Highly Active Trimetallic NiFeCr Layered Double Hydroxide Electrocatalysts for Oxygen Evolution Reaction

The development of efficient and robust earth‐abundant electrocatalysts for the oxygen evolution reaction (OER) is an ongoing challenge. Here, a novel and stable trimetallic NiFeCr layered double hydroxide (LDH) electrocatalyst for improving OER kinetics is rationally designed and synthesized. Electrochemical testing of a series of trimetallic NiFeCr LDH materials at similar catalyst loading and electrochemical surface area shows that the molar ratio Ni:Fe:Cr = 6:2:1 exhibits the best intrinsic OER catalytic activity compared to other NiFeCr LDH compositions. Furthermore, these nanostructures are directly grown on conductive carbon paper for a high surface area 3D electrode that can achieve a catalytic current density of 25 mA cm^?2 at an overpotential as low as 225 mV and a small Tafel slope of 69 mV dec^?1 in alkaline electrolyte. The optimized NiFeCr catalyst is stable under OER conditions and X‐ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and elemental analysis confirm the stability of trimetallic NiFeCr LDH after electrochemical testing. Due to the synergistic interactions among the metal centers, trimetallic NiFeCr LDH is significantly more active than NiFe LDH and among the most active OER catalysts to date. This work also presents general strategies to design more efficient metal oxide/hydroxide OER electrocatalysts.     

人白介素6受体结合功能域的构效关系研究

以分子对接（docking）方法研究人白介素6受体胞外区配基结合功能域“WSXWS”区氨基酸残基定点突变对受体与配基人白介素6结合时的相互作用能量、分子间相互作用的影响,从分子力学、分子动态学分析了人白介素6受体胞外区功能域关键氨基酸残基在受体与配基结合中的构象变化以及与人白介素6间的相互作用.     

固定云芝漆酶纳米金颗粒修饰金盘电极的制备及其对氧还原反应的生物电催化性能

利用1,6-己二硫醇作为联结剂将纳米金颗粒修饰到金盘电极上,再以L-半胱氨酸为修饰剂使纳米金颗粒功能化并进一步与漆酶充分作用,制备了固定漆酶的纳米金颗粒修饰金盘电极并以循环伏安法测试了其对氧还原的催化性能。实验结果表明:O2在该电极上还原电位约为-0.26 V(vs SCE),氧还原峰电流为3.0 uA(25℃),较文献[7]报导的固酶聚异丙基丙烯酰胺(PNIPAM)水凝胶修饰ITO电极的氧还原催化性能要优。(氧气还原电位:-0.26 V,vs NHE,峰电流:0.47 uA)进一步研究表明:本文制备的修饰电极稳定性好,适于长期使用而且热稳定性优于文献[7]报道的固酶聚异丙基丙烯酰胺水凝胶修饰ITO电极:50℃时在本文制备的纳米金修饰电极上氧还原峰电流仍保持为25℃时修饰电极上氧还原峰电流的40%左右。     

Structure,energetics and properties of some molecules with potent anti-HIV activity: a theoretical study

Density functional theory (DFT; B3LYP) and Hartree–Fock (HF; 3-21G, 6-31G(d) and 6-311G(d,p)) calculations with complete geometry optimisations are carried out in the ground state on five 6-aminoquinolone derivatives, which have been proved to be highly effective in inhibiting HIV replication, to study their structures, energetics and HOMO–LUMO correlation with physiological action. The gas-phase calculations and single-point polarisable continuum model water-phase calculations show that the molecules are highly effective in inhibiting HIV replication, which is in excellent agreement with the experiment. Structural features, energies, charge densities and HOMO–LUMO correlation have been found to substantiate the experimental findings. Compound 4 (pyrazine) shows some special features in DFT calculations which are not found in HF calculations. In the present series, HF results are more reliable as expected.     

Identification of Redox Partners and Development of a Novel Chimeric Bacterial Nitric Oxide Synthase for Structure Activity Analyses

Production of nitric oxide (NO) by nitric oxide synthase (NOS) requires electrons to reduce the heme iron for substrate oxidation. Both FAD and FMN flavin groups mediate the transfer of NADPH derived electrons to NOS. Unlike mammalian NOS that contain both FAD and FMN binding domains within a single polypeptide chain, bacterial NOS is only composed of an oxygenase domain and must rely on separate redox partners for electron transfer and subsequent activity. Here, we report on the native redox partners for Bacillus subtilis NOS (bsNOS) and a novel chimera that promotes bsNOS activity. By identifying and characterizing native redox partners, we were also able to establish a robust enzyme assay for measuring bsNOS activity and inhibition. This assay was used to evaluate a series of established NOS inhibitors. Using the new assay for screening small molecules led to the identification of several potent inhibitors for which bsNOS-inhibitor crystal structures were determined. In addition to characterizing potent bsNOS inhibitors, substrate binding was also analyzed using isothermal titration calorimetry giving the first detailed thermodynamic analysis of substrate binding to NOS.     

A Composite Gel Polymer Electrolyte with High Performance Based on Poly(Vinylidene Fluoride) and Polyborate for Lithium Ion Batteries

A composite membrane based on electrospun poly(vinylidene fluoride) (PVDF) and lithium polyvinyl alcohol oxalate borate (LiPVAOB) exhibiting high safety (self‐extinguishing) and good mechanical property is prepared. The ionic conductivity of the as‐prepared gel polymer electrolyte from this composite membrane saturated with 1 mol L^?1 LiPF₆ electrolyte at ambient temperature can be up to 0.26 mS cm^?1, higher than that of the corresponding well‐used commercial separator (Celgard 2730), 0.21 mS cm^?1. Moreover, the lithium ion transference in the gel polymer electrolyte at room temperature is 0.58, twice as that in the commercial separator (0.27). Furthermore, the absorbed electrolyte solvent is difficult to evaporate at elevated temperature. Its electrochemical performance is evaluated by using LiFePO₄ cathode. The obtained results suggest that this gel‐type composite membrane shows great possibilities for use in large‐capacity lithium ion batteries that require high safety.     

The Hexameric Structure of a Conjugative VirB4 Protein ATPase Provides New Insights for a Functional and Phylogenetic Relationship with DNA Translocases

VirB4 proteins are ATPases essential for pilus biogenesis and protein transport in type IV secretion systems. These proteins contain a motor domain that shares structural similarities with the motor domains of DNA translocases, such as the VirD4/TrwB conjugative coupling proteins and the chromosome segregation pump FtsK. Here, we report the three-dimensional structure of full-length TrwK, the VirB4 homologue in the conjugative plasmid R388, determined by single-particle electron microscopy. The structure consists of a hexameric double ring with a barrel-shaped structure. The C-terminal half of VirB4 proteins shares a striking structural similarity with the DNA translocase TrwB. Docking the atomic coordinates of the crystal structures of TrwB and FtsK into the EM map revealed a better fit for FtsK. Interestingly, we have found that like TrwB, TrwK is able to bind DNA with a higher affinity for G4 quadruplex structures than for single-stranded DNA. Furthermore, TrwK exerts a dominant negative effect on the ATPase activity of TrwB, which reflects an interaction between the two proteins. Our studies provide new insights into the structure-function relationship and the evolution of these DNA and protein translocases.     

Myristoylation of EV71 VP4 is Essential for Infectivity and Interaction with Membrane Structure

Virologica Sinica - The Enterovirus 71 (EV71) VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue. However, the role of this myristoylation in the EV71 life...     

温度对双低两用核不育水稻96-5-2S与培矮64S育性的影响

在自然变温、人工控温及冷水灌溉条件下,比较研究了温度对双低两用核不育水稻96－5－2S与两用核不育水稻培矮64S育性影响的差异。结果表明：（1）当它们在雄性育性转换温敏感期1－12d平均自然日均温23.0-23.8℃的低温时,96－5－2S表现不良,套袋自交结实率为0,而培矮46S可育,套袋自交结实率为0．1％－4．5％;（2）在它们雄性育性转换温敏感期用22℃恒温处理5d,96－5－2S败育彻底,套袋自交结实率为0,而培矮64S可育,套袋自交结实率为10．7％;用17℃恒温处理6d,96－5－2S与培矮64S均可育,但96－5－2S套袋自交结实率（6．8％）显著高于培矮64S（2．5％）;（3）在它们雄性育性转换温和不同温度的冷水串灌15d,水深维持在20cm左右,当水温为22－22．5℃时,96－5－2S不育,结实率为0,而培矮64S可育,结实率为18．5％;当水温为19．5－21．5℃时,96－5－2S与培矮64S均可育,但96－5－2S结实率（2．5％－45．1％）显著或极显著低于培矮64S（50．4％－56．9％）以上结果说明：导致双低两用核不育水稻96－5－2S雄性不育的起点温度与导致其生理不育的下限温度均低,其不育性比培矮64S更稳定,耐寒性比培矮64S更强,即可确保制种安全,又可确保自身繁殖,对加快两系法杂交水稻的发展步伐将起到重要的促进作用。     

Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. Importantly, it also prevented Nox4 recruitment to SHPS-1. The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. These findings provide insight into the mechanism by which localized Nox4-derived ROS regulates the sustained activity of a tyrosine kinase that is critical for mediating signal transduction and biological actions.     

Highly Active and Stable Graphene Tubes Decorated with FeCoNi Alloy Nanoparticles via a Template‐Free Graphitization for Bifunctional Oxygen Reduction and Evolution

Development of highly active and stable bifunctional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysts from earth‐abundant elements remains a grand challenge for highly demanded reversible fuel cells and metal–air batteries. Carbon catalysts have many advantages over others due to their low cost, excellent electrical conductivity, high surface area, and easy functionalization. However, they typically cannot withstand the highly oxidative OER environment. Here, a new class of bifunctional electrocatalyst is reported, consisting of ultralarge sized nitrogen doped graphene tubes (N‐GTs) (>500 nm) decorated with FeCoNi alloy particles. These tubes are prepared from an inexpensive precursor, dicyandiamide, via a template‐free graphitization process. The ORR/OER activity and the stability of these graphene tube catalysts depend strongly on the transition metal precursors. The best performing FeCoNi‐derived N‐GT catalyst exhibits excellent ORR and OER activity along with adequate electrochemical durability over a wide potential window (0–1.9 V) in alkaline media. The measured OER current is solely due to desirable O₂ evolution, rather than carbon oxidation. Extensive electrochemical and physical characterization indicated that high graphitization degree, thicker tube walls, proper nitrogen doping, and presence of FeCoNi alloy particles are vital for high bifunctional activity and electrochemical durability of tubular carbon catalysts.     

Superior Multifunctional Activity of Nanoporous Carbons with Widely Tunable Porosity: Enhanced Storage Capacities for Carbon‐Dioxide,Hydrogen, Water,and Electric Charge

Nanoporous carbons (NPCs) with engineered specific pore sizes and sufficiently high porosities (both specific surface area and pore volume) are necessary for storing energy in the form of electric charges and molecules. Herein, NPCs, derived from biomass pine‐cones, coffee‐grounds, graphene‐oxide and metal‐organic frameworks, with systematically increased pore width (<1.0 nm to a few nm), micropore volume (0.2–0.9 cm³ g^?1) and specific surface area (800–2800 m² g^?1) are presented. Superior CO₂, H_2, and H₂O uptakes of 35.0 wt% (≈7.9 mmol g^?1 at 273 K), 3.0 wt% (at 77 K) and 85.0 wt% (at 298 K), respectively at 1 bar, are achieved. At controlled microporosity, supercapacitors deliver impressive performance with a capacity of 320 and 230 F g^?1 at 500 mA g^?1, in aqueous and organic electrolytes, respectively. Excellent areal capacitance and energy density (>50 Wh kg^?1 at high power density, 1000 W kg^?1) are achieved to form the highest reported values among the range of carbons in the literature. The noteworthy energy storage performance of the NPCs for all five cases (CO₂, H₂, H₂O, and capacitance in aqueous and organic electrolytes) is highlighted by direct comparison to numerous existing porous solids. A further analysis on the specific pore type governed physisorption capacities is presented.     

Interface Engineering of MXene Composite Separator for High‐Performance Li–Se and Na–Se Batteries

Selenium (Se), due to its high electronic conductivity and high energy density, has recently attracted considerable interest as a cathode material for rechargeable Li/Na batteries. However, the poor cycling stability originating from the severe shuttle effect of polyselenides hinders their practical applications. Herein, highly stable Li/Na–Se batteries are developed using ultrathin (≈270 nm, loading of 0.09 mg cm^?2) cetrimonium bromide (CTAB)/carbon nanotube (CNT)/Ti₃C₂T_x MXene hybrid modified polypropylene (PP) (CCNT/MXene/PP) separators. The hybrid separator can immobilize the polyselenides via enhanced Lewis acid–base interactions between CTAB/MXene and polyselenides, which is demonstrated by theoretical calculations and X‐ray photoelectron spectroscopy. The incorporation of CNT helps to improve the electrolyte infiltration and facilitate the ionic transport. In situ permeation experiments are conducted for the first time to visually study the behavior of polyselenides, revealing the prohibited shuttle effect and protected Li anode from corrosion with CCNT/MXene/PP separators. As a result, the Li–Se batteries with CCNT/MXene/PP separators deliver an outstanding cycling performance over 500 cycles at 1C with an extremely low capacity decay of 0.05% per cycle. Moreover, the hybrid separators also perform well in Na–Se batteries. This study develops a preferable separator–electrolyte interface and the concept can be applied in other conversion‐type battery systems.     

The Mitosis and Neurodevelopment Proteins NDE1 and NDEL1 Form Dimers, Tetramers, and Polymers with a Folded Back Structure in Solution

Paralogs NDE1 (nuclear distribution element 1) and NDEL1 (NDE-like 1) are essential for mitosis and neurodevelopment. Both proteins are predicted to have similar structures, based upon high sequence similarity, and they co-complex in mammalian cells. X-ray diffraction studies and homology modeling suggest that their N-terminal regions (residues 8–167) adopt continuous, extended α-helical coiled-coil structures, but no experimentally derived information on the structure of their C-terminal regions or the architecture of the full-length proteins is available. In the case of NDE1, no biophysical data exists. Here we characterize the structural architecture of both full-length proteins utilizing negative stain electron microscopy along with our established paradigm of chemical cross-linking followed by tryptic digestion, mass spectrometry, and database searching, which we enhance using isotope labeling for mixed NDE1-NDEL1. We determined that full-length NDE1 forms needle-like dimers and tetramers in solution, similar to crystal structures of NDEL1, as well as chain-like end-to-end polymers. The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 (disrupted-in-schizophrenia 1), includes a predicted disordered region that allows a bent back structure. This facilitates interaction of the C-terminal region with the N-terminal coiled-coil domain and is in agreement with previous results showing N- and C-terminal regions of NDEL1 and NDE1 cooperating in dynein interaction. It sheds light on recently identified mutations in the NDE1 gene that cause truncation of the encoded protein. Additionally, analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly.     

A Transmissible Cytotoxic Activity Isolated from a Patient with Brain Ischemia Causes Microglial Cell Activation and Dysfunction

Summary 1. Microglial cell activation occurs during brain injury, ischemia, and in several neurologic disorders. Recently, we isolated a transmissible cytotoxic activity (TCA) from the cerebrospinal fluid of a patient with brain ischemia. Such a TCA, associated with one or more protein(s) that supposedly had undergone in vivo misfolding, causes apoptosis in vitro in different cell lines, including microglial cells. The TCA producing cells and the potential in vivo role of such cytotoxic activity remains to be elucidated. Here, we investigated the in vitro effects of TCA on microglial cell immune functions. 2. The murine microglial cell line RR4 was exposed to TCA, and then its response was evaluated as: (a) phagocytosis and antifungal activity against Candida albicans; (b) secretory pattern; and (c) levels of p38 phosphorylation. 3. Unlike mock-treated controls, microglial cells exposed to TCA showed an increase in phagocytic activity. Unexpectedly, their capability to kill the ingested fungi significantly diminished. Moreover, TCA-treated cells produced amounts of macrophage inflammatory protein 1-α, tumor necrosis factor-α, and nitric oxide significantly higher than mock-treated cells. Finally, phosphorylation of p38 mitogen-activated protein kinase (MAPK) was detected in TCA-treated but not in mock-treated controls as early as 30 min after treatment. 4. Overall, these results indicate that TCA causes a rapid molecular response in microglial cells, by the time, leading to an intriguing effector and secretory dysfunction.     

Formation and Structure of a NAIP5-NLRC4 Inflammasome Induced by Direct Interactions with Conserved N- and C-terminal Regions of Flagellin

The NOD-like receptors NAIP5 and NLRC4 play an essential role in the innate immune response to the bacterial tail protein flagellin. Upon flagellin detection, NAIP5 and NLRC4 form a hetero-oligomeric inflammasome that induces caspase-1-dependent cell death. So far, both the mechanism of formation of the NAIP5-NLRC4 inflammasome and its structure are poorly understood. In this study we combine inflammasome reconstitution in HEK293 cells, purification of inflammasome components, and negative stain electron microscopy to address these issues. We find that a Salmonella typhimurium flagellin fragment comprising the D0 domain and the neighboring spoke region is able to co-precipitate NAIP5 and induce formation of the NAIP5-NLRC4 inflammasome. Comparison with smaller fragments indicates that flagellin recognition is mediated by its C-terminal residues as well as the spoke region. We reconstitute the inflammasome from purified flagellin, NAIP5, and NLRC4, thus proving that no other cellular components are required for its formation. Electron micrographs of the purified inflammasome provide unprecedented insight into its architecture, revealing disk-like complexes consisting of 11 or 12 protomers in which NAIP5 and NLRC4 appear to occupy equivalent positions. On the basis of our data, we propose a model for inflammasome formation wherein direct interaction of flagellin with a single NAIP5 induces the recruitment and progressive incorporation of NLRC4, resulting in the formation of a hetero-oligomeric inflammasome.     

表达量高、血凝活性好的H3N2流感病毒血凝素（HA）蛋白疫苗的筛选研究

摘要 目的：筛选表达量高、血凝活性好的H3N2流感病毒血凝素（HA）重组蛋白。方法：以A/MINNESOTA/41/2019（H3N2）毒株的HA为基础,将HA胞外区N端融合GP67信号肽,C端融合三聚化基序,分别构建HA胞外区全长及近膜区截短2个氨基酸的HA重组杆状病毒,并构建相应的不含三聚化基序的HA重组杆状病毒;经昆虫细胞表达,Western blot鉴定,亲和层析纯化后分析重组蛋白的血凝效价及稳定性。结果：四种HA重组蛋白均获得有效表达,其中HA胞外区全长融合三聚化基序的重组蛋白（HA-T）表达水平最高,经Strep tag亲和层析获得高度纯化,产量高达30 mg/L,Ethylene glycolbis交联分析显示为稳定的HA三聚体形式,血凝活性分析显示HA-T的活性最高,血凝效价为29,动态光散射显示HA-T在4℃放置3个月性质稳定。结论：HA-T表达量高、稳定性好、血凝活性高且易于纯化,研究结果为流感重组蛋白疫苗的研发策略提供了参考。     

Histidine acts as a co‐germinant with glycine and taurocholate for Clostridium difficile spores

Aims: It is well established that the bile salt sodium taurocholate acts as a germinant for Clostridium difficile spores and the amino acid glycine acts as a co‐germinant. The aim of this study was to determine whether any other amino acids act as co‐germinants. Methods and Results: Clostridium difficile spore suspensions were exposed to different germinant solutions comprising taurocholate, glycine and an additional amino acid for 1 h before heating shocking (to kill germinating cells) or chilling on ice. Samples were then re‐germinated and cultured to recover remaining viable cells. Only five amino acids out of the 19 common amino acids tested (valine, aspartic acid, arginine, histidine and serine) demonstrated co‐germination activity with taurocholate and glycine. Of these, only histidine produced high levels of germination (97·9–99·9%) consistently in four strains of Cl. difficile spores. Some variation in the level of germination produced was observed between different PCR ribotypes, and the optimum concentration of amino acids with taurocholate for the germination of Cl. difficile NCTC 11204 spores was 10–100 mmol l^?1. Conclusions: Histidine was found to be a co‐germinant for Cl. difficile spores when combined with glycine and taurocholate. Significance and Impact of the Study: The findings of this study enhance current knowledge regarding agents required for germination of Cl. difficile spores which may be utilized in the development of novel applications to prevent the spread of Cl. difficile infection.