Pillaring Electronic Nano-Wires to Slice T-Nb2O5 Laminated Particles for Durable Lithium-Ion Batteries.

T-Nb2O5 characterized by the pronounced intercalation pseudocapacitance effect, is regarded as a promising and alternative anode for fast-charging Li-ion batteries. However, its electrochemical kinetics are still hindered by the absence of sufficient and homogenous conductive wiring inside active microparticles. Herein, an in situ pillaring strategy of electronic nano-wires is proposed to slice T-Nb2O5 laminated particles for the development of durable and fast-charging anodes for Li-ion batteries. A micro-level layered structure consisting of nano-carbon-inserted T-Nb2O5 composite flakes is designed and enabled by successive ion exchange, slice exfoliation, in situ polymerization, and carbonization processes. The pillared carbon interlayer (derived from polyaniline) can serve as in-built conductive wires to promote and homogenize electron transfer inside the micro-level particles. The porous structure (formed by the self-assembly of exfoliated flakes) contributes to the improved electrolyte immersion and enhanced lithium migration. Benefitting from the kinetically favorable effects, the modified T-Nb2O5 anode achieves the high-rate capability (108.4 mAh g-1 at 10 A g-1) and ultralong cycling durability (138 mAh g-1 at 1.0 A g-1 after 8000 cycles, with an average capacity decaying rate as small as 0.043‰). This work provides an effective strategy of electron wire pillaring with the slicing effect for laminated electrode materials with high tap density.

Dual photo-controlled release system for fipronil and dinotefuran.

Development of controlled release system promises a huge impact on the pesticide delivery, which has raised attentions in improving efficacy of pesticides. Herein, the emerging photoremovable protecting group (PRPG), used in spatiotemporal delivery of drug by light, was introduced into agriculture. We obtained three TNB-insecticides and two of them exhibited excellent photophysicochemical properties. Our dual photo-controlled release system displayed more than sixfold insecticidal activity differences upon irradiation with UV light or sunlight. The dual release of DIN-TNB-DIN showed synergistic effect on mosquito larvae and armyworm larvae. Distribution of the fluorescence in body of dead/alive wigglers clearly illustrated the action mode, and visually demonstrated the precise and spatiotemporal delivery of insecticides in the living mosquito larvae. The new developed dual photo-controlled release system might widen the diversity in pesticide delivery, promoting the development in improving pesticide efficacy.

Phagolysosome acidification is required for silica and engineered nanoparticle-induced lysosome membrane permeabilization and resultant NLRP3 inflammasome activity.

NLRP3 inflammasome activation occurs in response to hazardous particle exposures and is critical for the development of particle-induced lung disease. Mechanisms of Lysosome Membrane Permeabilization (LMP), a central pathway for activation of the NLRP3 inflammasome by inhaled particles, are not fully understood. We demonstrate that the lysosomal vATPases inhibitor Bafilomycin A1 blocked LMP in vitro and ex vivo in primary murine macrophages following exposure to silica, multi-walled carbon nanotubes, and titanium nanobelts. Bafilomycin A1 treatment of particle-exposed macrophages also resulted in decreased active cathepsin L in the cytosol, a surrogate measure for leaked cathepsin B, which was associated with less NLRP3 inflammasome activity. Silica-induced LMP was partially dependent upon lysosomal cathepsins B and L, whereas nanoparticle-induced LMP occurred independent of cathepsin activity. Furthermore, inhibition of lysosomal cathepsin activity with CA-074-Me decreased the release of High Mobility Group Box 1. Together, these data support the notion that lysosome acidification is a prerequisite for particle-induced LMP, and the resultant leak of lysosome cathepsins is a primary regulator of ongoing NLRP3 inflammasome activity and release of HMGB1.

Schiff base complexes of copper and zinc as potential anti-colitic compounds.

The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct. These compounds were tested in a formalin induced colonic inflammation model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff base analogue of sulfasalazine was designed. This was tested against a trinitrobenzenesulfonic acid (TNB) induced colitic model in Wistar rats. The use of two models allows us to test our compounds in both an acute and a chronic model. The trimodal compound reported is observed to provide anticolitic properties in the chronic TNB induced colitis model commensurate with that of SASP. However, the design of trimodal compound still has the capacity for further development. This the platform reported may offer a route into compounds which can markedly outperform the anti-colitic properties of SASP.

Quantification of thiols and disulfides.

BACKGROUND: Disulfide bond formation is a key posttranslational modification, with implications for structure, function and stability of numerous proteins. While disulfide bond formation is a necessary and essential process for many proteins, it is deleterious and disruptive for others. Cells go to great lengths to regulate thiol-disulfide bond homeostasis, typically with several, apparently redundant, systems working in parallel. Dissecting the extent of oxidation and reduction of disulfides is an ongoing challenge due, in part, to the facility of thiol/disulfide exchange reactions. SCOPE OF REVIEW: In the present account, we briefly survey the toolbox available to the experimentalist for the chemical determination of thiols and disulfides. We have chosen to focus on the key chemical aspects of current methodology, together with identifying potential difficulties inherent in their experimental implementation. MAJOR CONCLUSIONS: While many reagents have been described for the measurement and manipulation of the redox status of thiols and disulfides, a number of these methods remain underutilized. The ability to effectively quantify changes in redox conditions in living cells presents a continuing challenge. GENERAL SIGNIFICANCE: Many unresolved questions in the metabolic interconversion of thiols and disulfides remain. For example, while pool sizes of redox pairs and their intracellular distribution are being uncovered, very little is known about the flux in thiol-disulfide exchange pathways. New tools are needed to address this important aspect of cellular metabolism. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

The potentiation of myeloperoxidase activity by the glycosaminoglycan-dependent binding of myeloperoxidase to proteins of the extracellular matrix.

BACKGROUND: Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. METHODS: We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. RESULTS: MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. CONCLUSIONS: Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. GENERAL SIGNIFICANCE: Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

Application of TNB in dual photo-controlled release of phenamacril, imidacloprid, and imidacloprid synergist.

Pesticides can improve crops' yield and quality, but unreasonable applications of pesticides lead to waste of pesticides which are further accumulated in the environment and threaten human health. Developing the release of controlled drugs can improve the utilization rate of pesticides. Among these methods, light-controlled release is a new technology of controlled release, which can realize spatiotemporal delivery of drugs by light. Four compounds, named Imidacloprid-Thioacetal o-nitrobenzyl-Phenamacril (IMI-TNB-PHE), Imidacloprid-Thioacetal o-nitrobenzyl- Imidacloprid (IMI-TNB-IMI), Phenamacril-Thioacetal o-nitrobenzyl-Phenamacril (PHE-TNB-PHE), and Imidacloprid-Thioacetal o-nitrobenzyl-Imidacloprid Synergist (IMI-TNB-IMISYN), were designed and synthesized by connecting thioacetal o-nitrobenzyl (TNB) with pesticides TNB displaying simple and efficient optical properties in this work. Dual photo-controlled release of pesticides including two molecules of IMI or PHE, both IMI and PHE, as well as IMI and IMISYN were, respectively, studied in this paper. Insecticidal/fungicidal activities of the photosensitive pesticides showed 2-4 times increments if they were exposed to light. In addition, a synergistic effect was observed after the light-controlled release of IMI-TNB-IMISYN, which was consistent with the effect of IMISYN. The results demonstrated whether dual photo-controlled release of the same or different pesticide molecules could be achieved with a TNB linker with spatiotemporal precision. We envisioned that TNB will be an innovative photosensitive protective group for light-dependent application of agrochemicals in the future.

Extracellular organic disulfide reduction by Shewanella oneidensis MR-1.

Microbial reduction of organic disulfides affects the macromolecular structure and chemical reactivity of natural organic matter. Currently, the enzymatic pathways that mediate disulfide bond reduction in soil and sedimentary organic matter are poorly understood. In this study, we examined the extracellular reduction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) by Shewanella oneidensis strain MR-1. A transposon mutagenesis screen performed with S. oneidensis resulted in the isolation of a mutant that lost ~90% of its DTNB reduction activity. Genome sequencing of the mutant strain revealed that the transposon was inserted into the dsbD gene, which encodes for an oxidoreductase involved in cytochrome c maturation. Complementation of the mutant strain with the wild-type dsbD partially restored DTNB reduction activity. Because DsbD catalyzes a critical step in the assembly of multi-heme c-type cytochromes, we further investigated the role of extracellular electron transfer cytochromes in organic disulfide reduction. The results indicated that mutants lacking proteins in the Mtr system were severely impaired in their ability to reduce DTNB. These findings provide new insights into extracellular organic disulfide reduction and the enzymatic pathways of organic sulfur redox cycling.IMPORTANCEOrganic sulfur compounds in soils and sediments are held together by disulfide bonds. This study investigates how Shewanella oneidensis breaks apart extracellular organic sulfur compounds. The results show that an enzyme involved in the assembly of c-type cytochromes as well as proteins in the Mtr respiratory pathway is needed for S. oneidensis to transfer electrons from the cell surface to extracellular organic disulfides. These findings have important implications for understanding how organic sulfur decomposes in terrestrial ecosystems.

"I'm trying to take the lead from my child": experiences Parenting Young Nonbinary Children.

BACKGROUND: While research has emphasized the importance of parental support for LGBTQIA + youth wellbeing, there remains limited understanding of parental experiences with nonbinary children, particularly those prepubescent. This study aimed to explore how parents of nonbinary children ages 5-8 learn to support their child's identity, examining initial reactions, emotional processes, supportive behaviors, societal responses, and associated challenges and rewards. METHODS: A qualitative study was conducted using Reflexive Thematic Analysis (RTA) within a framework of ontological relativism and epistemological constructivism. Nine parents of nonbinary children aged 5-8 from the Northeastern United States participated in semi-structured interviews lasting 60-80 min. Questions explored various aspects of parenting nonbinary children, including the child's gender identity, parental feelings, experiences sharing the child's identity, and challenges and rewards of raising a gender-diverse child. The research team, comprising individuals who identify as trans, genderqueer, and nonbinary, employed collaborative coding and thematic development. RESULTS: Four main themes were constructed: (1) Parents hear and support their child's nonbinary identity, this theme highlights immediate acceptance and efforts parents make to affirm their child's gender; (2) Parents learn about ways cisnormative society harms their child, here, parents recognize the societal pressures and barriers their children face; (3) Parents take significant and proactive steps to affirm their child, this theme documents the actions parents take to support their child in environments that invalidate their identity; and (4) Gender is just one aspect of who my child is, this theme reflects on parental insights of gender as just one part of their child's overall personhood. CONCLUSIONS: This study provides insights into the experiences of parents supporting young nonbinary children, emphasizing the importance of affirming expressed identity, the parent-child relationship, and proactive support in navigating cisnormative societal structures. Findings highlight the transformative experience of parenting nonbinary children, with parents often challenging their own preconceptions of gender and coming to more nuanced understandings. These results can inform supportive interventions and policies for nonbinary children and their families, and we hope to contribute to a growing body of research that shifts narratives towards joy, resilience, and community in trans and nonbinary experiences.

Tuberal hypothalamic expression of the glial intermediate filaments, glial fibrillary acidic protein and vimentin across the turkey hen (Meleagris gallopavo) reproductive cycle: Further evidence for a role of glial structural plasticity in seasonal reproduction.

Glia regulate the hypothalamic-pituitary-gonadal (HPG) axis in birds and mammals. This is accomplished mechanically by ensheathing gonadotrophin-releasing hormone I (GnRH) nerve terminals thereby blocking access to the pituitary blood supply, or chemically in a paracrine manner. Such regulation requires appropriate spatial associations between glia and nerve terminals. Female turkeys (Meleagris gallopavo) use day length as a primary breeding cue. Long days activate the HPG-axis until the hen enters a photorefractory state when previously stimulatory day lengths no longer support HPG-axis activity. Hens must then be exposed to short days before reactivation of the reproductive axis occurs. As adult hens have discrete inactive reproductive states in addition to a fertile state, they are useful for examining the glial contribution to reproductive function. We immunostained tuberal hypothalami from short and long-day photosensitive hens, plus long-day photorefractory hens to examine expression of two intermediate filaments that affect glial morphology: glial fibrillary acidic protein (GFAP) and vimentin. GFAP expression was drastically reduced in the central median eminence of long day photosensitive hens, especially within the internal zone. Vimentin expression was similar among groups. However, vimentin-immunoreactive fibers abutting the portal vasculature were significantly negatively correlated with GFAP expression in the median eminence, which is consistent with our hypothesis for a reciprocal relationship between GFAP and vimentin expression. It appears that up-regulation of GFAP expression in the central median eminence of turkey hens is associated with periods of reproductive quiescence and that photofractoriness is associated with the lack of a glial cytoskeletal response to long days.

Graphite-Based Composite Anodes with C-O-Nb Heterointerfaces Enable Fast Lithium Storage.

To better satisfy the increasing demands for electric vehicles, it is crucial to develop fast-charging lithium-ion batteries (LIBs). However, the fast-charging capability of commercial graphite anodes is limited by the sluggish Li+ insertion kinetics. Herein, we report a synergistic engineering of uniform nano-sized T-Nb2 O5 particles on graphite (Gr@Nb2 O5 ) with C-O-Nb heterointerfaces, which prevents the growth and aggregation of T-Nb2 O5 nanoparticles. Through detailed theoretical calculations and pair distribution function analysis, the stable existence of the heterointerfaces is proved, which can accelerate the electron/ion transport. These heterointerfaces endow Gr@Nb2 O5 anodes with high ionic conductivity and excellent structural stability. Consequently, Gr@10-Nb2 O5 anode, where the mass ratio of T-Nb2 O5 /graphite=10/100, exhibits excellent cyclic stability and incredible rate capabilities, with 100.5 mAh g-1 after 10000 stable cycles at an ultrahigh rate of 20 C. In addition, the synergistic Li+ storage mechanism is revealed by systematic electrochemical characterizations and in situ X-ray diffraction. This work offers new insights to the reasonable design of fast-charging graphite-based anodes for the next generation of LIBs.

Change in Finances, Peer Access, and Mental Health Among Trans and Nonbinary People During the COVID-19 Pandemic.

Purpose: Due to structural transphobia, trans and nonbinary (TNB) individuals were particularly vulnerable to the negative effects of social isolation and financial instability resulting from COVID-19. The present study examined the effect of change in finances and access to TNB peer gatherings on anxiety and depression during the COVID-19 pandemic. Methods: Participants were 18 years and older (mean = 30) and completed prepandemic baseline (Fall 2019) and pandemic follow-up (Fall 2020) surveys. Multivariable regressions examined associations between mental health and change in (1) finances and (2) access to TNB peer gatherings (in person or online). Results: Of 780 participants, 50% reported that the COVID-19 pandemic had a negative impact on personal income and 58.3% reported negative impact on access to TNB peer gatherings. Depression and anxiety symptoms increased from prepandemic to follow-up, and most participants were above measurement cutoffs for clinical levels at both time points. Change in finances and access to TNB peer gatherings interacted with prepandemic depression scores to predict depression symptoms during the COVID-19 pandemic. For participants with high prepandemic depression scores, financial stability predicted pandemic depression scores comparable to that predicted by negative financial change. No interaction was found between these variables when predicting anxiety symptoms during the COVID-19 pandemic. Conclusion: Findings underscore the influence of inequality and prepandemic mental health when considering the impact of COVID-19 on wellbeing. Results suggest need for multifaceted programs and services, including financial support and meaningful TNB community engagement, to address barriers to health equity posed by systematic gender oppression.

Some Aspects of Oxidation and Reduction Processes in Ti-Al and Ti-Al-Nb Systems.

The oxidation of titanium and titanium aluminides has attracted the attention of scientists for many years because of their high-temperature application. The most popular method to investigate oxidation behavior is the measurement of alloy mass changes during exposure to elevated-temperature under isothermal or thermal cycling conditions. However, the thermogravimetric method is not enough to establish an oxidation mechanism. In this paper, the temperature-programmed oxidation (TPOx) and reduction (TPR) were applied for the Ti-Al and Ti-Al-Nb systems, which was a new experimental concept which revealed interesting phenomena. Although oxidation of titanium alloys is well-described in the literature, not many papers present at the same time reduction of oxidized alloys. The results presented in the paper concentrated on the first stages of oxidation, which are scarcely described in the literature, but are important to understand the oxidation mechanism. Comparison between powder and bulk samples with similar compositions revealed essential differences in the oxidation mechanism.

Dense T-Nb2O5/Carbon Microspheres for Ultrafast-(Dis)charge and High-Loading Lithium-Ion Batteries.

Orthorhombic niobium pentoxide (T-Nb2O5) is regarded as a potential anode material for lithium-ion batteries (LIBs) due to ultrafast charge/discharge and high safety. However, the poor electronic conductivity and low mass loading of nanostructured T-Nb2O5 limit its practical application in LIBs. Herein, we design and construct dense microspheres consisting of nanostructured T-Nb2O5 embedded in amorphous N-doped carbon (Nb2O5@NC) via a facile method to achieve fast ionic and electronic transport as well as a high mass loading. The dense micro-sized particles with an interconnected carbon network avoid the low mass loading and volumetric energy density of conventional nanostructures. Interconnected pores in the range of a few nanometers are also formed in the Nb2O5@NC microspheres. Notably, at a high mass loading of 12.8 mg cm-2, Nb2O5@NC can achieve a high specific capacity of 171.5 mAh g-1 and an areal capacity of 2.05 mAh cm-2, showing its high lithium storage capacity. The intercalation reaction mechanism with a small volume change during cycling at both crystal lattice and microsphere levels is confirmed by in situ X-ray diffraction and in situ high-resolution transmission electron microscopy. The elegant structure and the electrochemical reaction mechanism disclosed in the work is important for designing ultrafast-(dis)charge electrode materials.

Triple Conductive Wiring by Electron Doping, Chelation Coating and Electrochemical Conversion in Fluffy Nb2 O5 Anodes for Fast-Charging Li-Ion Batteries.

High-rate anode material is the kernel of developing fast-charging lithium ion batteries (LIBs). T-Nb2 O5 , well-known for its "room and pillar" structure and bulk pseudocapacitive effect, is expected to enable the fast lithium (de)intercalation. But this property is still limited by the low electronic conductivity or insufficient wiring manner. Herein, a strategy of triple conductive wiring through electron doping, chelation coating, and electrochemical conversion inside the microsized porous spheres consisting of dendrite-like T-Nb2 O5 primary particles is proposed to achieve the fast-charging and durable anodes for LIBs. The penetrative implanting of conformal carbon coating (derivative from polydopamine chelate) and NbO domains (induced by excess discharging) reinforces the global supply of electronically conductive wires, apart from those from Co/Mn heteroatom or O vacancy doping. The polydopamine etching on T-Nb2 O5 spheres promotes their evolution into fluffy morphology with better electrolyte infiltration. The synergic electron and ion wiring at different scales endow the modified T-Nb2 O5 anode with ultralong cycling life (143 mAh g-1 at 1 A g-1 after 8500 cycles) and high-rate performance (144.1 mAh g-1 at 10.0 A g-1 ). The permeation of multiple electron wires also enables a high mass loading of T-Nb2 O5 (4.5 mg cm-2 ) with a high areal capacity of 0.668 mAh cm-2 even after 150 cycles.

The clinical prognostic value of PD-L1 after concurrent chemoradiotherapy in Chinese nasopharyngeal carcinoma patients.

BACKGROUND: Although immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of nasopharyngeal carcinoma (NPC), it is still the second- or third-line treatment after the failure of radiotherapy or chemotherapy. In this study, we aimed to investigate the impact of concurrent chemoradiotherapy (CCRT) on programmed death-ligand 1 (PD-L1) protein expression in NPC patients. METHODS: We enrolled 24 NPC patients treated with intensity-modulated radiation therapy (IMRT) combined with cisplatin CCRT. PD-L1 expression was evaluated by immunohistochemistry, and next-generation sequencing and annotation were performed to determine the genetic alteration after CCRT. RESULTS: Our results showed that patients with a high expression of PD-L1 were more inclined to a complete response (CR) to chemoradiotherapy, as opposed to a partial response (PR) (P<0.05). Moreover, the mean values of the tumor mutation burden (TMB) and the tumor neoantigen burden (TNB) in the PD-L1 positive group were significantly lower than that of the PD-L1 negative group in our cohort. CONCLUSIONS: We confirmed that the TMB and TNB may be potential clinical indicators in NPC treatment, and PD-L1 expression may be a clinical biomarker in NPC chemoradiotherapy. Finally, through next-generation sequencing and annotation, we found that the most frequent driver gene mutations in NPC were TET2, TP53, and MAPK.

TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL.

The therapeutic potential of targeting CD19 in B cell malignancies has garnered attention in the past decade, resulting in the introduction of novel immunotherapy agents. Encouraging clinical data have been reported for T cell-based targeting agents, such as anti-CD19/CD3 bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR)-T therapies, for acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma (B-NHL). However, clinical use of both blinatumomab and CAR-T therapies has been limited due to unfavorable pharmacokinetics (PK), significant toxicity associated with cytokine release syndrome and neurotoxicity, and manufacturing challenges. We present here a fully human CD19xCD3 bispecific antibody (TNB-486) for the treatment of B-NHL that could address the limitations of the current approved treatments. In the presence of CD19+ target cells and T cells, TNB-486 induces tumor cell lysis with minimal cytokine release, when compared to a positive control. In vivo, TNB-486 clears CD19+ tumor cells in immunocompromised mice in the presence of human peripheral blood mononuclear cells in multiple models. Additionally, the PK of TNB-486 in mice or cynomolgus monkeys is similar to conventional antibodies. This new T cell engaging bispecific antibody targeting CD19 represents a novel therapeutic that induces potent T cell-mediated tumor-cell cytotoxicity uncoupled from high levels of cytokine release, making it an attractive candidate for B-NHL therapy.

Pressure induced structural behavior of energetic cocrystal TNT/TNB: a density functional theory study.

In order to find out the relationship between external pressures and properties of energetic materials, we used the density functional theory (DFT) method to investigate the structural, electronic, and absorption properties of crystalline 2,4,6-trinitrotoluene (TNT)/2,4,6-trinitrotoluene (TNB) under hydrostatic compression of 0-100 GPa. By analyzing the change of lattice constants (a, b, and c) of TNT/TNB under compression conditions, we found that variation tendency of the lattice constants was anisotropic. The b-axis is much stiffer than that along the a- and c-axes, which indicates that the TNT/TNB crystal is anisotropic within a certain pressure region. The pressure-induced structure transformation results in the new covalent bonds O11-C13, O12-C11, O8-C4, and O1-C12 at 60 GPa, and O4-C5 at 80 GPa, respectively. By analyzing the band structure and density of states of TNT/TNB in the pressure range over 40 GPa, the electronic structure of TNT/TNB changed to metallic system, which indicated it becomes more sensitivity under high pressures. The pressure-induced structure transformation of TNT/TNB also contributed to the relatively high optical activity of TNT/TNB at 70 GPa.

Stabilization of an abasic site paired against an unnatural triazolyl nitrobenzene nucleoside.

An abasic site is the most frequently observed among the various forms of DNA lesions in genomic DNA. If left unrepaired, an abasic site might turn out to be a principle cause for deleterious mutations and can be threat to cellular survival. Thus, to keep cellular integrity and measure the extent of DNA damage, recognition and stabilization of the abasic sites (apurinic/apyrimidinic site = Ap) are essential. Further, it is crucial to detect and stabilise the abasic site for towards the development of new diagnostics and chemotherapeutics. Herein, we report the stabilization of an abasic DNA duplex wherein the abasic site paired against a novel unnatural nucleoside, triazolylnitrobenzene (TNBBAc). This nucleoside is bulky and exhibits, high polarizability and good stacking propensity. Robust hetero-pair stabilization is another feature of it. Therefore, it is interesting to study the stabilization of an abasic DNA containing a synthesized triazolylnitrobenzene nucleoside TNBBAc We planned to study the thermal as well as the thermodynamic origin of abasic DNA stabilization by our synthesized oligonucleotide probe containing TNBBAc nucleoside. We observed that the nucleoside TNBBAc offered good thermal stabilization of a TNBBAc-Φ duplex via strong intercalative stacking interaction alongside an abasic site. The UV-visible spectroscopic study supported the intercalative stacking interaction. The stabilization though is marginal, but it would shed light on the design of bases of significant volume to stabilise abasic DNA to a greater extent.

Characterization and effect of metal ions on the formation of the Thermus thermophilus Sco mixed disulfide intermediate.

The Sco protein from Thermus thermophilus has previously been shown to perform a disulfide bond reduction in the CuA protein from T. thermophilus, which is a soluble protein engineered from subunit II of cytochrome ba 3 oxidase that lacks the transmembrane helix. The native cysteines on TtSco and TtCuA were mutated to serine residues to probe the reactivities of the individual cysteines. Conjugation of TNB to the remaining cysteine in TtCuA and subsequent release upon incubation with the complementary TtSco protein demonstrated the formation of the mixed disulfide intermediate. The cysteine of TtSco that attacks the disulfide bond in the target TtCuA protein was determined to be TtSco Cysteine 49. This cysteine is likely more reactive than Cysteine 53 due to a higher degree of solvent exposure. Removal of the metal binding histidine, His 139, does not change MDI formation. However, altering the arginine adjacent to the reactive cysteine in Sco (Arginine 48) does alter the formation of the MDI. Binding of Cu2+ or Cu+ to TtSco prior to reaction with TtCuA was found to preclude formation of the mixed disulfide intermediate. These results shed light on a mechanism of disulfide bond reduction by the TtSco protein and may point to a possible role of metal binding in regulating the activity. IMPORTANCE: The function of Sco is at the center of many studies. The disulfide bond reduction in CuA by Sco is investigated herein and the effect of metal ions on the ability to reduce and form a mixed disulfide intermediate are also probed.