase, neurofilament and nestin in the experimental group was significantly higher compared to the blank control group and negative control group (P

It remains a research challenge in determining the catalytic reaction mechanisms primarily caused by the difficulty to experimentally identify active intermediates with current analytic characterizations. Although computational chemistry has provided an alternative approach to simulate the catalysis process and achieve insights into the reaction pathways, the simulation results would not be conclusive without experimental evidence. Herein, we investigate spatiotemporal electrostatic potential (ESP) distribution surrounding reacting molecules during the catalysis process and suggest its use as a fingerprint to help differentiate and identify active intermediates. Our ESP study of ammonia synthesis on the Ru surface shows a high spatial sensitivity of ESP distribution to molecular configuration and structure of intermediate species and only minor temporal ESP oscillation throughout the lifetime of the intermediates, which provides strong theoretical support to use ESP distribution as a new approach to characterize intermediates. With the ESP measurements at the microscale and in real-time, turning feasible, experimental identification of active intermediates and determination of reaction pathways would become possible by measuring the ESP surrounding the reacting molecules. We suggest developing ESP measurement tools to experimentally explore and unveil reaction mechanisms.

CO2 hydrogenation into valuable chemical products has attracted intensive research interest in recent years, with product selectivity control remaining an important topic that requires fine tuning of the catalytic structure and mechanistic understanding. Herein we report our study of anionic phosphorus-regulated indium oxide In2O3 (P-In2O3) nanocatalyst materials for CO2 hydrogenation and achieve nearly full-range selectivity control between methanol and CO products by means of tuning the P content. In situ DRIFTS experiments and XPS characterization reveal the importance of P anion regulation in controlling the CO2 hydrogenation pathways, with an increase in the P content resulting in a decrease in the reducibility of In2O3 that alters CO2 adsorption configuration by blocking and weakening oxygen vacancy (OV) sites for methanol generation and in the meantime creates new sites predominantly active for CO generation. This study demonstrates excellent control of the product selectivity property by regulating the catalyst composition with P anions and provides mechanistic discussions, which offers a new, effective strategy in CO2 hydrogenation catalyst research.

Mesoporous carbon (MPC) nanomaterials, with large specific surface area, excellent conductivity and stability, and effective mass transfer are beneficial for use as catalyst support in electrochemical oxygen reduction reaction (ORR) for fuel cell applications. However, MPC utilization was limited by difficulties in loading catalyst nanoparticles within the MPC pores while simultaneously controlling critical particle parameters such as size and distribution. In this study we report a new vacuum impregnation method combined with solid-state chemistry synthesis for preparing highly active ORR catalyst nanoparticles on MPC supports. We confirm the effectiveness of this method by synthesizing octahedral Pt2CuNi nanoparticles on hydrophilic MPC with an even particle distribution in the MPC pores. We also demonstrate the capability of this method in controlling the particle size and morphology by adjusting the synthesis parameters. The synthesized catalysts exhibited excellent ORR activity and promising durability, which proves the goodness of using MPC support in ORR electrocatalysis. The findings offer a new methodology for synthesizing nanoparticles in MPC pores with parameter control and provide an intriguing strategy to develop new ORR catalysts using MPC support structure.

Formaldehyde is an essential building block for hundreds of chemicals and a promising liquid organic hydrogen carrier (LOHC), yet its indirect energy-intensive synthesis process prohibits it from playing a more significant role. Here we report a direct CO reduction to formaldehyde (CORTF) process that utilizes hydrogen underpotential deposition to overcome the thermodynamic barrier and the scaling relationship restriction. This is the first time that this reaction has been realized under ambient conditions. Using molybdenum phosphide as a catalyst, formaldehyde was produced with nearly a 100% faradaic efficiency in aqueous KOH solution, with its formation rate being one order of magnitude higher compared with the state-of-the-art thermal catalysis approach. Simultaneous tuning of the current density and reaction temperature led to a more selective and productive formaldehyde synthesis, indicating the electrochemical and thermal duality of this reaction. DFT calculations revealed that the desorption of the *H2CO intermediate likely served as the rate-limiting step, and the participation of H2O made the reaction thermodynamically favorable. Furthermore, a full-cell reaction set-up was demonstrated with CO hydrogenation to HCHO achieved without any energy input, which fully realized the spontaneous potential of the reaction. Our study shows the feasibility of combining thermal and electrochemical approaches for realizing the thermodynamics and for scaling relationship-confined reactions, which could serve as a new strategy in future reaction design.

The associated publication reports proteogenomic analysis of non-small cell lung cancer, where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes histological, tertiary lymphoid structure (TLS), and immunohistochemical evaluation of clinical samples. Specifically, immunohistochemistry was performed for PD-L1, CD3, and CD8 on tumor microarrays (TMAs) derived from formalin-fixed paraffin embedded (FFPE) samples.

The associated publication reports proteogenomic analysis of non-small cell lung cancer (NSCLC), where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes sections of the bioinformatics analysis of the multi-omics data, namely, data analysis and processing for panel sequencing, identification of cancer- and driver-related proteins in proteomics data, proteogenomics search, and machine learning-based classifiers for NSCLC subtyping. Specifically, a cohort classifier was built using support-vector machine-recursive feature elimination (SVM-RFE) algorithm applied to in-depth proteomics data from a cohort of 141 samples. The classifier was then validated in three external datasets. Another classifier, suitable for single-sample subtyping, was built using k-top scoring pairs (k-TSP) algorithm applied to label-free data from a cohort of 136 samples. The k-TSP-based classifier was validated in two independent cohorts and an additional external dataset.

The associated publication reports proteogenomic analysis of non-small cell lung cancer (NSCLC), where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. The in-depth proteomic analysis pointed to a potential role of STK11 inactivation in liver-specific signaling and subsequent cancer growth and immune evasion mechanisms. This protocol describes in vitro validation of the downstream effects of STK11-AMPK signaling on HNF1A and FGL1 in a liver and two lung cancer cell lines.

The associated publication reports proteogenomic analysis of non-small cell lung cancer, where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes the sample preparation and mass spectrometry (MS)-based in-depth and rapid proteomic analyses of tumor and biopsy samples. We deployed single-pot solid-phase-enhanced sample preparation (SP3). For the in-depth analysis, we used TMT labeling, followed by high-resolution isoelectric focusing (HiRIEF) prefractionation and LC-MS with data-dependent acquisition (DDA). The reported protocol achieved analytical depth of close to 14,000 quantified proteins and almost 10,000 across the entire cohort of 141 samples. The rapid analysis was label-free, based on LC-MS with data-independent acquisition (DIA). The median number of identified proteins was 3,967 and 3,552 in two independent cohorts of tumor samples (n = 141 and 208, respectively), and 2,494 in another cohort of biopsy material (n = 84).

Proximity to graphene has an extraordinary effect on the dynamics of entangled chains, as evidenced by strong slowing of thermally stimulated fluctuations at the surface of a thin supported film of polystyrene (PS) when a single layer of graphene is placed between the supporting substrate and the PS film. This slowing is due to a layer of highly viscous polymer next to the substrate being thicker for graphene (75 nm or 7.5Rg) than for silicon (13 nm or 1.3Rg). Molecular dynamics simulations of unentangled PS chain melts on silicon and on multiple layers of graphene show that the work of adhesion with graphene is roughly 4 times larger than that with silicon. In addition, PS chains adjacent to silicon readily form loops, with phenyl rings pointing predominantly toward the substrate. Chains adjacent to graphene more readily form trains, with the phenyl rings predominantly parallel to the graphene.

Designing highly active oxygen reduction reaction (ORR) catalysts is crucial to boost the fuel cell economy. Previous research has mainly focused on Pt-based alloy catalysts in which surface Pt is the solely active site and the activity improvement was challenged by the discovered scaling relationship. Herein we report a new concept of utilizing dual active sites for the ORR and demonstrate its effectiveness by synthesizing a SnO x/Pt-Cu-Ni heterojunctioned catalyst. A maximum of 40% enhancement in the apparent specific activity, which corresponds to 10-fold enhancement on interface sites, is measured compared with pure Pt-Cu-Ni. Detailed investigations suggest an altered dual-site cascade mechanism wherein the first two steps occur on SnO x sites and the remaining steps occur on adjacent Pt sites, allowing a significant decrease in the energy barrier. This study with the suggested dual-site cascade mechanism shows the potential to overcome the ORR energy barrier bottleneck to develop highly active catalysts.

Methanol synthesis via CO2 hydrogenation has attracted intensive research efforts, but is challenged with development of active and selective catalyst materials that would allow the reaction occurs under milder conditions and being economically more viable. Herein we report the use of bifunctional active sites and their synergy in promoting CO2 hydrogenation kinetics and selectivity. A series of Cu-In-Zr-O mixed oxide nanomaterials containing Cu and defective In2O3 active sites were synthesized and studied for the catalytic properties. Significantly higher CO2 conversion and methanol selectivity were achieved using the Cu-In-Zr-O compared to its non-copper counterpart In-Zr-O, revealing synergy between the two active sites. Insights into the mechanism and functionality of the two actives in CO2 hydrogenation catalysis were obtained with in situ DRIFTS study. A formate-methoxy-methanol pathway and the possible rate-limiting steps were discovered. The excellent selectivity property of the Cu-In-Zr-O was attributed to strong adsorption of CO2 to defective In2O3, which creates a large energy barrier that suppresses CO2 dissociation into CO. The promotion in CO2 hydrogenation kinetics was attributed to cooperation between the bifunctional active sites, with Cu sites adsorb and provide active hydrogen atoms that hydrogenate adsorbed CO2 at adjacent defective In2O3 sites. The findings confirmed synergy between bifunctional sites in CO2 hydrogenation catalysis and provided a new concept in development of active and selective catalyst materials.

The eukaryotic cell is compartmentalized into subcellular niches, including membrane-bound and membrane-less organelles. Proteins localize to these niches to fulfil their function, enabling discreet biological processes to occur in synchrony. Dynamic movement of proteins between niches is essential for cellular processes such as signalling, growth, proliferation, motility and programmed cell death, and mutations causing aberrant protein localization are associated with a wide range of diseases. Determining the location of proteins in different cell states and cell types and how proteins relocalize following perturbation is important for understanding their functions, related cellular processes and pathologies associated with their mislocalization. In this Primer, we cover the major spatial proteomics methods for determining the location, distribution and abundance of proteins within subcellular structures. These technologies include fluorescent imaging, protein proximity labelling, organelle purification and cell-wide biochemical fractionation. We describe their workflows, data outputs and applications in exploring different cell biological scenarios, and discuss their main limitations. Finally, we describe emerging technologies and identify areas that require technological innovation to allow better characterization of the spatial proteome.

Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples. Lehtio and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.

Fine-tuning strain and vacancies in 2H-phase transition-metal dichalcogenides, although extremely challenging, is crucial for activating the inert basal plane for boosting the hydrogen evolution reaction (HER). Here, atomically curved 2H-WS2 nanosheets with precisely tunable strain and sulfur vacancies (S-vacancies) along with rich edge sites are synthesized via a one-step approach by harnessing geometric constraints. The approach is based on the confined epitaxy growth of WS2 in ordered mesoporous graphene derived from nanocrystal superlattices. The spherical curvature imposed by the graphitic mesopores enables the generation of uniform strain and S-vacancies in the as-grown WS2 nanosheets, and simultaneous manipulation of these two key parameters can be realized by simply adjusting the pore size. In addition, the formation of unique mesoporous WS2 @graphene van der Waals heterostructures ensures the ready access of active sites. Fine-tuning the WS2 layer number, strain, and S-vacancies enables arguably the best-performing HER 2H-WS2 electrocatalysts ever reported. Density functional theory calculations indicate that compared with strain, S-vacancies play a more critical role in enhancing the HER activity.

Capacitive deionization (CDI) is an energy saving and environmentally friendly technology for water desalination. However, classical CDI is challenged by a low salt removal capacity. To improve the desalination capacity, electrode materials utilizing the battery mechanism for salt ion removal have emerged as a new direction more recently. In this work, we report a study of amorphous iron phosphate (FePO4) as a promising electrode material for pseudocapacitive sodium ion removal. Sodium ions can be effectively, reversibly intercalated and de-intercalated upon its electrochemical reduction and oxidation, with an excellent sodium ion capacity under half-cell testing conditions. By assembling a hybrid CDI (HCDI) system utilizing the FePO4 electrode for pseudocapacitive sodium ion removal and active carbon electrode for capacitive chloride ion removal, the cell exhibited a high salt removal capacity and good reversibility and durability, which was attributed to the advantageous features of amorphous FePO4. The HCDI system achieved a high deionization capacity (82 mg g−1) in 10 mM NaCl, a fast deionization rate (0.046 mg g−1 s−1), and good stability and cyclability.

International audience; In this study, a specifically designed B4C–TiB2 composite with the typical microstructural feature of a TiB2 network (cages) that encapsulates a B4C matrix was fabricated by the molten-salt and spark plasma sintering (SPS) method. The finite-element (FE) calculation results show that the connected TiB2 cages constitute a thermally conductive network, which effectively improves the overall thermal conductivity of the composite; these results agree well with the experimental results. Moreover, the Vickers indentation results reveal that the TiB2 network (cages) can effectively impinge/block the propagation of cracks, which increases the composite toughness. The composite was subjected to helium (He) ion irradiation to simulate the situation in which the B4C–TiB2 composites serve as neutron absorption material, and for which case a high quantity of He atoms is produced by the B10 (n, α) Li7 nuclear reaction. According to the transmission electron microscopy (TEM) results, the interfaces between TiB2 and B4C act as effective sinks for He atoms, and are preferential nucleation sites for He bubbles. The theoretical and experimental results show that when the B4C–TiB2 composites serve as neutron absorption pellets in nuclear reactors, they exhibit a better resistance to their disintegration than pure B4C pellets. Consequently, the performance of the control rods of nuclear reactors can be improved.

Carbon monoxide preferential oxidation (PROX) in an H2-rich stream represents one promising H2 purification technology but requires the development of active and selective catalysts to make the technology viable. We conducted density functional theory simulations of CO PROX catalysis on model Pt alloy systems to establish correlations between the catalyst parameters and the catalytic properties, which validated EA,COOR and EA,HOR as descriptors for CO oxidation and H2 oxidation kinetics, ΔEA as a descriptor for CO PROX selectivity, and ed as a catalyst parameter descriptor for the activation energy barriers. We discovered an interesting compromising relationship between the CO PROX activity and selectivity properties. Pt-Ni and Pt-Mn nanoparticle catalysts were selected for synthesis on the basis of the computational data and tested for their properties, which matched well with the DFT calculations and verified the effectiveness of the computational findings. The use of computation-guided methods and the ...

The synthesis of hierarchical lamellar zeolites with a controlled meso-/microporous morphology and acidity is an expanding area of research interest for a wide range of applications. Here, we report a one-step synthesis of a hierarchical meso-/microporous lamellar MFI–Sn/Al zeolite (i.e., containing both Lewis acidic Sn- and Al-sites and a Bronsted acidic Al–O(H)–Si site) and its catalytic application for the conversion of glucose into 5-(ethoxymethyl)furfural (EMF). The MFI–Sn/Al zeolite was prepared with the assistance of a diquaternary ammonium ([C22H45–N+(CH3)2–C6H12–N+(CH3)2–C6H13]Br2−, C22-6-6) template in a composition of 100SiO2/5C22-6-6/18.5Na2O/xAl2O3/ySnO2/2957H2O (x = 0.5, 1, and 2; y = 1 and 2, respectively). The MFI–Sn/Al zeolites innovatively feature dual meso-/microporosity and dual Lewis and Bronsted acidity, which enabled a three-step reaction cascade for EMF synthesis from glucose in ethanol solvent. The reaction proceeded via the isomerization of glucose to fructose over Lewis acidic Sn sites and the dehydration of fructose to 5-hydroxymethylfurfural (HMF) and then the etherification of HMF and ethanol to EMF over the Bronsted acidic Al–O(H)–Si sites. The co-existence of multiple acidities in a single zeolite catalyst enabled one-pot cascade reactions for carbohydrate upgrading. The dual meso-/microporosity in the MFI–Sn/Al zeolites facilitated mass transport in processing of bulky biomass molecules. The balance of both types of acidity and meso-/microporosity realized an EMF yield as high as 44% from the glucose reactant.

Giant carbon tubes (GCTs) have emerged as a new group of carbon-based material which can exhibit many interesting properties benefiting from the unique physicochemical structure and thus have aroused increasing research interest. Herein, we report a new templated growth approach for the scalable synthesis of amorphous GCTs, which had uniform wall thickness and were ultra-long in length, with the length determined by the template dimension and being demonstrated all the way up to 1 m. The GCTs significantly outperformed other carbon-based sorbents in terms of their oil sorption capacities, oil–water separation capabilities and recyclability properties, and had excellent water oxidation electrocatalysis activity. These interesting properties of the prepared GCTs were discussed to determine the underlying mechanisms and were correlated to their unique structural parameters.

Development of active and durable electrocatalyst for oxygen reduction reaction (ORR) remains one challenge for the polymer electrolyte membrane fuel cell (PEMFC) technology. Pt-based nanomaterials show the greatest promise as electrocatalyst for this reaction among all current catalytic structures. This review focuses on Pt-based ORR catalyst material development and covers the past achievements, current research status and perspectives in this research field. In particular, several important categories of Pt-based catalytic structures and the research advances are summarized. Key factors affecting the catalyst activity and durability are discussed. An outlook of future research direction of ORR catalyst research is provided.

Designing highly active oxygen reduction reaction (ORR) catalysts is crucial to boost the fuel cell economy. Previous research has mainly focused on Pt-based alloy catalysts in which surface Pt is the solely active site and the activity improvement was challenged by the discovered scaling relationship. Herein we report a new concept of utilizing dual active sites for the ORR and demonstrate its effectiveness by synthesizing a SnO

Oxygen evolution reaction (OER) is of great significance for hydrogen production via water electrolysis, which, however, demands development of highly active, durable, and cost-effective electrocatalysts in order to stride into a renewable energy era. Herein, highly efficient and long-term durable OER by coupling B and P into an amorphous porous NiFe-based electrocatalyst is reported, which possesses an amorphous porous metallic bulk structure and high corrosion resistance, and overcomes the issues associated with currently used catalyst nanomaterials. The PB codoping in the activated NiFePB (a-NiFePB) delocalizes both Fe and Ni at Fermi energy level and enhances p-d hybridization as simulated by density functional theory calculations. The harmonized electronic structure and unique porous framework of the a-NiFePB consequently improve the OER activity. The activated NiFePB thus exhibits an extraordinarily low overpotential of 197 mV for harvesting 10 mA cm-2 OER current density and 233 mV for reaching 100 mA cm-2 under chronopotentiometry condition, with the Tafel slope harmoniously conforming to 34 mV dec-1 . Impressive long-term stability of this new catalyst is evidenced by only limited activity decay after 1400 h operation at 100 mA cm-2 . This work strategically directs a way for heading up a promising energy conversion alternative.

Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET. Funding Agencies|NovartisNovartis; Swedish Research CouncilSwedish Research Council; Swedish Cancer SocietySwedish Cancer Society; Cancer Society in Stockholm; Gustav V Jubilee Foundation; Stockholm County CouncilStockholm County Council; Karolinska InstitutetKarolinska Institutet

With clean water availability raising a great technological and social challenge, saltwater desalination has become a key strategic solution. Herein, we report a nickel phthalocyanine tetrasulfonic acid tetrasodium salt (NiPcTATS)-based redox flow desalination cell (RFDC) that allows safe, efficient and continuous water-salt separation. With the new, water-soluble NiPcTATS/NiPcTATS+ redox couple as electrolyte, the RFDC effectively desalinates saltwater and achieves a high average salt removal rate of 3.11 gNaCl/(molNiPcTATS·h) and a low energy consumption of 15.0 kJ/molNaCl at 0.5 V cell voltage. The cell exhibits excellent reversibility and durability for long-term operation, benefiting from the fast-redox kinetics and chemical stability of the redox couple. Efficient solar-driven RFDC for water desalination is demonstrated by powering the cell with a solar panel. This RFDC method provides a low-cost, efficient and safe strategy to purify saltwater, and the findings with NiPcTATS-based redox couple offer new opportunities of utilizing metal phthalocyanines and derivatives in water desalination research.

Formaldehyde is an essential building block for hundreds of chemicals and a promising liquid organic hydrogen carrier (LOHC), yet its indirect energy-intensive synthesis process prohibits it from playing more significant role. Here we report a direct CO reduction to formaldehyde (CORTF) process that hybridizes thermal and electro-catalysis and utilizes hydrogen underpotential deposition property to overcome thermodynamic barrier and scaling relationship restriction. Using molybdenum phosphide as catalyst, formaldehyde can be produced with nearly 100% Faradaic efficiency in aqueous KOH solution, with its formation rate being one order of magnitude higher compared with state-of-the-art thermal catalysis approach. Simultaneous tuning of current density and reaction temperature leads to more selective and productive formaldehyde synthesis, confirming the effectiveness of “hybrid” approach. DFT calculations reveal that desorption of *H2CO intermediate likely serves as rate-limiting step, and the participation of H2O turns the reaction into thermodynamically favorable. Furthermore, a full-cell reaction set-up was demonstrated with CO hydrogenation to HCHO being achieved without any energy input, which shows the spontaneous potential of the reaction. Our study shows the advantage of hybridizing thermal and electro-catalysis in realizing thermodynamics and scaling relation confined reaction, which could serve as a new strategy in future reaction design.

Introduction Oxygen reduction reaction (ORR) accounts for a substantial portion of the energy loss of the proton exchange membrane fuel cell system used for vehicle application. Current state of art ORR catalysts are typically Pt-alloy nanoparticles supported on carbon, of which surface Pt is solely the active site and their activity improvement is fundamentally limited by a “scaling relationship” [1]. In this study, we report the preparation of a SnOx/Pt−Cu−Ni heterojunctioned nanostructure as one potential strategy to break the scaling relationship in ORR. Experimental results confirm a significant activity enhancement compared with pristine Pt−Cu−Ni. Theoretical study suggests a dual-site cascade mechanism wherein the first two steps occur on SnOx sites, followed by transfer of the intermediate to adjacent Pt sites for the subsequent steps. This new catalyst design offers a plausible new approach to achieve high ORR activity on Pt alloys by introducing a second active site. Materials and Methods Pt−Cu−Ni alloy nanoparticles were synthesized by a solid-state chemistry method involving electrochemical treatment to generate a clean Pt surface prior to use in this study [2]. The as prepared Pt-Cu-Ni catalysts were first de-alloyed and then followed by immersion in SnCl2 solution for various time to coat with SnOx [3]. The resulting heterojunctioned catalysts were characterized by HR-TEM, XPS, XANES, as well as in electrochemical measurement to determine the activity and durability. The density functional theory (DFT) simulations were performed with the Quantum ESPRESSO package to calculate the energy states of reaction intermediates on different surface sites. Results and Discussion The conceptual design of the dual site catalyst, as shown in Figure 1(a). involves a possible migration of reaction intermediates during the steps of ORR. Such a migration should be driven by the difference in free energy of the sites. For proof-of-concept, we synthesized Pt−Cu−Ni nanoparticles and then deposited SnOx on the surface to form a heterojunctioned nanostructure (Figure 1(b)). SEM -EDX and XPS analyses confirmed that the SnOx content increased with deposition time, while the Pt:Cu:Ni ratio remained nearly unchanged before and after the deposition. XANES and high resolution XPS characterization suggest the oxidation state of the SnOx is primarily 4+. A decrease of electrochemical active surface area (ECSA) was observed as the deposition time (td) increases (Figure 1 (c)). The mass activity and specific activity (SA) both exhibit a volcano trend with respect to td with the highest values at td=5 min. The apparent SA increased by 40% as compared to the pristine Pt-Cu-Ni, and if only considering the interfacial sites, the estimated specific activity enhancement may be up to 10 folds (Figure 1(d)). While these results provide unambiguous experimental evidence of SnOx’s promoting effect, DFT simulation of the reaction pathways was performed to obtain insight into the possible mechanism (Figure 1(e)). The results suggest the SnOx and the neighboring Pt sites may have cooperated to find the most kinetically favored pathway (Figure 1(f)), wherein the O2 first protonated on SnOx sites to form *OOH and *O intermediates, and then the *O transfers to Pt sites to complete the remaining steps. Conclusion This study demonstrates a strategy to bypass the energy barrier bottleneck of ORR, providing one more dimension of design flexibility towards developing highly active electrode catalysts for fuel cell applications. References Kulkarni, A. et al., Chem. Rev. 2018, 118 (5), 2302−2312. Zhang, C. et al., J. Am. Chem. Soc. 2014, 136 (22), 7805−7808. Shen, X. et al., J. Am. Chem. Soc. 2019, 141(24), 9463-9467. Figure 1

A reliable clean water supply is now one important and challenging issue for the human society. With the facts that only 0.4% of the water on earth is readily drinkable and 98% of the water is saltwater, water desalination for clean water production has become a key strategic solution to satisfy the increasing global water demand. Over the years, different saltwater desalination technologies were researched and developed, including reverse osmosis membrane desalination (RO), electrodialysis (ED), capacitive desalination (CDI) and multi-effect distillation (MED). However, some inherent technical issues, like high operation cost, large capital cost and/or low desalination capacity, associate with these existing technologies that lead to a high clean water production cost and limit their applications. Thus, there is a need of new water desalination technology that can purify saltwater with low cost and high efficiency. In this work we report a new water-soluble nickel phthalocyanine tetrasulfonic acid tetrasodium salt (NiPcTATS)-based redox flow desalination battery (RFDB) for safe, effective and efficient water-salt separation. The fabricated RFDB cell exhibited a high desalination rate at 3.4 gNaCl/(molNiPcTATS∙hr) even with a low 0.5 V cell voltage and required as low as 11.5 kJ/mol salt in energy consumption. The cell showed excellent reversibility and durability for long-term operation, benefiting from the fast-redox kinetics and chemical stability of the redox couple. With no consumption of the redox couple and energy recovery during the salination process, this new method provides a continuous desalination capability with unlimited salt removal capacity. We also demonstrated the use of simple solar panel for effectively driving the RFDB cell, proving it a promising and practical technology for clean water production in remote places like islands and ships.

Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning. Yet, it remains a challenge due to complexity of the growth process and technical limits of modern characterization tools. We report a combinational use of multiple cutting-edge in situ techniques to study the growth process of octahedral Pt3Ni nanoparticles, which reveal the particle growth and facet formation mechanisms. Our studies confirm the formation of octahedral Pt3Ni initiates from Pt nuclei generation, which is followed by continuous Pt reduction that simultaneously catalyzes Ni reduction, resulting in mixed alloy formation with moderate elemental segregation. Carbon monoxide molecules serve as a facet formation modulator and induce Ni segregation to the surface, which inhibits the (111) facet growth and causes the particle shape to evolve from a spherical cluster to an octahedron as the (001) facet continues to grow., Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning, but remains a challenge. Here, the authors reveal the particle growth and facet formation mechanisms of octahedral Pt3Ni nanoparticles using multiple cutting-edge in situ techniques.

Active sites play an essential role in heterogeneous catalysis and largely determine the reaction properties. Yet identification and study of the active sites remain challenging owing to their dynamic behaviors during catalysis process and issues with current characterization techniques. This article provides a short review of research progresses in active sites of metal and metal oxide catalysts, which covers the past achievements, current research status, and perspectives in this research field. In particular, the concepts and theories of active sites are introduced. Major experimental and computational approaches that are used in active site study are summarized, with their applications and limitations being discussed. An outlook of future research direction in both experimental and computational catalysis research is provided.

Subcellular localization is a main determinant of protein function; however, a global view of cellular proteome organization remains relatively unexplored. We have developed a robust mass spectrometry-based analysis pipeline to generate a proteome-wide view of subcellular localization for proteins mapping to 12,418 individual genes across five cell lines. Based on more than 83,000 unique classifications and correlation profiling, we investigate the effect of alternative splicing and protein domains on localization, complex member co-localization, cell-type-specific localization, as well as protein relocalization after growth factor inhibition. Our analysis provides information about the cellular architecture and complexity of the spatial organization of the proteome; we show that the majority of proteins have a single main subcellular location, that alternative splicing rarely affects subcellular location, and that cell types are best distinguished by expression of proteins exposed to the surrounding environment. The resource is freely accessible via www.subcellbarcode.org.

A novel methodology of maximum information entropy theory combined with structure oriented lumping (SOL) and Monte Carlo (MC) method was developed to simulate the feedstock for secondary reactions of fluid catalytic cracking (FCC) gasoline at the molecular level. The SOL method was applied to represent the feedstock configuration framework; a molecular library consisting of a large ensemble of computational molecules was created by stochastically assembling structural increments using MC method; then, the maximum information entropy method (MIEM) was introduced to adjust the mole fractions of the structural increments in the molecular library to achieve a closer matching with the actual analytical characteristics. Three samples of catalytic cracking gasoline from the industrial FCC units of China were used to validate and evaluate the proposed method. The simulation results of the feedstock properties, such as the average molecular weight and the weight fractions of main components including paraffin, olefins, naphthenes and aromatics agreed well with the experimental data.

Selective enrichment of specific peptides is an effective way to identify low abundance proteins. Fractionation of peptides prior to mass spectrometry is another widely used approach to reduce sample complexity in order to improve proteome coverage.In this study, we designed a multi-stage digestion strategy to generate peptides with different trypsin cleavage kinetics. It was found that each of the collected peptide fractions yielded many new protein identifications compared to the control group due to the reduced complexity. The overlapping peptides identified between adjacent fractions were very low, indicating that each fraction had different sets of peptides. The multi-stage digestion strategy separates tryptic peptides with different cleavage kinetics while RPLC separates peptides with different hydrophobicity. These two separation strategies were highly orthogonal, and showed an effective multidimensional separation to improve proteome coverage.

Polyacrylamide gel electrophoresis (PAGE) is a powerful protein separation technology. Combined with mass spectrometry, it could identify thousands of proteins in proteomics analysis. However, the time-consuming procedure restricts its broad applications in proteomics study. In this work, it was found that high concentration of trypsin did not compromise subsequent phosphopeptide enrichment after in-gel digestion, but could promote the in-gel digestion. Hence, a new, fast and robust digestion method was established. Firstly, 50 μg of HeLa cell protein was separated into 5 fractions by SDS-PAGE, and then the proteins were digested with high concentration trypsin for 30 min. Finally, the phosphopeptides were enriched by Ti-IMAC Tip. After liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, about 2000 phosphorylation sites were identified in the experimental group, while less than 1500 phosphorylation sites were identified in control group. With the aid of high concentration of trypsin, in-gel digestion could be completed within only 30 min, and more phosphorylation site identifications and lower percentage of missed cleavages were acquired than those in control experiments. The experiment results demonstrated that high concentration of trypsin could not only accelerate the in-gel digestion, but also improve the phosphoproteome coverage.

The reaction mechanism and properties of a catalytic process are primarily determined by the interactions between reacting species and catalysts. However, the interactions are often challenging to be experimentally measured, especially for unstable intermediates. Therefore, it is of significant importance to establish an exact relationship between chemical–catalyst interactions and catalyst parameters, which will allow calculation of these interactions and thus advance their mechanistic understanding. Herein we report the description of adsorption energy on transition metals by considering both ionic bonding and covalent bonding contributions and introduce the work function as one additional responsible parameter. We find that the adsorption energy can be more accurately described using a two-dimensional (2D) polynomial model, which shows a significant improvement compared with the current adsorption energy–d-band center linear correlation. We also demonstrate the utilization of this new 2D polynomial model to calculate oxygen binding energy of different transition metals to help understand their catalytic properties in oxygen reduction reactions.

Liquid–liquid equilibrium data for three ternary systems which contain glycerol and its etherification (tert-butylation) products including mono-tert-butyl ethers of glycerol (ME), di-tert-butyl ethers of glycerol (DE) and tri-tert-butyl ether of glycerol (TE) in the temperature range of 343.2–373.2 K under 101.3 kPa were obtained by phase equilibrium experiments. Reliability of the experimental data was verified by Othmer–Tobias equation. The non-random two liquid (NRTL) model was employed to describe the equilibrium compositions, and corresponding binary interaction parameters were estimated by data regression. The modeling results agreed well with measured data. In addition, three UNIFAC based methods were also adapted to model liquid–liquid equilibrium behavior for these systems; however, the predicted results emerged obvious deviation from experimental results.

An enzymatic approach to label peptide N-termini with isotope-coded affinity tags is presented. This method exploits the high activity of trypsin for peptide synthesis in organic solvents. A cosubstrate containing a stable isotope-coded Arg residue and a biotin tag was synthesized. When the cosubstrate was incubated with tryptic peptides and trypsin in ethanol solution, the stable isotope-coded affinity tag was specifically coupled onto the N-termini of peptides via the formation of new peptide bonds. The labeled peptides were specifically enriched by avidin affinity chromatography and then were submitted to liquid chromatography-tandem mass spectrometry (LC/MS/MS) for quantification. This enrichment step effectively reduced the interference by unlabeled peptides. The excellent performance of this approach was demonstrated by labeling standard peptides as well as a mouse liver digest. In addition to one amino acid residue, a few dipeptide tags were also introduced to the N-termini of peptides successfully by this enzymatic approach. It was found that the identifications for samples labeled with these tags were highly complementary. Coupling a short sequence tag onto peptides could be an effective approach to improve the coverage for proteome analysis.

The Ser/Thr protein kinases fall into three major subgroups, pro-directed, basophilic, and acidophilic, on the basis of the types of substrate sequences that they preferred. Despite many phosphoproteomics efforts that have been taken for global profiling of phosphopeptides, methodologies focusing on analyzing a particular type of kinase substrates have seldom been reported. Selective enrichment of phosphopeptides from basophilic kinase substrates is difficult because basophilic motifs are cleaved by trypsin during digestion. In this study, we develop a negative enrichment strategy to enhance the identification of basophilic kinase substrates. This method is based on an observation that high pH strong anion exchange (SAX) chromatography can separate tryptic phosphopeptides according to the number of acidic amino acidic residues that they have. Thus, SAX was applied to deplete acidic phosphopeptides from the phosphopeptide mixture, which improved the coverage for the detection of basophilic kinase substrates. The SAX depletion approach was further combined with online SCX-RP separation for large-scale analysis of mouse liver phosphoproteome, which resulted in the identification of 6944 phosphorylated sites. It was found that motifs associated with basophilic kinases prevail for these identified phosphorylated sites.

Material novelty is momentous for electrocatalyst in striding into a renewable energy era. Oxygen evolution reaction (OER) is of great significance for hydrogen production via water electrolysis, but has a high energy barrier that limits the energy conversion efficiency. Herein we report a highly-efficient and long-term durable NiFePB OER electrocatalyst, which composes of unique porous amorphous conductive solids with finely tuned nonmetal elements. The NiFePB phase formation is confirmed with X-ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS). X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) characterizations determine a porous amorphous structure. The outstanding metallic conductivity and corrosion resistance properties are simulated with density functional theory (DFT) calculations. Benefiting from these unique features, the NiFePB exhibits an extraordinarily low overpotential of 197 mV to reach an OER current density of 10 mA/cm2 and 233 mV to reach 100 mA/cm2 under chronopotentiometry condition, with the Tafel slope harmoniously conforming to 34 mV/dec. The catalyst also has an impressive long-term stability, evidenced by a limited activity decay for more than 50-h in a wide current density range from 10 to 200 mA/cm2. This work strategically directs a way for heading up a promising energy conversion alternative.