Conformational Toggling of Yeast Iso-1-Cytochrome c in the Oxidized and Reduced States

To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50–102) presents a kind of “zigzag riveting ruler” structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50–102), to prevent heme pocket from the solvent

Fast Synthesis of Organic Copper Halide Crystals for X-ray Imaging

Copper-based metal halides are a group of potential scintillation materials with non-toxic and environmentally friendly properties. However, the slow growth rate of their crystals hinders their applications. In this paper, an organic [N(C2H5)4]2Cu2Br4 crystal was proposed for X-ray scintillation imaging. It was successfully synthesized using a fast solution-phased approach with a production rate of 100 mg/min. The photoluminescence quantum yield of the [N(C2H5)4]2Cu2Br4 crystal is 55% with good stability. More importantly, it has a bright blue emission with a large Stokes shift originating from self-trapped excitons, which contribute to the reabsorption-free characteristic. Its scintillation properties, with a light yield of 7623 photons MeV−1 and remarkable X-ray imaging performance, provide important guidance for the further study of X-ray scintillation crystals

A Virtual Channel Allocation Algorithm for NoC

Virtual channel (VC) flow control proves to be an alternative way to promote network performance, but uniform VC allocation in the network may be at the cost of chip area and power consumption. We propose a novel VC number allocation algorithm customizing the VCs in network based on the characteristic of the target application. Given the characteristic of target application and total VC number budget, the block probability for each port of nodes in the network can be obtained with an analytical model. Then VCs are added to the port with the highest block probability one by one. The simulation results indicate that the proposed algorithm reduces buffer consumption by 14.58%~51.04% under diverse traffic patterns and VC depth, while keeping similar network performance

Functional Conversion of Acetyl-Coenzyme a Synthase to a Nickel Superoxide Dismutase via Rational Design of Coordination Microenvironment for the Nid-Site

The Nid site coordination microenvironment of a truncated acetyl-coenzyme A synthase has been designed systematically for functional conversion to a Ni-SOD-like enzyme. To this end, the first strategy is to introduce an axial histidine ligand, using mutations F598H, S594H and S594H-GP individually. The resulting three mutants obtained Ni-SOD-like activity successfully, although the catalytic activity was about 10-fold lower than in native Ni-SOD. The second strategy is to mimic the H-bond network in the second sphere coordination microenvironment of the native Ni-SOD. Two mutations based on F598H (EFG-F598H and YGP-F598H) were designed. The successful EFG-F598H exhibited ~3-fold Ni-SOD-like activity of F598H. These designed Ni-SOD-like metalloproteins were characterized by UV/Vis, EPR and Cyclic voltammetry while F598H was also characterized by X-ray protein crystallography. The pH titrations were performed to reveal the source of the two protons required for forming H2O2 in the SOD catalytic reaction. Based on all of the results, a proposed catalytic mechanism for the Ni-SOD-like metalloproteins is presented

Dynamic surveillance of SARS-CoV-2 shedding and neutralizing antibody in children with COVID-19

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and quickly spread globally. In this study, we investigated the characteristics of viral shedding from different sites and the neutralizing antibody (NAb) response during the acute and convalescent phases of nine children with COVID-19. SARS-CoV-2 was detected in their nasopharyngeal swabs (9/9, 100%), stool samples (8/9, 89%), and oropharyngeal swabs (3/9, 33%) but was not detected in their serum and urine samples. The median duration of viral shedding detected in nasopharyngeal swabs, oropharyngeal swabs, and stools was 13, 4, and 43 days respectively, and the maximum duration of viral shedding detected from stools was 46 days after discharge. In children, nasopharyngeal swabs appear to be a more sensitive specimen type for the diagnosis of COVID-19 compared with oropharyngeal swabs. Three of eight patients produced NAbs in the acute phase, and NAbs were detected in all eight patients with convalescent sera. The results of this study provide valuable information for the diagnosis and surveillance of COVID-19 and development of SARS-CoV-2 vaccines for use in children

Selective Furfuryl Alcohol Production from Furfural via Bio-Electrocatalysis

The catalytic reduction of renewable furfural into furfuryl alcohol for various applications is in the ascendant. Nonetheless, the conventional chemo-catalysis hydrogenation of furfural always suffers from poor selectivity, harsh conditions, and expensive catalysts. Herein, to overcome the serious technical barriers of conventional furfuryl alcohol production, an alternative bio-electrocatalytic hydrogenation system was established under mild and neutral conditions, where the dissolved cofactor (NADH) and the alcohol dehydrogenase (ADH) participated in a tandem reaction driven by the electron from a novel Rh (III) complex fixed cathode. Under the optimized conditions, 81.5% of furfural alcohol selectivity can be realized at −0.43 V vs. RHE. This contribution presents a ‘green’ and promising route for the valorization of furfural and other biomass compounds

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells

Steady-state kinetics studies on (A) heme destruction and (B) peroxidase activity vs pH change of wild-type cyt <i>c</i> and its Y67H mutant.

<p>Steady-state kinetics studies on (A) heme destruction and (B) peroxidase activity vs pH change of wild-type cyt <i>c</i> and its Y67H mutant.</p

Structure of the heme region of cyt <i>c</i> and the location of Tyr67 in the structure (pdb code: 1YIC), showing the hydrogen bond network formed by amino acids His18, Tyr67, Met80, Asn52 and Thr78.

<p>Structure of the heme region of cyt <i>c</i> and the location of Tyr67 in the structure (pdb code: 1YIC), showing the hydrogen bond network formed by amino acids His18, Tyr67, Met80, Asn52 and Thr78.</p