Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

Flexible silicon solar cells with high power-to-weight ratios.

Silicon solar cells are a mainstay of commercialized photovoltaics, and further improving the power conversion efficiency of large-area and flexible cells remains an important research objective1,2. Here we report a combined approach to improving the power conversion efficiency of silicon heterojunction solar cells, while at the same time rendering them flexible. We use low-damage continuous-plasma chemical vapour deposition to prevent epitaxy, self-restoring nanocrystalline sowing and vertical growth to develop doped contacts, and contact-free laser transfer printing to deposit low-shading grid lines. High-performance cells of various thicknesses (55-130 µm) are fabricated, with certified efficiencies of 26.06% (57 µm), 26.19% (74 µm), 26.50% (84 µm), 26.56% (106 µm) and 26.81% (125 µm). The wafer thinning not only lowers the weight and cost, but also facilitates the charge migration and separation. It is found that the 57-µm flexible and thin solar cell shows the highest power-to-weight ratio (1.9 W g-1) and open-circuit voltage (761 mV) compared to the thick ones. All of the solar cells characterized have an area of 274.4 cm2, and the cell components ensure reliability in potential-induced degradation and light-induced degradation ageing tests. This technological progress provides a practical basis for the commercialization of flexible, lightweight, low-cost and highly efficient solar cells, and the ability to bend or roll up crystalline silicon solar cells for travel is anticipated.

Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease. METHODS: Wire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype. RESULTS: Phenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation. CONCLUSIONS: The present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.

Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold.

Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.

Tudor-SN promotes cardiomyocyte proliferation and neonatal heart regeneration through regulating the phosphorylation of YAP.

BACKGROUND: The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury. METHODS: The Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN -/-) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo. RESULTS: We previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription. CONCLUSION: Tudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.

Influence of Imbibition Fracturing Fluid on the Original Water and Methane Occurrence in Actual Coalbed Methane Reservoirs Using the Integrated Device of Displacement and Low-Field Nuclear Magnetic Resonance.

The original water in the coal rock pores plays a controlling role in the occurrence of gas. Furthermore, during the hydraulic fracturing process, pressurized fracturing fluid with a higher pressure than the original pore pressure in the fractures drives the fracturing fluid to infiltrate into the coal rock pores, thereby altering the occurrence pattern of gas and water in the original pores. However, due to the limitations of the indoor simulation device, a systematic conclusion on the impact of the original pore water and imbibition fracturing fluid on coalbed methane reservoirs has not yet been formed. In this paper, an integrated device combining displacement and low-field nuclear magnetic resonance was employed using underground cylindrical coal rock samples as experimental subjects. Experimental conditions were maintained at a temperature of 30 °C, a confining pressure of 23 MPa, and an approximate reservoir pressure of 15 MPa. The initial water saturation levels were altered to 0, 27.88, and 42.18% to replicate the conditions of a coalbed methane reservoir at a depth of approximately 1200 m. Fracturing fluid with a pressure of 18 MPa was injected into the experimental samples to simulate the impact of the fracturing fluid on the original reservoir during hydraulic fracturing. This allowed for a realistic assessment of the influence of initial water saturation and fracturing fluid absorption on the coalbed methane recovery rate in the reservoir. The experimental results indicate that the imbibition process promotes the desorption of adsorbed gas, and the desorption amount of adsorbed gas increases with the increase in the original water saturation. This will result in an increase in the gas pressure within the pore system. The conditions of this experiment, in comparison to the previous ones, more closely resemble real reservoir conditions. This enables a realistic assessment of how the presence of the original water content and the absorption of the fracturing fluid affect gas occurrence within the reservoir.

Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

Pectin modifications at the symbiotic interface.

Plant cells are surrounded by a structured cell wall, which not only defines cell shape but also provides a structural barrier for protection against pathogen infection. However, the presence of this barrier does not impede the establishment of mutualistic symbioses between plants and several microbes (e.g. ectomycorrhizal fungi, arbuscular mycorrhizal fungi, and rhizobia). To establish such beneficial associations, symbiotic microbes need to colonize the plant tissues via intercellular and/or intracellular infection, a process that requires cell wall modifications. Although cell wall composition and changes during this process have interested researchers for years, the functional characterization of the molecular players involved is still limited. In this viewpoint, based on several new studies, I discuss how the PME-PL/PG pathway mediates cell wall pectin modifications at the symbiotic interface and highlight further research directions which can broaden our understanding of how beneficial root symbioses are established.

The Medicago truncatula DREPP Protein Triggers Microtubule Fragmentation in Membrane Nanodomains during Symbiotic Infections.

The initiation of intracellular host cell colonization by symbiotic rhizobia in Medicago truncatula requires repolarization of root hairs, including the rearrangement of cytoskeletal filaments. The molecular players governing microtubule (MT) reorganization during rhizobial infections remain to be discovered. Here, we identified M. truncatula DEVELOPMENTALLY REGULATED PLASMA MEMBRANE POLYPEPTIDE (DREPP), a member of the MT binding DREPP/PCaP protein family, and investigated its functions during rhizobial infections. We show that rhizobial colonization of drepp mutant roots as well as transgenic roots overexpressing DREPP is impaired. DREPP relocalizes into symbiosis-specific membrane nanodomains in a stimulus-dependent manner. This subcellular segregation coincides with DREPP-dependent MT fragmentation and a partial loss of the ability to reorganize the MT cytoskeleton in response to rhizobia, which might rely on an interaction between DREPP and the MT-organizing protein SPIRAL2. Taken together, our results reveal that establishment of symbiotic associations in M. truncatula requires DREPP in order to regulate MT reorganization during initial root hair responses to rhizobia.

High-dose VitC plus oncolytic adenoviruses enhance immunogenic tumor cell death and reprogram tumor immune microenvironment.

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.

Copy number variation of bovine S100A7 as a positional candidate affected body measurements.

Beef production is closely related to the national economy and the attention has been paid to the improvement of beef cattle by molecular markers associated. Copy number variations (CNVs) recently have been gained many researches and recognized as an important source of genetic variation. Extensive studies have indicated that CNVs have effects on a large range of economic traits by a wide range of gene copy number alteration. S100A7 is a member of S100 family which is a famous family of Ca2+-binding proteins. S100A7 plays a crucial role in many important phenotypes (progress) including inflammatory diseases, psoriasis, obesity, etc. The aim of our study was to explore the phenotypic effects of CNV located in the S100A7 gene of bovine chromosome 3. We detected S100A7 CNV by qPCR in different cattle breeds, including Qinchuan cattle, Yunling cattle, Xianan cattle and a crossbred group Pinan. The copy number was identified as gain, normal and loss type, our results showed that the gain type was the main type in three types of S100A7 CNV of the whole tested breeds. After CNV detection, association analysis between S100A7 CNV and growth traits was carried out in four cattle breeds. We found significant effects of the CNV on cattle growth traits with differently preferred CNV types such as gain type with better chest depth (p = 0.043) in QC, loss type with better body length (p = 0.008) and rump width (p = 0.014) in YL, normal with better chest girth (p = 0.001), gain with better waist width (p = 0.001) and rump width (p = 0.044) in PN. These results suggested that the S100A7 CNV could affect the phenotypic traits and be used as a promising genetic marker for cattle molecular breeding.

ACL stump and ACL femoral landmarks are equally reliable in ACL reconstruction for assisting ACL femoral tunnel positioning.

PURPOSE: This study aimed to comparatively evaluate the accuracy of femoral tunnel positioning after anatomic single-bundle anterior cruciate ligament (ACL) reconstruction performed with the remnant preservation (RP) technique versus the non-remnant preservation (NRP) technique. METHODS: A retrospective review of 145 patients who underwent ACL reconstruction from May 2020 to May 2022 were performed in this single-surgeon study. A total of 120 patients met the inclusion criteria and were allocated into two groups according to the surgical technique (i.e. RP group and NRP group). The relative location of the femoral tunnel in the lateral condyle was evaluated as a percentage using a standardized grid system on the three-dimensional computed tomography (3D-CT) image. The accuracy and precision of the RP group were assessed based on published anatomical data in direct comparison with the NRP group. RESULTS: According to the surgical procedure, 57 of the 120 patients included were allocated into the RP group, and 63 into the NRP group. Significant differences were observed between the two groups in terms of tunnel position (posterior-to-distal (PD): 28.4 ± 5.4% (RP) vs. 31.8 ± 5.3% (NRP); P = 0.01), (anterior-to-posterior (AP): 32.6 ± 7.7% (RP) vs. 38.8 ± 7.7% (NRP); P = 0.00), while no significant differences were found in terms of the accuracy (8.6% (RP) vs. 8.9% (NRP); n.s) and precision (4.4% (RP) vs. 5.6% (NRP); n.s) of femoral tunnel positioning between the two groups. CONCLUSIONS: From this single-surgeon study, it was concluded that there were no differences in the creation of ACL femoral tunnel between the RP technique and the non-remnant preserving technique. Meanwhile, the RP technique would not sacrifice the ideal position of the femoral tunnel and is able to retain the possible benefits of the ACL stump. LEVEL OF EVIDENCE: Level III.

Ammonium-Amine Co-Activation: Promoting the Sulfurization of Azurite and Its Effect on Xanthate Adsorption.

Enhanced sulfurization has always been the focus of research on the flotation of copper oxide minerals. In this study, combined ammonium-amine salts were innovatively applied to improve the sulfurization of azurite. Flotation tests were carried out to evaluate the promoting effect of ammonium-amine co-activation on the sulfurization-xanthate flotation of azurite, and the microstructure evolution of sulfurized products was investigated to reveal the mechanism underlying this promoting effect. Compared with single ammonium (amine) salt activation, ammonium-amine co-activation improved the floatability of azurite to a greater extent, i.e., the flotation recovery increased by over 4 percentage points. ToF-SIMS, ICP-OES, FESEM-EDS, AFM, XRD, and UV-vis analyses indicated that ammonium-amine co-activation combined the advantages of inorganic ammonium for buffering pH and organic amine for copper ion complexation, thus promoting the growth of sulfurized crystal products (covellite) and enhancing the adhesion stability of sulfurized products on azurite. Therefore, increasing amounts of copper sulfide components were generated under the ammonium-amine-Na2S system, promoting the adsorption of additional xanthate on azurite. This study provides theoretical support for the application of combined ammonium-amine salts for the sulfurization flotation of copper oxide.

Fluoropolymer: A Review on Its Emulsion Preparation and Wettability to Solid-Liquid Interface.

In the preparation of a superamphiphobic surface, the most basic method is to reduce the surface free energy of the interface. The C-F bond has a very low surface free energy, which can significantly change the wettability of the solid-liquid interface and make it a hydrophobic or oleophobic, or even superamphiphobic surface. Based on the analysis of a large number of research articles, the preparation and application progress in fluoropolymer emulsion were summarized. After that, some corresponding thoughts were put forward combined with our professional characteristics. According to recent research, the status of the fluoropolymer emulsion preparation system was analyzed. In addition, all related aspects of fluoropolymer emulsion were systematically classified in varying degrees. Furthermore, the interaction between fluoropolymer structure and properties, especially the interaction with nanomaterials, was also explored. The aim of this review is to try to attract more scholars' attention to fluorocarbon interfacial materials. It is expected that it will make a certain theoretical and practical significance in the preparation and application of fluoropolymer.

Synthesis, Performance, Mechanism: A Hyperbranched Phase Reverse Nano-Demulsifier for Condensate Emulsion.

Organic amine and nanosilica were combined to create a nano-demulsifier, which was employed in the oil-water separation process of a condensate emulsion. The nano-demulsifier has the structure of hyperbranched polymers and the skeleton structure of hyperbranched nanomaterials, and displays the demulsification impact of organic amine polymers as well as the synergistic effect of nanomaterials. This nano-demulsifier has the potential to drastically reduce the quantity of condensate demulsifiers utilized in the gathering station. The dehydration rate of the condensate lotion in the gas gathering station can reach more than 95% only at a concentration of 1.0 wt.%. Its application can significantly increase the separation efficiency of the condensate emulsion as well as the quality of condensate oil. It has a positive impact on cost reduction and efficiency in gas well production. The mechanism of action of the demulsifier was also studied, and the results show that the demulsifier is a phase reverse demulsifier.

Distribution and transfer rules of polycyclic aromatic hydrocarbons in soil-wheat ecosystems in China.

The translocation and accumulation patterns of polycyclic aromatic hydrocarbons (PAHs) in the soil-crop system have important implications for the fate of PAHs and human health. This study summarized the concentrations of 16 priority PAHs in the soils and various parts of mature winter wheat in China, sourced from a screening of previous literature in English and Chinese databases. The study analyzes the distribution characteristics, transfer patterns, and human health risks of PAHs in sites studied in Shaanxi, Henan, and Shandong provinces. The results showed that the concentrations of Σ16 PAHs in the rhizosphere soil of wheat ranged from 10.30 to 893.68 ng/g, in descending order of Shaanxi > Henan > average > Shandong. In sites with mild to moderate contamination (200 < Σ16 PAHs < 600 ng/g; i.e., Henan and Shaanxi), the concentration of Σ16 PAHs in the roots was higher than that in the stems or the grains, while in contamination-free sites (Σ16 PAHs < 200 ng/g; i.e., Shandong), the highest concentration of Σ16 PAHs was found in the stems. Generally, the concentrations of PAHs increased in the order of roots-stems-grains. The predominant PAHs in each part of wheat were 2- or 3-ring compounds, with five- or six-ring PAHs being more prevalent in wheat from Shanghe, Shandong. The bioaccumulation factors of different wheat parts from Shaanxi and Henan were consistently smaller than 1, and low- and medium-ring (2-4 rings) PAHs had bigger bioconcentration factors than high-ring (5-6 rings) PAHs. However, the accumulation of PAHs in the aboveground parts of wheat was larger than that in the underground parts of the Shandong sites. The linear regression relationship between the octanol-water partition coefficient and root concentration factor (RCF) of PAHs reflected that low and medium-ring PAHs were more easily absorbed by wheat roots than high-ring PAHs in Shaanxi and Henan. Our assessment of the health risks of oral wheat intake in adults and children by the incremental lifetime cancer risk (ILCR) model found a potential carcinogenic risk for both age groups in each province, with higher risks in adults than in children.

Highly Efficient Visible-Light-Driven CO2-to-CO Conversion by Coordinatively Unsaturated Co-Salen Complexes in a Water-Containing System.

The development of cost-effective catalysts for CO2 reduction is highly desired but remains a significant challenge. The unsaturated coordination metal center in a catalyst is favorable for the process of catalytic CO2 reduction. In this paper, two asymmetric salen ligands were used to synthesize two coordinatively unsaturated Co-salen complexes. The two Co-salen complexes exhibit an unsaturated coordination pattern and display high activity and CO selectivity for visible-light-driven CO2 reduction in a water-containing system. The photocatalytic performance of 2 is higher than that of 1 because the reduction potential of the catalytic CoII center and the energy barrier of the catalytic transition states of 2 are lower than those of 1, with turnover numbers (TONCO), turnover frequencies (TOF), and CO selectivity values of 8640, 0.24 s-1, and 97% for 2, respectively. The photocatalytic reduction of CO2 to CO for 2 is well supported by control experiments and density functional theory (DFT) calculations.

Systematic use of synthetic 5'-UTR RNA structures to tune protein translation improves yield and quality of complex proteins in mammalian cell factories.

Predictably regulating protein expression levels to improve recombinant protein production has become an important tool, but is still rarely applied to engineer mammalian cells. We therefore sought to set-up an easy-to-implement toolbox to facilitate fast and reliable regulation of protein expression in mammalian cells by introducing defined RNA hairpins, termed 'regulation elements (RgE)', in the 5'-untranslated region (UTR) to impact translation efficiency. RgEs varying in thermodynamic stability, GC-content and position were added to the 5'-UTR of a fluorescent reporter gene. Predictable translation dosage over two orders of magnitude in mammalian cell lines of hamster and human origin was confirmed by flow cytometry. Tuning heavy chain expression of an IgG with the RgEs to various levels eventually resulted in up to 3.5-fold increased titers and fewer IgG aggregates and fragments in CHO cells. Co-expression of a therapeutic Arylsulfatase-A with RgE-tuned levels of the required helper factor SUMF1 demonstrated that the maximum specific sulfatase activity was already attained at lower SUMF1 expression levels, while specific production rates steadily decreased with increasing helper expression. In summary, we show that defined 5'-UTR RNA-structures represent a valid tool to systematically tune protein expression levels in mammalian cells and eventually help to optimize recombinant protein expression.

Emerging two-dimensional nanomaterials for electrochemical nitrogen reduction.

Ammonia (NH3) is essential to serve as the biological building blocks for maintaining organism function, and as the indispensable nitrogenous fertilizers for increasing the yield of nutritious crops. The current Haber-Bosch process for industrial NH3 production is highly energy- and capital-intensive. In light of this, the electroreduction of nitrogen (N2) into valuable NH3, as an alternative, offers a sustainable pathway for the Haber-Bosch transition, because it utilizes renewable electricity and operates under ambient conditions. Identifying highly efficient electrocatalysts remains the priority in the electrochemical nitrogen reduction reaction (NRR), marking superior selectivity, activity, and stability. Two-dimensional (2D) nanomaterials with sufficient exposed active sites, high specific surface area, good conductivity, rich surface defects, and easily tunable electronic properties hold great promise for the adsorption and activation of nitrogen towards sustainable NRR. Therefore, this Review focuses on the fundamental principles and the key metrics being pursued in NRR. Based on the fundamental understanding, the recent efforts devoted to engineering protocols for constructing 2D electrocatalysts towards NRR are presented. Then, the state-of-the-art 2D electrocatalysts for N2 reduction to NH3 are summarized, aiming at providing a comprehensive overview of the structure-performance relationships of 2D electrocatalysts towards NRR. Finally, we propose the challenges and future outlook in this prospective area.