Interfacial Engineering of Polymer Membranes with Intrinsic Microporosity for Dendrite-free Zinc Metal Batteries.

Metallic zinc has emerged as a promising anode material for high-energy battery systems due to its high theoretical capacity (820 mA h g-1), low redox potential for two-electron reactions, cost-effectiveness and inherent safety. However, current zinc metal batteries face challenges in low coulombic efficiency and limited longevity due to uncontrollable dendrite growth, the corrosive hydrogen evolution reaction (HER) and decomposition of the aqueous ZnSO4 electrolyte. Here, we report an interfacial-engineering approach to mitigate dendrite growth and reduce corrosive reactions through the design of ultrathin selective membranes coated on the zinc anodes. The submicron-thick membranes derived from polymers of intrinsic microporosity (PIMs), featuring pores with tunable interconnectivity, facilitate regulated transport of Zn2+-ions, thereby promoting a uniform plating/stripping process. Benefiting from the protection by PIM membranes, zinc symmetric cells deliver a stable cycling performance over 1500 h at 1 mA/cm² with a capacity of 0.5 mAh while full cells with NaMnO2 cathode operate stably at 1 A g-1 over 300 cycles without capacity decay. Our work represents a new strategy of preparing multi-functional membranes that can advance the development of safe and stable zinc metal batteries.

Inhibition of Vanadium Cathodes Dissolution in Aqueous Zn-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) have experienced a rapid surge in popularity, as evident from the extensive research with over 30 000 articles published in the past 5 years. Previous studies on AZIBs have showcased impressive long-cycle stability at high current densities, achieving thousands or tens of thousands of cycles. However, the practical stability of AZIBs at low current densities (<1C) is restricted to merely 50-100 cycles due to intensified cathode dissolution. This genuine limitation poses a considerable challenge to their transition from the laboratory to the industry. In this study, leveraging density functional theory (DFT) calculations, an artificial interphase that achieves both hydrophobicity and restriction of the outward penetration of dissolved vanadium cations, thereby shifting the reaction equilibrium and suppressing the vanadium dissolution following Le Chatelier's principle, is described. The approach has resulted in one of the best cycling stabilities to date, with no noticeable capacity fading after more than 200 cycles (≈720 h) at 200 mA g-1 (0.47C). These findings represent a significant advance in the design of ultrastable cathodes for aqueous batteries and accelerate the industrialization of aqueous zinc-ion batteries.

Bio-Inspired Polyanionic Electrolytes for Highly Stable Zinc-Ion Batteries.

For zinc-ion batteries (ZIBs), the non-uniform Zn plating/stripping results in a high polarization and low Coulombic efficiency (CE), hindering the large-scale application of ZIBs. Here, inspired by biomass seaweed plants, an anionic polyelectrolyte alginate acid (SA) was used to initiate the in situ formation of the high-performance solid electrolyte interphase (SEI) layer on the Zn anode. Attribute to the anionic groups of -COO- , the affinity of Zn2+ ions to alginate acid induces a well-aligned accelerating channel for uniform plating. This SEI regulates the desolvation structure of Zn2+ and facilitates the formation of compact Zn (002) crystal planes. Even under high depth of discharge conditions (DOD), the SA-coated Zn anode still maintains a stable Zn stripping/plating behavior with a low potential difference (0.114 V). According to the classical nucleation theory, the nucleation energy for SA-coated Zn is 97 % less than that of bare Zn, resulting in a faster nucleation rate. The Zn||Cu cell assembled with the SA-coated electrode exhibits an outstanding average CE of 99.8 % over 1,400 cycles. The design is successfully demonstrated in pouch cells, where the SA-coated Zn exhibits capacity retention of 96.9 % compared to 59.1 % for bare Zn anode, even under the high cathode mass loading (>10 mg/cm2 ).

When It's Heavier: Interfacial and Solvation Chemistry of Isotopes in Aqueous Electrolytes for Zn-ion Batteries.

The electrochemical effect of isotope (EEI) of water is introduced in the Zn-ion batteries (ZIBs) electrolyte to deal with the challenge of severe side reactions and massive gas production. Due to the low diffusion and strong coordination of ions in D2 O, the possibility of side reactions is decreased, resulting in a broader electrochemically stable potential window, less pH change, and less zinc hydroxide sulfate (ZHS) generation during cycling. Moreover, we demonstrate that D2 O eliminates the different ZHS phases generated by the change of bound water during cycling because of the consistently low local ion and molecule concentration, resulting in a stable interface between the electrode and electrolyte. The full cells with D2 O-based electrolyte demonstrated more stable cycling performance which displayed ∼100 % reversible efficiencies after 1,000 cycles with a wide voltage window of 0.8-2.0 V and 3,000 cycles with a normal voltage window of 0.8-1.9 V at a current density of 2 A g-1 .

Sex differences in personality disorders in a Chinese clinical population.

Introduction: Sex differences in the frequency and severity of personality disorders (PDs) have been widely reported in Western countries. However, limited literature suggests a similar sex distribution in the Chinese clinical population. This study investigated sex differences in self-reported and interviewed patients with PDs in a clinical population in China. Materials and methods: The participants were 1,389 consecutive outpatients with a mean age of 30.5 years, including 634 (45.6%) males and 755 (54.4%) females. Self-reported PD traits were assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+). PDs were diagnosed according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis II (SCID-II). Results: Male outpatients reported more paranoid, schizotypal, antisocial, and passive-aggressive PD traits, whereas females reported more borderline PD traits on the PDQ-4+. Self-reported PD traits in male outpatients were more likely to reach the positive threshold of antisocial PD than in females (χ2 = 5.293, p = 0.021). Males were more likely to meet the criteria for schizoid (χ2 = 5.050, p = 0.025), narcissistic (χ2 = 27.244, p < 0.001), antisocial (χ2 = 11.430, p = 0.001), avoidant (χ2 = 5.098, p = 0.024), and obsessive-compulsive PD (χ2 = 5.496, p = 0.019) diagnoses in the SCID-II. In contrast, females were more likely to meet the criteria of histrionic (χ2 = 12.327, p = 0.001), borderline (χ2 = 28.538, p < 0.001), and dependent (χ2 = 4.919, p = 0.027) diagnoses. Discussion: These findings indicate gender differences in the traits, frequency, and pattern of PDs when assessed in a Chinese clinical population.

Protein expression-based classification of gastric cancer by immunohistochemistry of tissue microarray.

Recently, the Cancer Genome Atlas and Asian Cancer Research Group propose two new classifications system of gastric cancer by using multi-platforms of molecular analyses. However, these highly complicated and cost technologies have not yet been translated into full clinical utility. In addition, the clinicians are expected to gain more guidance of treatment for different molecular subtypes. In this study, we developed a panel of gastric cancer patients in population from Southern China using commercially accessible TMA and immunohistochemical technology. A cohort of 259 GC patients was classified into 4 subtypes on the basis of expression of mismatch repair proteins (PMS2, MLH1, MSH2, and MSH6), E-cadherin and p21 protein. We observed that the subtypes presented distinct prognosis. dMMR-like subtype was associated with the best prognosis, and E-cadherin-a subtype was associated with the worst prognosis. Patients with p21-High and p21-Ligh subtypes had intermediate overall survival. In multivariate analysis, the dMMR-like subtype remained an independent prediction power for overall survival in the model. We described a molecular classification of gastric cancers using clinically applicable assay. The biological relevance of the four subtypes was illustrated by significant differences in prognosis. Our molecular classification provided an effective and inexpensive screening tool for improving prognostic models. Nevertheless, our study should be considered preliminary and carries a limited predictive value as a single-center retrospective study.

Discovery of Macrocyclic Inhibitors of Apurinic/Apyrimidinic Endonuclease 1.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential base excision repair enzyme that is upregulated in a number of cancers, contributes to resistance of tumors treated with DNA-alkylating or -oxidizing agents, and has recently been identified as an important therapeutic target. In this work, we identified hot spots for binding of small organic molecules experimentally in high resolution crystal structures of APE1 and computationally through the use of FTMAP analysis ( http://ftmap.bu.edu/ ). Guided by these hot spots, a library of drug-like macrocycles was docked and then screened for inhibition of APE1 endonuclease activity. In an iterative process, hot-spot-guided docking, characterization of inhibition of APE1 endonuclease, and cytotoxicity of cancer cells were used to design next generation macrocycles. To assess target selectivity in cells, selected macrocycles were analyzed for modulation of DNA damage. Taken together, our studies suggest that macrocycles represent a promising class of compounds for inhibition of APE1 in cancer cells.

Evidence for existence of quorum sensing in a bioaugmented system by acylated homoserine lactone-dependent quorum quenching.

The introduction of a gene, strain, or microbial consortium into an indigenous bacterial population is known as bioaugmentation. This technique has been proposed as an effective strategy for accelerating and enhancing the removal of recalcitrant and toxic compounds during wastewater treatment. In this study, three types of reactors were used to test whether quorum sensing plays an important role in bioaugmented systems. Reverse transcriptase polymerase chain reaction showed that the inoculated strain, HF-1, successfully colonized in the bioaugmented reactor. Meanwhile, no HF-1 colonization was observed in the quorum-quenching and non-bioaugmented reactors. Removal of nicotine in the bioaugmented reactor was almost 100%, and removal of total organic carbon (TOC) was higher than 50%. However, less than 20% of nicotine and 30% of TOC was removed in quorum-quenching and non-bioaugmented reactors. Moreover, the release of acylated homoserine lactones reached the threshold for HF-1 biofilm formation in bioaugmented reactors but not in quorum-quenching or non-bioaugmented reactors. The addition of porcine kidney acylase I, a quenching reagent, to the quorum-quenching reactor hampered the colonization of HF-1. Together, these results demonstrate that quorum sensing plays an important role in HF-1 colonization of bioaugmented systems.

High-resolution crystal structures reveal plasticity in the metal binding site of apurinic/apyrimidinic endonuclease I.

Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg²âº-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg²âº, Mn²âº, and apo-APE1 determined at 1.4, 2.2, and 1.65 Å, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn²âº ion was observed coordinated by D70 and E96; the Mg²âº site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg²âº or Mn²âº to APE1. Consistent with the disorder exhibited by Mg²âº bound to the active site, two different conformations of E96 were observed coordinated to Mg²âº. A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²âº complex structure. Thus, binding of Mg²âº in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg²âº facilitated by the structural plasticity of E96 in the active site.

A new method for rapid construction of a Pseudomonas sp. HF-1 bioaugmented system: accelerating acylated homoserine lactones secretion by pH regulation.

Pseudomonas sp. HF-1 bioaugmented systems were operated to treat tobacco wastewater under pH 5.5 for three cycles and pH 8.0 for the rest, which was suitable for HF-1 biofilm formation. The results showed that, under pH control, the contents of 3-oxo-C6-HSL, C6-HSL and 3-oxo-C8-HSL were significantly higher than HF-1 thresholds for biofilm formation. Compared with non-pH controlled reactors, HF-1 showed greater colonization in pH controlled reactors, primarily owing to the high extracellular polymeric substances secretion induced by quorum sensing. Accordingly, high indigenous community activity and granular sludge were observed. Sludge granulation occurred from the seventh cycle, and the average diameter was greater than 400 µm. These systems were also highly efficient with nearly 100% nicotine degradation and 60% total organic carbon removal. Overall, the results indicate that pH regulation is a new and feasible method for acceleration of releasing of auto-inducers, which is beneficial to construction of HF-1 bioaugmented systems.

Crystal structures of GCN2 protein kinase C-terminal domains suggest regulatory differences in yeast and mammals.

In response to amino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and initiation of gene reprogramming that facilitates adaptation to nutrient stress. GCN2 is a multidomain protein with key regulatory domains that directly monitor uncharged tRNAs which accumulate during nutrient limitation, leading to activation of this eIF2 kinase and translational control. A critical feature of regulation of this stress response kinase is its C-terminal domain (CTD). Here, we present high resolution crystal structures of murine and yeast CTDs, which guide a functional analysis of the mammalian GCN2. Despite low sequence identity, both yeast and mammalian CTDs share a core subunit structure and an unusual interdigitated dimeric form, albeit with significant differences. Disruption of the dimeric form of murine CTD led to loss of translational control by GCN2, suggesting that dimerization is critical for function as is true for yeast GCN2. However, although both CTDs bind single- and double-stranded RNA, murine GCN2 does not appear to stably associate with the ribosome, whereas yeast GCN2 does. This finding suggests that there are key regulatory differences between yeast and mammalian CTDs, which is consistent with structural differences.

Effect of Pseudomonas sp. HF-1 inoculum on construction of a bioaugmented system for tobacco wastewater treatment: analysis from quorum sensing.

To better construct a bioaugmented system for tobacco wastewater treatment, activated sludge was inoculated with different concentrations of the nicotine-degrading bacterium Pseudomonas sp. HF-1. The results showed that inoculum concentrations of 0.55 ± 0.01 and 1.10 ± 0.03 mg/g (dry weight of strain HF-1/dry weight of activated sludge) were best to ensure strain HF-1 survival and successful bioaugmentation. The release pattern of autoinducer (AI) for quorum sensing in the bioaugmented system was also investigated. During the period of HF-1 inoculation, compared with failed bioaugmented systems, AI-2 was significantly increased in the successful systems, suggesting that AI-2-mediated bacterial communication played an important role in the colonization of HF-1. When inoculation of strain HF-1 was stopped, the amount of AI-2 decreased and leveled out in all systems. Notably, there was a greater than threefold increase of short-chain AHLs in failed bioaugmented systems, but no increase in successful ones, implying that the fluctuation of short-chain AHLs could be an indicator of the failure of bioaugmentation. Thus, AI-2-mediated quorum sensing could be implemented to facilitate HF-1 colonization.

Where are signal molecules likely to be located in anaerobic granular sludge?

Quorum sensing is a concentration-sensing mechanism that plays a vital role in sludge granulation. In this study, the regularities of distribution of different signal molecules, including intra- and interspecific signal molecules (diffusible signal factor, DSF), interspecific signal molecules (autoinducter-2, AI-2) and intraspecific signal molecules (acyl-homoserine lactones, AHLs), from three types of anaerobic granular sludge were investigated. The results showed that 70-90% of DSF was distributed in sludge, while AI-2 in the Water phase accounted for over 80% of the total content. Interestingly, there was a positive correlation between DSF and AI-2, which played opposite roles in granulation. Moreover, more than 55% of short and medium acyl chain AHLs tended to spread in aqueous water, while the long acyl chain AHLs were closer to granular sludge than the short and medium acyl chain AHLs. With the exception of one type of sludge, the percentage of long acyl chain AHLs in the sludge phase was greater than 70%. The different distributions of signal molecules were primarily determined based on their physicochemical properties, including molecular weight and solubility in water or organic solutions. In addition, the basic properties of sludge, such as the granular level or the production of EPS, were closely related to the diversity, distribution and concentration of signal molecules. As a medium in granulation, extracellular polymeric substances production was regulated by different signal molecules from different parts of anaerobic granular sludge. This study provides a foundation for investigation of quorum sensing in the system of anaerobic granular sludge.

Bioaugmentation of activated sludge with Acinetobacter sp. TW enhances nicotine degradation in a synthetic tobacco wastewater treatment system.

Bioaugmentation (BA) using Acinetobacter sp. TW with high nicotine-degrading efficiency was applied in a bioreactor receiving a load of COD (3,200 ± 50 mg/L) and nicotine (1.0 ± 0.1g/L). The results showed that because of the colonization of strain TW, the COD removal was stable at 80-90%, while nicotine removal reached 98% in the BA system. Furthermore, according to PCR-DGGE fingerprinting, compared with the originally activated sludge, more bacteria existed in the BA systems while some bacteria disappeared from the non-BA system. In terms of the quorum sensing, short chain AHLs increased to assist colonization of strain TW, and long chain AHLs were secreted and helped to resist the nicotine toxicity. Compared with the non-BA system, the amounts of ROS, protein carbonyls and 8-OHdG were significant lower in the BA systems, which suggested that strain TW played an important role in eliminating the nicotine toxicity from the bioreactors.

Ecological roles and release patterns of acylated homoserine lactones in Pseudomonas sp. HF-1 and their implications in bacterial bioaugmentation.

To enable development of a better bacterial bioaugmentation system for tobacco wastewater treatment, the roles and release patterns of acylated homoserine lactones (AHLs) in Pseudomonas sp. HF-1 were evaluated. Swarming was found to be induced by N-hexanoyl-homoserine lactone (C(6)-HSL) and N-3-oxo-hexanoyl-homoserine lactone (3-oxo-C(6)-HSL); the formation of extracellular polymeric substances (EPS) was induced by 3-oxo-C(6)-HSL, C(6)-HSL and N-3-oxo-octanoyl-homoserine lactone (3-oxo-C(8)-HSL); and biofilm formation was induced by C(6)-HSL and 3-oxo-C(8)-HSL. When the culture conditions were 25°C, pH 5-6, 3% inoculum, 1.5 g L(-1) nicotine and 1% NaCl, the amount of AHLs released was sufficient for quorum sensing of swarming and EPS formation for strain HF-1, which was beneficial to the startup stage during bioaugmentation. When strain HF-1 was cultured at pH 8 in the presence of 1.2-1.8 g L(-1) of nicotine and 1% NaCl, the threshold for quorum sensing of biofilm formation was reached and the bioaugmentation system showed an efficient performance.

The Gal3p transducer of the GAL regulon interacts with the Gal80p repressor in its ligand-induced closed conformation.

A wealth of genetic information and some biochemical analysis have made the GAL regulon of the yeast Saccharomyces cerevisiae a classic model system for studying transcriptional activation in eukaryotes. Galactose induces this transcriptional switch, which is regulated by three proteins: the transcriptional activator Gal4p, bound to DNA; the repressor Gal80p; and the transducer Gal3p. We showed previously that NADP appears to act as a trigger to kick the repressor off the activator. Sustained activation involves a complex of the transducer Gal3p and Gal80p mediated by galactose and ATP. We solved the crystal structure of the complex of Gal3p-Gal80p with α-D-galactose and ATP to 2.1 Å resolution. The interaction between the proteins occurs only when Gal3p is in a "closed" state induced by ligand binding. The structure of the complex provides a rationale for the phenotypes of several well-known Gal80p and Gal3p mutants as well as the lack of galactokinase activity of Gal3p.

Characterization of the redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease.

Apurinic/apyrimidinic endonuclease (APE1) is an unusual nuclear redox factor in which the redox-active cysteines identified to date, C65 and C93, are surface inaccessible residues whose activities may be influenced by partial unfolding of APE1. To assess the role of the five remaining cysteines in APE1's redox activity, double-cysteine mutants were analyzed, excluding C65A, which is redox-inactive as a single mutant. C93A/C99A APE1 was found to be redox-inactive, whereas other double-cysteine mutants retained the same redox activity as that observed for C93A APE1. To determine whether these three cysteines, C65, C93, and C99, were sufficient for redox activity, all other cysteines were substituted with alanine, and this protein was shown to be fully redox-active. Mutants with impaired redox activity failed to stimulate cell proliferation, establishing an important role for APE1's redox activity in cell growth. Disulfide bond formation upon oxidation of APE1 was analyzed by proteolysis of the protein followed by mass spectrometry analysis. Within 5 min of exposure to hydrogen peroxide, a single disulfide bond formed between C65 and C138 followed by the formation of three additional disulfide bonds within 15 min; 10 total disulfide bonds formed within 1 h. A single mixed-disulfide bond involving C99 of APE1 was observed for the reaction of oxidized APE1 with thioredoxin (TRX). Disulfide-bonded APE1 or APE1-TRX species were further characterized by size exclusion chromatography and found to form large complexes. Taken together, our data suggest that APE1 is a unique redox factor with properties distinct from those of other redox factors.

Crystal structure of the human Hsmar1-derived transposase domain in the DNA repair enzyme Metnase.

Although the human genome is littered with sequences derived from the Hsmar1 transposon, the only intact Hsmar1 transposase gene exists within a chimeric SET-transposase fusion protein referred to as Metnase or SETMAR. Metnase retains many of the transposase activities including terminal inverted repeat (TIR) specific DNA-binding activity, DNA cleavage activity, albeit uncoupled from TIR-specific binding, and the ability to form a synaptic complex. However, Metnase has evolved as a DNA repair protein that is specifically involved in nonhomologous end joining. Here, we present two crystal structures of the transposase catalytic domain of Metnase revealing a dimeric enzyme with unusual active site plasticity that may be involved in modulating metal binding. We show through characterization of a dimerization mutant, F460K, that the dimeric form of the enzyme is required for its DNA cleavage, DNA-binding, and nonhomologous end joining activities. Of significance is the conservation of F460 along with residues that we propose may be involved in the modulation of metal binding in both the predicted ancestral Hsmar1 transposase sequence as well as in the modern enzyme. The Metnase transposase has been remarkably conserved through evolution; however, there is a clustering of substitutions located in alpha helices 4 and 5 within the putative DNA-binding site, consistent with loss of transposition specific DNA cleavage activity and acquisition of DNA repair specific cleavage activity.

Redox regulation of DNA repair: implications for human health and cancer therapeutic development.

Redox reactions are known to regulate many important cellular processes. In this review, we focus on the role of redox regulation in DNA repair both in direct regulation of specific DNA repair proteins as well as indirect transcriptional regulation. A key player in the redox regulation of DNA repair is the base excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in its role as a redox factor. APE1 is reduced by the general redox factor thioredoxin, and in turn reduces several important transcription factors that regulate expression of DNA repair proteins. Finally, we consider the potential for chemotherapeutic development through the modulation of APE1's redox activity and its impact on DNA repair.

Discovery of inhibitors of Escherichia coli methionine aminopeptidase with the Fe(II)-form selectivity and antibacterial activity.

Methionine aminopeptidase (MetAP) is a promising target to develop novel antibiotics, because all bacteria express MetAP from a single gene that carries out the essential function of removing N-terminal methionine from nascent proteins. Divalent metal ions play a critical role in the catalysis, and there is an urgent need to define the actual metal used by MetAP in bacterial cells. By high throughput screening, we identified a novel class of catechol-containing MetAP inhibitors that display selectivity for the Fe(II)-form of MetAP. X-ray structure revealed that the inhibitor binds to MetAP at the active site with the catechol coordinating to the metal ions. Importantly, some of the inhibitors showed antibacterial activity at low micromolar concentration on Gram-positive and Gram-negative bacteria. Our data indicate that Fe(II) is the likely metal used by MetAP in the cellular environment, and MetAP inhibitors need to inhibit this metalloform of MetAP effectively to be therapeutically useful.