Confinement of ZIF-67-derived N, Co-doped C@Si on a 2D MXene for enhanced lithium storage.

A heterostructure composed of ZIF-67-derived nitrogen and cobalt-doped carbon enfolded silicon (C@Si) nanoparticles anchored on 2D MXene layers was constructed for boosting the performance of lithium-ion batteries (LIBs). The heterostructure anode demonstrated a high initial discharge capacity of 3021 mA h g-1 at 0.2 A g-1, retaining outstanding cycling stability with a reversible capacity of 520 mA h g-1 at 2000 mA g-1, and the coulombic efficiency remained above 97% after 500 cycles. The introduced Ti3C2 nanosheets and the cobalt-doped carbon can not only contribute to the interfacial transfer of Li+ and electrons but also buffer the volume expansion of Si.

One-Pot Hydrothermal-Derived rGO/MXene/Sulfur Composite Aerogels as Free-Standing Cathodes in Lithium-Sulfur Batteries.

The confinement and high utilization of sulfur in the cathodes is critical for improved cycling performance of lithium-sulfur batteries. In this case one-pot hydrothermal strategy is developed to produce rGO/MXene/sulfur composite aerogels where sulfur is in situ trapped in the 3D rGO/MXene conductive skeleton. The optimized composite aerogels as free-standing cathodes delivery a specific capacity of 951 mAhg-1 after 100 cycles at 0.2 C with a low fading rate of 0.062% per cycle. The excellent cycling performance is correlated with highly oxidized MXene and in situ formed sulfate/thiosulfate complex layer in the long-term cycles.

Enhanced uranium separation by charge enabling γ-MnO2 with oxygen vacancies.

Numerous efforts have been devoted to understanding the electron transfer process of uranium (UO22+) on adsorbent materials, whereas the potential oxygen vacancies (OVs) in metal oxides have long been overlooked. Once these interactions are taken into account, the emerging molecular orbital effects undoubtedly affect the adsorption process. Here, we synthesized CC/γ-MnO2 by growing MnO2 on carbon cloth (CC), followed by the creation of oxygen vacancies (OVs) through electrochemical methods to form CC/γ-MnO2-OVs. The CC/γ-MnO2-OVs shows significantly enhanced selectivity and durability for UO22+, with the maximum adsorption capacity increasing from 456.8 to 1648.1 mg/g (by a factor of 3.6). Theoretical calculations suggest that the generation of OVs leads to an increase in charge transfer and a decrease in adsorption energy between UO22+ and CC/γ-MnO2, due to the interaction between Mn 3d orbital in CC/γ-MnO2 and O 2p orbital in UO22+. The OVs in CC/γ-MnO2 provide a spatial structure for anchoring the OU=O moiety of UO22+, while the surface van der Waals forces and the formation of chemical bonds between Mn-U contribute to charge interactions. This synergistic effect allows CC/γ-MnO2-OVs to exhibit favorable selectivity, a large adsorption capacity, and rapid adsorption kinetics towards uranyl ions. This work achieves enhanced UO22+ separation by introducing OVs in CC/γ-MnO2 through a facile electrochemical strategy, highlighting the great potential for nuclear waste processing.

Highly Efficient Organic Dyes Capture Using Thiol-Functionalized Porous Organic Polymer.

It is of great significance to develop new materials for efficient capture cationic dyes methylene blue (MB) and malachite green (MG). In this work, a novel triptycene-based porous organic polymer with abundant thiol groups (TPP-SH) was prepared successfully by postmodification with a high surface area and robust triptycene-based porous organic polymer (TPP). The obtained TPP-SH exhibited a high surface area, good porosity, and good thermal stability. In addition, TPP-SH was highly effective at capturing MB and MG from aqueous solution because of the abundant thiols in its hierarchical structure. Under optimal adsorption conditions, the maximum adsorption capacities of MB and MG calculated by the Langmuir model at room temperature were 1146.3 and 689.6 mg g-1, respectively. These values are higher than those of many reported materials. The MB and MG adsorption rates were 0.0154 and 6.69 × 10-4 mg g-1 min-1, respectively. Furthermore, the polymer TPP-SH had a good recycling performance after adsorption-desorption at least five times. Therefore, the TPP-SH exhibited a high adsorption capacity, fast adsorption kinetics, and easy-recycling behavior, providing a new avenue for the preparation of green functionalized adsorbents with good performance for water decontamination.

Efficient adsorption of methyl orange and methyl blue dyes by a novel triptycene-based hyper-crosslinked porous polymer.

It is still a great challenge to develop new materials for the highly efficient entrapment of organic dyes from aqueous solution. Herein, a novel triptycene-based hyper-crosslinked porous polymer (TPP-PP) was designed and synthesized by a simple Friedel-Crafts reaction. The obtained polymer TPP-PP has a high surface area, abundant pore structure and stable thermal performance. Due to the above characteristics, TPP-PP has good adsorption performance for anionic methyl orange solution (MO) and cationic methyl blue solution (MB). Under the optimal experiment conditions, the TPP-PP showed an excellent adsorption capacity for MO (220.82 mg g-1) and MB (159.80 mg g-1), respectively. The adsorption kinetics fitted the pseudo-second-order model. The adsorption of MO by TPP-PP reaches equilibrium within 180 minutes, and the adsorption of MB reaches equilibrium within 150 minutes. The adsorption behavior was not only spontaneous but also endothermic in reality. At the same time, TPP-PP also has good reusability. After 5 cycles of experiments, the removal rate of MO and MB by TPP-PP can still reach more than 80%. Thus, the Friedel-Crafts reaction crosslinked method might be a promising approach for the synthesis of novel material for the highly efficient extraction of dye wastewater.

Discerning Tyrosine Phosphorylation from Multiple Phosphorylations Using a Nanofluidic Logic Platform.

Discerning tyrosine phosphorylation (pTyr) catalyzed by Tyr kinase is central to the revelation of oncogenic mechanisms and the development of targeted anticancer drugs. Despite some techniques, this goal remains challenging, especially when faced with the interference of multiple phosphorylation events, including serine (pSer) and threonine phosphorylation (pThr). We describe here a functional polymer-modified artificial ion nanochannel, which enables the sensitive and selective recognition of phosphotyrosine (pY) peptide by the distinct ionic current change. Such a recognition effect allows for the nanochannel to work in a complex protein digest condition. Further, the implementation of nanofluidic logic functions with the addition of Ca2+ dramatically improves the selectivity of the nanochannel to pY peptide and thus can discern pTyr by the Tyr kinase from pSer by the Ser/Thr kinase through simultaneously monitoring multisite phosphorylation at the same or different peptide substrates in one-pot. This logic sensing platform displays the potential in differentiating Tyr kinase and Ser/Thr kinase and assessing multi-kinase activities in multi-targeted drug design.

Benzothiazolyl and Benzoxazolyl Hydrazones Function as Zinc Metallochaperones to Reactivate Mutant p53.

We identified a set of thiosemicarbazone (TSC) metal ion chelators that reactivate specific zinc-deficient p53 mutants using a mechanism called zinc metallochaperones (ZMCs) that restore zinc binding by shuttling zinc into cells. We defined biophysical and cellular assays necessary for structure-activity relationship studies using this mechanism. We investigated an alternative class of zinc scaffolds that differ from TSCs by substitution of the thiocarbamoyl moiety with benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones. Members of this series bound zinc with similar affinity and functioned to reactivate mutant p53 comparable to the TSCs. Acute toxicity and efficacy assays in rodents demonstrated C1 to be significantly less toxic than the TSCs while demonstrating equivalent growth inhibition. We identified C85 as a ZMC with diminished copper binding that functions as a chemotherapy and radiation sensitizer. We conclude that the benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones can function as ZMCs to reactivate mutant p53 in vitro and in vivo.

Functional Nanochannels for Sensing Tyrosine Phosphorylation.

Tyrosine phosphorylation (pTyr), much of which occurred on localized multiple sites, initiates cellular signaling, governs cellular functions, and its dysregulation is implicated in many diseases, especially cancers. pTyr-specific sensing is of great significance for understanding disease states and developing targeted anticancer drugs, however, it is very challenging due to the slight difference from serine (pSer) or threonine phosphorylation (pThr). Here we present polyethylenimine-g-phenylguanidine (PEI-PG)-modified nanochannels that can address the challenge. Rich guanidinium groups enabled PEI-PG to form multiple interactions with phosphorylated residues, especially pTyr residue, which triggered the conformational change of PEI-PG. By taking advantage of the "OFF-ON" change of the ion flux arising from the conformational shrinkage of the grafted PEI-PG, the nanochannels could distinguish phosphorylated peptide (PP) from nonmodified peptide, recognize PPs with pSer, pThr, or pTyr residue and PPs with different numbers of identical residues, and importantly could sense pTyr peptides in a biosample. Benefiting from the strong interaction between the guanidinium group and the pTyr side-chain, the specific sensing of pTyr peptide was achieved by performing a simple logic operation based on PEI-PG-modified nanochannels when Ca2+ was introduced as an interferent. The excellent pTyr sensing capacity makes the nanochannels available for real-time monitoring of the pTyr process by c-Abl kinase on a peptide substrate, even under complicated conditions, and the proof-of-concept study of monitoring the kinase activity demonstrates its potential in kinase inhibitor screening.

Combinatorial Therapy of Zinc Metallochaperones with Mutant p53 Reactivation and Diminished Copper Binding.

Chemotherapy and radiation are more effective in wild-type (WT) p53 tumors due to p53 activation. This is one rationale for developing drugs that reactivate mutant p53 to synergize with chemotherapy and radiation. Zinc metallochaperones (ZMC) are a new class of mutant p53 reactivators that restore WT structure and function to zinc-deficient p53 mutants. We hypothesized that the thiosemicarbazone, ZMC1, would synergize with chemotherapy and radiation. Surprisingly, this was not found. We explored the mechanism of this and found the reactive oxygen species (ROS) activity of ZMC1 negates the signal on p53 that is generated with chemotherapy and radiation. We hypothesized that a zinc scaffold generating less ROS would synergize with chemotherapy and radiation. The ROS effect of ZMC1 is generated by its chelation of redox active copper. ZMC1 copper binding (K Cu) studies reveal its affinity for copper is approximately 108 greater than Zn2+ We identified an alternative zinc scaffold (nitrilotriacetic acid) and synthesized derivatives to improve cell permeability. These compounds bind zinc in the same range as ZMC1 but bound copper much less avidly (106- to 107-fold lower) and induced less ROS. These compounds were synergistic with chemotherapy and radiation by inducing p53 signaling events on mutant p53. We explored other combinations with ZMC1 based on its mechanism of action and demonstrate that ZMC1 is synergistic with MDM2 antagonists, BCL2 antagonists, and molecules that deplete cellular reducing agents. We have identified an optimal Cu2+:Zn2+ binding ratio to facilitate development of ZMCs as chemotherapy and radiation sensitizers. Although ZMC1 is not synergistic with chemotherapy and radiation, it is synergistic with a number of other targeted agents.

Therapeutic targeting of BRCA1 and TP53 mutant breast cancer through mutant p53 reactivation.

Triple negative breast cancer (TNBC) is an aggressive subset for which effective therapeutic approaches are needed. A significant proportion of TNBC patients harbor either germline or somatic mutations in BRCA1, or epigenetic silencing of BRCA1, which renders them deficient in DNA repair. Virtually all BRCA1 deficient breast cancers harbor mutations in TP53 suggesting that inactivation of p53 is a requirement for tumor progression in the setting of BRCA1 deficiency. Due to this dependency, we hypothesized that restoring wild type p53 function in BRCA1 deficient breast cancer would be therapeutic. The majority of TP53 mutations are missense, which generate a defective protein that potentially can be targeted with small molecules. Zinc metallochaperones (ZMCs) are a new class of anti-cancer drugs that specifically reactivate zinc-deficient mutant p53 by restoring zinc binding. Using ZMC1 in human breast cancer cell lines expressing the zinc deficient p53R175H, we demonstrate that loss of BRCA1 sensitizes cells to mutant p53 reactivation. Using murine breast cancer models with Brca1 deficiency, we demonstrate that ZMC1 significantly improves survival of mice bearing tumors harboring the zinc-deficient Trp53 R172H allele but not the Trp53 -/- allele. We synthesized a new formulation of ZMC1 (Zn-1), in which the drug is made in complex with zinc to improve zinc delivery, and demonstrate that Zn-1 has increased efficacy. Furthermore, we show that ZMC1 plus olaparib is a highly effective combination for p53R172H tumor growth inhibition. In conclusion, we have validated preclinically a new therapeutic approach for BRCA1 deficient breast cancer through reactivation of mutant p53.

Biomimetic nanochannels for the discrimination of sialylated glycans via a tug-of-war between glycan binding and polymer shrinkage.

Sialylated glycans that are attached to cell surface mediate diverse cellular processes such as immune responses, pathogen binding, and cancer progression. Precise determination of sialylated glycans, particularly their linkage isomers that can trigger distinct biological events and are indicative of different cancer types, remains a challenge, due to their complicated composition and limited structural differences. Here, we present a biomimetic nanochannels system integrated with the responsive polymer polyethyleneimine-g-glucopyranoside (Glc-PEI) to solve this problem. By using a dramatic "OFF-ON" change in ion flux, the nanochannels system achieves specific recognition for N-acetylneuraminic acid (Neu5Ac, the predominant form of sialic acid) from various monosaccharides and sialic acid species. Importantly, different "OFF-ON" ratios of the conical nanochannels system allows the precise and sensitive discrimination of sialylated glycan linkage isomers, α2-3 and α2-6 linkage (the corresponding ion conductance increase ratios are 96.2% and 264%, respectively). Analyses revealed an unusual tug-of-war mechanism between polymer-glycan binding and polymer shrinkage. The low binding affinity of Glc-PEI for the α2-6-linked glycan caused considerable shrinkage of Glc-PEI layer, but the high affinity for the α2-3-linked glycan resulted in only a slight shrinkage. This competition mechanism provides a simple and versatile materials design principle for recognition or sensing systems that involve negatively charged target biomolecules. Furthermore, this work broadens the application of nanochannel systems in bioanalysis and biosensing, and opens a new route to glycan analysis that could help to uncover the mysterious and wonderful glycoworld.

Effect of thermal treatment of Pd decorated Fe/C nanocatalysts on their catalytic performance for formic acid oxidation.

The thermal treatment of bimetallic nanocatalysts plays an important role in determining their catalytic performance. Here tuning the surface oxidized metal species of bimetallic Pd-Fe electrocatalysts for the formic acid (FA) oxidation reaction is reported and a correlation between the surface oxidized metal species of the Pd-Fe nanoparticles and their catalytic activities is proposed. The structural details of the Pd-Fe/C catalysts are characterized by X-ray diffraction, X-ray photoelectron spectroscopy and high-sensitivity low-energy ion scattering (HS-LEIS). Cyclic voltammetry measurements demonstrated that the mass activity of the Pd-Fe nanoparticles with a molar ratio of Pd/Fe = 1/15 is about 7.4 times higher than that of Pd/C. This enhancement could be attributed to the synergistic effect between Pd(0) and Pd oxidized species on the surface of the Pd-Fe/C treated sample and electronic effects. This finding demonstrates the importance of surface oxidized metal species at the nanoscale in harnessing the true electrocatalytic potential of bimetallic nanoparticles and opens up strategies for the development of highly active bimetallic nanoparticles for electrochemical energy conversion.

Strong Confinement Effects on Homocrystallization by Stereocomplex Crystals in Electrospun Polylactide Fibers.

In asymmetric poly(l-lactide)/poly(d-lactide) (PLLA/PDLA) blends, the pre-existing stereocomplex crystals can impose confinement effects on homocrystallization of uncomplexed PLLA among them. However, confinement effects are very weak in the blend films because of relatively large PLLA domains distributed in the skeleton of stereocomplex crystals. As a comparison, in the electrospun blend fibers, fine distribution of uncomplexed PLLA results in strong confinement effects. This is manifested by the significant decrease in the crystallization temperature and melting point. Even so, confinement effects have little influence on the crystal form, and PLLA α-crystals prevail in the electrospun blend fibers after melt crystallization. Finally, confinement effects in the electrospun blend fibers depend on annealing temperatures and almost disappear when the samples are annealed above the melting point of stereocomplex crystals.

Critical Composition of the ß Form of Poly(vinylidene fluoride) in Miscible Crystalline/Crystalline Blends.

Crystallization and the polymorphic transition of poly(vinylidene fluoride) (PVDF) in its miscible blends with poly(butylene succinate) (PBS) from the melt has been investigated. The presence of a miscible PBS component lowers the crystallization temperature and the melting point of the PVDF component in the blends. It becomes more significant above a critical PBS content between 40 and 50 wt % where PVDF chains are dispersed in the matrix composed by PBS chains. On the other hand, the ß form of the PVDF component can be induced at low temperatures, which also has a transition at the critical PBS content.

Characterization of the minimal length of functional SecA in Escherichia coli.

Previous studies showed that certain regions of E. coli SecA can be deleted from its N- and/or C-termini to complement a SecA amber ts mutant. In this study, we determined and characterized the dispensability of both ends of SecA molecules. With N-terminal intact or 9-aa deleted, 826aa (SecA1-826 and SecA10-826, respectively) is the minimum for complementation activity, while with N-terminus deleted by 2-21aa, SecA22-829 is the minimum. Further deletion at the C-terminus of SecA1-826/SecA10-826/SecA22-829 abolished the complementation activity in the cells. A hydrophobic amino acid is required for the 826th residue in the minimal-length SecAs. Chemical crosslinking and gel filtration result showed that both purified SecA22-828 and SecA22-829 could form a dimer. Moreover, the in vitro ATPase and protein translocation activities of SecA22-828 and SecA22-829 were similar, though lower than wild-type SecA. The active mutants had more truncated SecA in soluble than membrane-bound form, but was more stably embedded in membranes. In contrast, the inactive mutants tended to have truncated SecA more membrane-bound than soluble form, and were more loosely bound and easily chased out. Thus, the loss of complementation appears to be related to their altered subcellular localization and stability in the membranes. This study defines the substantial regions of N- and C-termini of SecA that may be deleted without losing complementation activity.

A revolutionary road: an analysis of persons living with hepatitis B in China.

This study explores the interactions of the environmental barriers, coping behaviors, and personal characteristics of persons living with hepatitis B in China within the framework of Bandura's social cognitive theory. An analysis of 1,607 messages from an online support group revealed multiple barriers including institutional discrimination, relationship difficulty, alcohol-drinking social norm, limitations of the health care system and pharmaceutical market, and financial constraints. Major coping behaviors were identified as seeking health and reproductive advice, avoiding disclosure and discrimination, protecting legal rights, preventing transmission, and outreaching support behaviors. At the intrapersonal level, a combatant identity was constructed in the online community. The combatant identity was significantly associated with high self-efficacy, positive emotions, and outreaching support behaviors, but it was not significantly associated with environmental barriers. The constructed online combatant identity appeared to be support-focused instead of politically oriented.

Hepatitis B virus alters the antioxidant system in transgenic mice and sensitizes hepatocytes to Fas signaling.

Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the precise pathogenetic mechanisms linking HBV infection and HCC remain uncertain. It has been reported that decreased antioxidant enzyme activities are associated with severe liver injury and hepatocarcinogenesis in mouse models. It is unclear if HBV can interfere with the activities of antioxidant enzymes. We established a HBV transgenic mouse line, which spontaneously developed HCC at 2 years of age. We studied the activities of the antioxidant enzymes in the liver of the HBV transgenic mice. Our results showed that the antioxidant enzymes glutathione peroxidase and superoxide dismutase 2 were down-regulated in HBV transgenic mice and correlated with JNK activation. HBV enhanced the Fas-mediated activation of caspase 6, caspase 8 and JNK without enhancing the activation of caspase 3 and hepatocellular apoptosis. As a proper redox balance is important for maintaining cellular homeostasis, these effects of HBV on the host antioxidant system and Fas-signaling may play an important role in HBV-induced hepatocarcinogenesis.

Transgenic expression of entire hepatitis B virus in mice induces hepatocarcinogenesis independent of chronic liver injury.

Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV ("preS2 mutant") that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged--2-year-old--mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines--expressing either mutant or wildtype HBV--therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC.

SecA alone can promote protein translocation and ion channel activity: SecYEG increases efficiency and signal peptide specificity.

SecA is an essential component of the Sec-dependent protein translocation pathway across cytoplasmic membranes in bacteria. Escherichia coli SecA binds to cytoplasmic membranes at SecYEG high affinity sites and at phospholipid low affinity sites. It has been widely viewed that SecYEG functions as the essential protein-conducting channel through which precursors cross the membranes in bacterial Sec-dependent pathways, and that SecA functions as a motor to hydrolyze ATP in translocating precursors through SecYEG channels. We have now found that SecA alone can promote precursor translocation into phospholiposomes. Moreover, SecA-liposomes elicit ionic currents in Xenopus oocytes. Patch-clamp recordings further show that SecA alone promotes signal peptide- or precursor-dependent single channel activity. These activities were observed with the functional SecA at about 1-2 µM. The results show that SecA alone is sufficient to promote protein translocation into liposomes and to elicit ionic channel activity at the phospholipids low affinity binding sites, thus indicating that SecA is able to form the protein-conducting channels. Even so, such SecA-liposomes are less efficient than those with a full complement of Sec proteins, and lose the signal-peptide proofreading function, resembling the effects of PrlA mutations. Addition of purified SecYEG restores the signal peptide specificity and increases protein translocation and ion channel activities. These data show that SecA can promote protein translocation and ion channel activities both when it is bound to lipids at low affinity sites and when it is bound to SecYEG with high affinity. The latter of the two interactions confers high efficiency and specificity.

Unusual cold crystallization behavior in physically aged poly(L-lactide).

A comparative study of cold crystallization behavior in poly(L-lactide) (PLLA) annealed below and just above the glass transition temperature (T(g)) has been conducted. Annealing benefits the generation of local order and the subsequent cold crystallization process, which becomes significant in PLLA annealed just above T(g). Surprisingly, morphological observation reveals high density nuclei in PLLA annealed below T(g), contrary to its relatively slow crystallization kinetics. This unusual crystallization behavior in physically aged PLLA arises from the retarded crystal growth rate because of incomplete recovery of reduced segmental mobility above T(g). In contrast, annealing just above T(g) has little influence on the crystal growth rate, and the increased nucleation density alone accounts for the accelerated crystallization rate.