Bifunctional Role Research Articles

Toward Shuttle‐Free Zn–I2 Battery: Anchoring and Catalyzing Iodine Conversion by High‐Density P‐Doping Sites in Carbon Host

AbstractZn–iodine (I2) battery, as a promising energy storage device, especially under high I2 loading, is harassed by the shuttle effect of the soluble polyiodide intermediates. Herein, the bifunctional role of 2D carbon nanosponge with rich P‐dopant (4.2 at%) and large specific surface area (1966 m2 g−1) in anchoring I2/Ix− (x = 1, 3 or 5) and catalyzing their mutual conversion is reported. Both experiment and computational results reveal the transfer of electrons from the P‐doped site to iodine species, showing strong interfacial interaction. When being used as a host, it possesses high specific capture capacity for I2 (3.34 giodine g−1 or 1.6 mgiodine m−2) and Ix− (6.12 gtriiodide g−1 or 3.1 mgtriiodide m−2), which thus effectively suppresses the shuttle effect, supported by in situ UV–vis and Raman spectra. In addition to the strong interfacial interaction that favors iodine conversion, the P‐doped sites can also catalyze the conversion of I5− to I2, which is the rate‐determining step. Consequently, Zn–I2 batteries under a high I2 content (70 wt%) deliver high specific capacity (220.3 mAh g−1), superior Coulombic efficiency (>99%), and low self‐discharge rate; moreover, they can also operate steadily at 2 A g−1 with ignorable capacity decay for 10 000 cycles.

Bifunctional Role of Monocyte Subsets in Modulating Radiotherapy Combined Intra-Tumor αCD40 Agonist Induced Abscopal Effect

Abscopal effect induced by radiotherapy and immune checkpoint blockade is a promising yet far from satisfactory strategy in clinical. The underlying immune mechanism, especially driven by monocytes remains poorly undefined. Monocytes consist of two phenotypically and functionally distinct subsets distinguished by expression of chemokine receptors CCR2 and CX3CR1: classical inflammatory Ly6ChiCCR2hi monocytes and nonclassical patrolling Ly6CloCCR2loCX3CR1hi monocytes. Monocytes differentiate and transit to other myeloid cells such as dendritic cells and macrophages according to various environmental cues. Herein we investigated the roles of monocyte subsets in modulating tumor control consisting of combination RT and myeloid checkpoint agonist αCD40 to specifically ignite myeloid cell activation. To establish abscopal model, contralateral tumors were implanted in each mouse, while only one side were treated with RT (8 Gy × 3) + αCD40 agonist (50 μg, intra-tumor). Tumor volume and mice survival were compared in each group (control, RT, αCD40 and RT + αCD40). Ccr2RFP/+ Cx3cr1GFP/+ (R2 × 3), Ccr2RFP/RFPCx3cr1+/+ (R2-KO) and Ccr2+/+Cx3cr1GFP/GFP (X3-KO) mice were used for cell tracking and to dissect chemokine receptor CCR2 and CX3CR1 on monocyte. Tumor infiltrating immune cells were analyzed by flowcytometry and RNA-seq. RT combined with αCD40 significantly dampened tumor growth on both ipsilateral and contralateral sides in abscopal model (p< 0.01), accompanied by upregulation of chemokine receptors CCR2 and CX3CR1 on myeloid cells were both increased in tumor and peripheral blood. Chemokine ligands CCL2, CCL3, CCL5, CCL7, CCL12 and CX3CL1 were upregulated in tumor after RT and αCD40 treatment, recruiting CCR2 and CX3CR1 expressing monocytes in situ. To elucidate the roles of CCR2 and CX3CR1 in mediating local and systemic anti-tumor immunity, R2 × 3, R2-KO and X3-KO mice with combined treatment were used. Tumor size on ipsilateral leg were similar among groups. However, tumor growth was significantly delayed on contralateral side in X3-KO mice while accelerated in R2-KO mice compared with that in R2 × 3 mice. Mechanistically, remarkable decrease of antigen presenting dendritic cells (MHCII+Ly6ChiCD11c+) were observed in R2-KO mice. Moreover, phagocytosis was strengthened in macrophages (F4/80+CD11b+) of X3-KO mice. CX3CR1 deletion ignite anti-tumor immunity elicited by RT and αCD40 through enhanced phagocytosis in macrophages, while CCR2 deletion renders inferior tumor control through reduction of dendritic cells. Preferential targeting nonclassical patrolling monocyte may lead to enhanced local and systemic tumor control.

Ionic liquids (ILs)-loaded hydrogels as a potential cleaning method of metallic stains for stone conservation

In the field of built heritage, the removal of reddish-brown and greenish stains presents a complex challenge frequently encountered by experts. Consequently, numerous studies strive to develop sustainable and respectful cleaning methods for conserving stone materials in their original esthetic state. In pursuit of this objective, agar hydrogels were here investigated as solid support, capitalizing on their slow-release capability and capacity to store chemical species. As chelating and biocidal loading, three different ionic liquids (ILs) (trihexyltetradecylphosphonium chloride (TP), bis(2-ethylhexyl) phosphate (BP), and Alicy (AL) and a mixture of Aliquat 336 and Cyanex 272 were tested for the controlled removal of iron and copper stains. The homogeneity and cleaning effectiveness of the different loaded agar hydrogels were assessed on artificial stains using a combination of micro-energy dispersive X-ray fluorescence (µ-ED-XRF) and Raman imaging analyses. The spectroscopic data were supported by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and colorimetric measurements. Additionally, the inhibitory effect on microbial growth of the most effective treatments was tested prior to their in situ application on naturally stained stones. The results indicated that agar provides suitable solid support to apply ILs, specifically highlighting the strong affinity of AL and BP for sequestering iron and copper ions, respectively, from stained stone surfaces. Furthermore, the disk-diffusion results evidenced that the proposed treatments could play a bi-functional role if a biocidal action is required to remove biological colonization, reaching nwhalo average values in the range of 0.6 - 0.8 against Micrococcus Luteus. Thus, this study showcases the potential of agar hydrogels loaded with ILs as a sustainable and gentle cleaning method in built heritage conservation.

Room-Temperature, Multigram-Scale Synthesis and Conversion Mechanism of Highly Luminescent Lead Sulfide Quantum Dots.

PbS quantum dots (QDs) are attractive near-infrared (NIR) materials, but traditional synthetic methods require inert atmosphere and/or high temperature. Herein we develop a facile, room-temperature synthetic route for in situ halide passivated PbS QDs through controllable reactions between lead halide, N,N'-diphenyl thiourea, and oleyamine (OLA) in toluene. Contrast experiments and theoretical calculations reveal that the OLA plays a bifunctional role as a mild base to initiate the formation of PbS monomers and as a dynamic ligand to control the crystallization of PbS QDs and further ligand exchange. The oleic acid-capped PbS QDs exhibit high photoluminescence quantum yields up to 45%. The scaled-up synthesis on multigram scales shows great batch-to-batch consistency. We further demonstrate high-power NIR light-emitting diodes using the PbS QDs as color converters, delivering NIR optical power of 9.2 mW at 160 mA. This work provides a simple and versatile synthetic route for high-quality PbS QDs and boosts the applications of NIR materials.

Heterogenous electromediated depolymerization of highly crystalline polyoxymethylene

Post-consumer plastic waste in the environment has driven the scientific community to develop deconstruction methods that yield valued substances from these synthetic macromolecules. Electrocatalysis is a well-established method for achieving challenging transformations in small molecule synthesis. Here we present the first electro-chemical depolymerization of polyoxymethylene—a highly crystalline engineering thermoplastic (Delrin®)—into its repolymerizable monomer, formaldehyde/1,3,5-trioxane, under ambient conditions. We investigate this electrochemical deconstruction by employing solvent screening, cyclic voltammetry, divided cell studies, electrolysis with redox mediators, small molecule model studies, and control experiments. Our findings determine that the reaction proceeds via a heterogeneous electro-mediated acid depolymerization mechanism. The bifunctional role of the co-solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is also revealed. This study demonstrates the potential of electromediated depolymerization serving as an important role in sustainable chemistry by merging the concepts of renewable energy and circular plastic economy.

Basis for high-affinity ethylene binding by the ethylene receptor ETR1 of Arabidopsis

The gaseous hormone ethylene is perceived in plants by membrane-bound receptors, the best studied of these being ETR1 from Arabidopsis. Ethylene receptors can mediate a response to ethylene concentrations at less than one part per billion; however, the mechanistic basis for such high-affinity ligand binding has remained elusive. Here we identify an Asp residue within the ETR1 transmembrane domain that plays a critical role in ethylene binding. Site-directed mutation of the Asp to Asn results in a functional receptor that has a reduced affinity for ethylene, but still mediates ethylene responses in planta. The Asp residue is highly conserved among ethylene receptor-like proteins in plants and bacteria, but Asn variants exist, pointing to the physiological relevance of modulating ethylene-binding kinetics. Our results also support a bifunctional role for the Asp residue in forming a polar bridge to a conserved Lys residue in the receptor to mediate changes in signaling output. We propose a new structural model for the mechanism of ethylene binding and signal transduction, one with similarities to that found in a mammalian olfactory receptor.

2D Mesoporous Zincophilic Sieve for High-Rate Sulfur-Based Aqueous Zinc Batteries.

Sulfur-based aqueous zinc batteries (SZBs) attract increasing interest due to their integrated high capacity, competitive energy density, and low cost. However, the hardly reported anodic polarization seriously deteriorates the lifespan and energy density of SZBs at a high current density. Here, we develop an integrated acid-assisted confined self-assembly method (ACSA) to elaborate a two-dimensional (2D) mesoporous zincophilic sieve (2DZS) as the kinetic interface. The as-prepared 2DZS interface presents a unique 2D nanosheet morphology with abundant zincophilic sites, hydrophobic properties, and small-sized mesopores. Therefore, the 2DZS interface plays a bifunctional role in reducing the nucleation and plateau overpotential: (a) accelerating the Zn2+ diffusion kinetics through the opened zincophilic channels and (b) inhibiting the kinetic competition of hydrogen evolution and dendrite growth via the significant solvation-sheath sieving effect. Therefore, the anodic polarization is reduced to 48 mV at 20 mA cm-2, and the full-battery polarization is reduced to 42% of an unmodified SZB. As a result, an ultrahigh energy density of 866 Wh kgsulfur-1 at 1 A g-1 and a long lifespan of 10,000 cycles at a high rate of 8 A g-1 are achieved.

Recent Update and Drug Target in Molecular and Pharmacological Insights into Autophagy Modulation in Cancer Treatment and Future Progress.

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine's effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment.

Confinement of MACl guest in 2D ZIF-8 triggers interface and bulk passivation for efficient and UV-stable perovskite solar cells

The MACl@ZIF-8 interlayer plays a bi-functional role in passivating buried interfaces and healing the defects in the bulk phase. As a result, significantly enhanced device performance is obtained with a champion PCE of 22.10%.

Bifunctional role of PDMS membrane in designing humidity-tolerant H2S chemiresistors with high selectivity.

A thermally evaporated hydrophobic PDMS membrane could significantly mitigate humidity interference/poisoning (without a decline in response at 50% RH for nearly 3 months) and enhance the selectivity of a CuCrO2 chemiresistor toward erosive H2S, offering an avenue for the practical applications of (H2S) chemiresistors in an ambient humid air atmosphere.

Unveiling the bifunctional role of morphological differences of self-supported Cu(OH)2 in electrocatalysis

Structure engineering of copper foil by an anodization strategy for developing an electrocatalyst with nanoneedles showed exceptional MOR and OER activity.

Bi-functional role of high charge mobility with 2D/2D interactions for effective PEC and visible photocatalysis in NiO/MoS2 nanocomposites

Bi-functional 2D–2D NiO/MoS2 exhibits superior photoactivity and hydrogen production due to homogenously dispersed layers, electronic conductivity, and interfacial charge coupling.

MoSe2-nanoflowers as bi-functional electro-catalyst: An efficient counter electrode material for dye-sensitized solar cells and electrode modifier for hydrazine sensor

In this study, we reported bi-functional role of molybdenum diselenide (MoSe2)-flowers as electro-catalyst for dye-sensitized solar cells (DSSCs) and electrochemical sensing applications. The counter electrode was fabricated by using MoSe2-flowers as counter electrode material. The highest power conversion efficiency (PCE) of ∼4.8% was obtained. In further studies, we constructed electrochemical sensor (hydrazine) by modifying the surface of glassy carbon electrode (GCE) with prepared MoSe2-flowers via drop casting method. The MoSe2/GCE showed good limit of detection of 1.3 μM including sensitivity of 0.419 μA/μM-cm2. The MoSe2/GCE also demonstrates selective nature for the determination of hydrazine.

Immobilization of Candida Rugosa lipase on Ca/Kit-6 used as bifunctional biocatalysts for the transesterification of coconut oil to biodiesel

Immobilization of Candida Rugosa lipase (CRL) on Ca doped Kit-6 solid was investigated via the adsorption method. Effects of the experimental parameters, such as pH value, temperature, time, and Ca content on the adsorption of CRL on Ca/Kit-6 were studied. In the Ca doped Ca/Kit-6 materials, Ca2+ coexisted in two environments: Ca2+ in CaO nanoparticles and in Ca-O-Si in the framework of Kit-6. There existed three kind of oxygen species: (1) lattice oxygen in CaO and SiO2; (2) Oxygen in structural defects; and (3) non-stoichiometric surface oxygen in OH form. The 0.5Ca/Kit-6 showed the most CRL immobilization capacity and stability under the optimal adsorption condition, which was correlated with its greater amount of basicity resulting from its more non-stoichiometric surface oxygen and oxygen in structural defects as well as more Ca2+ incorporation in the Kit-6 framework. In the production of biodiesel via transesterification of coconut oil, the catalysts showed better catalytic performance under weak basic than acidic condition. Under the optimal reaction conditions (40 °C, pH 7.5, 200 rpm, oil to methanol ratio 1:3 with stepwise addition of methanol, and 0.1 g of CRL/0.5Ca/Kit-6), the coconut oil conversion and biodiesel yield catalyzed with CRL/0.5Ca/Kit-6 was 95 and 98%, respectively. 10wt% water in the reaction mixture promoted the coconut oil transesterification to biodiesel. The CRL/0.5Ca/Kit-6 catalyst possessed bifunctional roles of the enzymatic catalysis role from immobilized CRL and the basic catalysis role from CaO doping. The CRL adsorption modes, water influence and the reaction mechanism of coconut oil transesterification were discussed.

A putative bifunctional CPD/ (6-4) photolyase from the cyanobacteria Synechococcus sp. PCC 7335 is encoded by a UV-B inducible operon: New insights into the evolution of photolyases.

Photosynthetic organisms are continuously exposed to solar ultraviolet radiation-B (UV-B) because of their autotrophic lifestyle. UV-B provokes DNA damage, such as cyclobutane pyrimidine dimers (CPD) or pyrimidine (6-4) pyrimidone photoproducts (6-4 PPs). The cryptochrome/photolyase family (CPF) comprises flavoproteins that can bind damaged or undamaged DNA. Photolyases (PHRs) are enzymes that repair either CPDs or 6-4 PPs. A natural bifunctional CPD/(6-4)- PHR (PhrSph98) was recently isolated from the UV-resistant bacteria Sphingomonas sp. UV9. In this work, phylogenetic studies of bifunctional CPD/(6-4)- photolyases and their evolutionary relationship with other CPF members were performed. Amino acids involved in electron transfer and binding to FAD cofactor and DNA lesions were conserved in proteins from proteobacteria, planctomycete, bacteroidete, acidobacteria and cyanobacteria clades. Genome analysis revealed that the cyanobacteria Synechococcus sp. PCC 7335 encodes a two-gene assembly operon coding for a PHR and a bifunctional CPD/(6-4) PHR- like. Operon structure was validated by RT-qPCR analysis and the polycistronic transcript accumulated after 15 min of UV-B irradiation. Conservation of structure and evolution is discussed. This study provides evidence for a UV-B inducible PHR operon that encodes a CPD/(6-4)- photolyase homolog with a putative bifunctional role in the repair of CPDs and 6-4 PPs damages in oxygenic photosynthetic organisms.

Photosynthesis assembling of ZCS/PO/Ni3Pi2 catalyst for three-stage photocatalytic water splitting into H2 and H2O2

Photocatalytic intermediate water splitting (PIWS) provides a promising route for hydrogen production as its high product value, favorable kinetics and easy separation. However, the traditional oxide and sulfide-based catalysts either respond to ultraviolet light or suffer from severe photocorrosion and sluggish kinetics, leading to poor conversion efficiency. Herein, we employ a two-step photosynthesis strategy to prepare an inexpensive phosphorus (PO) protection layer and nickel phosphate (Ni3Pi2) cocatalyst on the Zn0.14Cd0.86S (ZCS) photocatalyst, which shows a H2 and H2O2 evolution rate of 1.464 and 1.375 mmol h−1 g−1 in water splitting under 20 h visible light irradiation. The excellent PIWS performance originates from a combination of anti-photocorrosion ability of PO protection layer and bi-functional role of Ni3Pi2, which decompose into Ni2P and NiPi to enhance the H2 and H2O2 evolution. Moreover, the two-step photosynthesis process triggers photocatalytic partial water splitting (PPWS) by oxidizing NaH2PO2, with H2 evolution rate of 9.26 and 9.53 mmol h−1 g−1, respectively. This work develops a photosynthesis assembling of ZCS/PO/Ni3Pi2 catalyst, which not only presents superior performance for H2O2 evolution but also achieves a high average H2 production rate of 0.28 mmol h−1 under 25 h visible light irradiation by integrating the three-stage PPWS→PPWS→PIWS process.

FGF13-Sensitive Alteration of Parkin Safeguards Mitochondrial Homeostasis in Endothelium of Diabetic Nephropathy.

Studies of diabetic glomerular injury have raised the possibility of developing useful early biomarkers and therapeutic approaches for the treatment of type 2 diabetic nephropathy (T2DN). In this study, we found that FGF13 expression is induced in glomerular endothelial cells (GECs) during T2DN progression. Endothelial-specific deletion of Fgf13 potentially alleviates T2DN damage, while Fgf13 overexpression has the opposite effect. Mechanistically, Fgf13 deficiency results in improved mitochondrial homeostasis and endothelial barrier integrity in T2DN. Moreover, FGF13-sensitive alteration of Parkin safeguards mitochondrial homeostasis in endothelium of T2DN through promotion of mitophagy and inhibition of apoptosis. Additionally, it is confirmed that the beneficial effects of Fgf13 deficiency on T2DN are abolished by endothelial-specific double deletion of Fgf13 and Prkn. The effects of Fgf13 deficiency on mitophagy and apoptosis through Parkin-dependent regulation may be distinct and separable events under diabetic conditions. These data show that the bifunctional role of Fgf13 deficiency in promoting mitophagy and inhibiting apoptosis through Parkin can shape mitochondrial homeostasis regulation in GECs and T2DN progression. As a potential therapeutic target for prevention and control of T2DN, a mechanistic understanding of the biofunction of FGF13 may also be relevant to the pathogenesis of other FGF13- and Parkin-associated diseases.

Copper-Containing Artificial Polyenzymes as a Clickase for Bioorthogonal Chemistry.

Artificial polyenzymes (ArPoly) are tailored combinations of universal protein scaffolds and polymers newly proposed as promising alternatives to natural enzymes to expand the biocatalyst toolbox. The concept of ArPoly has been continuously extended to metal-containing ArPoly to overcome the drawbacks faced by conventional artificial metalloenzymes. Herein, we present a sustainable route to synthesize a novel water-soluble metalloenzyme for copper-catalyzed azide-alkyne cycloadditions in water with remarkable selectivity. In this case, synthetic l-proline monomers were polymerized onto bovine serum albumen in an aqueous medium via copper-mediated "grafting-from" atom-transfer radical polymerization, resulting in protein-polymer-copper conjugates named ArPolyclickase. The copper in ArPolyclickase plays pivotal bifunctional roles, not only as the catalyst for polymerization but also as the coordinated active site for alkyne-azide click catalysis. ArPolyclickase showcases high efficiency, substrate generality, regioselectivity, and ease of product separation for "click chemistry" in water. Notably, ArPolyclickase displays good biocompatibility without imposing copper toxicity on living cells, which offers the prospect for the upcoming bioorthogonal chemistry.

Nuclear Functions of KaeA, a Subunit of the KEOPS Complex in Aspergillus nidulans.

Kae1 is a subunit of the highly evolutionarily conserved KEOPS/EKC complex, which is involved in universal (t6A37) tRNA modification. Several reports have discussed the participation of this complex in transcription regulation in yeast and human cells, including our previous observations of KaeA, an Aspergillus nidulans homologue of Kae1p. The aim of this project was to confirm the role of KaeA in transcription, employing high-throughput transcriptomic (RNA-Seq and ChIP-Seq) and proteomic (LC-MS) analysis. We confirmed that KaeA is a subunit of the KEOPS complex in A. nidulans. An analysis of kaeA19 and kaeA25 mutants showed that, although the (t6A37) tRNA modification is unaffected in both mutants, they reveal significantly altered transcriptomes compared to the wild type. The finding that KaeA is localized in chromatin and identifying its protein partners allows us to postulate an additional nuclear function for the protein. Our data shed light on the universal bi-functional role of this factor and proves that the activity of this protein is not limited to tRNA modification in cytoplasm, but also affects the transcriptional activity of a number of nuclear genes. Data are available via the NCBI’s GEO database under identifiers GSE206830 (RNA-Seq) and GSE206874 (ChIP-Seq), and via ProteomeXchange with identifier PXD034554 (proteomic).

Structural Studies Reveal Unique Non-canonical Regulators of G Protein Signaling Homology (RH) Domains in Sorting Nexins

As a subgroup of sorting nexins (SNXs) that contain regulator of G protein signaling homology (RH) domain, SNX-RH proteins, including SNX13, SNX14 and SNX25, were proposed to play bifunctional roles in protein sorting and GPCR signaling regulation. However, mechanistic details of SNX-RH proteins functioning via RH domain remain to be illustrated. Here, we delineate crystal structures of the RH domains of SNX13 and SNX25, revealing a homodimer of SNX13 RH domain mediated by unique extended α4 and α5 helices, and a thiol modulated homodimer of SNX25-RH triggered by a unique cysteine on α6 helix. Further studies showed that RH domains of SNX-RH do not possess binding capacity toward Gα subunits, owing to the lack of critical residues for interaction. Thus, this study identifies a group of novel non-canonical RH domains that can act as a dimerization module in sorting nexins, which provides structural basis for mechanism studies on SNX-RH protein functions.