ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis.

Only a small proportion of patients with cancer show lasting responses to immune checkpoint blockade (ICB)-based monotherapies. The RNA-editing enzyme ADAR1 is an emerging determinant of resistance to ICB therapy and prevents ICB responsiveness by repressing immunogenic double-stranded RNAs (dsRNAs), such as those arising from the dysregulated expression of endogenous retroviral elements (EREs)1-4. These dsRNAs trigger an interferon-dependent antitumour response by activating A-form dsRNA (A-RNA)-sensing proteins such as MDA-5 and PKR5. Here we show that ADAR1 also prevents the accrual of endogenous Z-form dsRNA elements (Z-RNAs), which were enriched in the 3' untranslated regions of interferon-stimulated mRNAs. Depletion or mutation of ADAR1 resulted in Z-RNA accumulation and activation of the Z-RNA sensor ZBP1, which culminated in RIPK3-mediated necroptosis. As no clinically viable ADAR1 inhibitors currently exist, we searched for a compound that can override the requirement for ADAR1 inhibition and directly activate ZBP1. We identified a small molecule, the curaxin CBL0137, which potently activates ZBP1 by triggering Z-DNA formation in cells. CBL0137 induced ZBP1-dependent necroptosis in cancer-associated fibroblasts and reversed ICB unresponsiveness in mouse models of melanoma. Collectively, these results demonstrate that ADAR1 represses endogenous Z-RNAs and identifies ZBP1-mediated necroptosis as a new determinant of tumour immunogenicity masked by ADAR1. Therapeutic activation of ZBP1-induced necroptosis provides a readily translatable avenue for rekindling the immune responsiveness of ICB-resistant human cancers.

Composite capillary carbon tube Nb18W16O93as advanced anode material for aqueous ion capacitors.

Niobium-tungsten bimetal oxides have received wide attention due to their excellent lattice properties. In this work, Nb18W16O93(NbWO) with a tetragonal tungsten bronze structure was synthesized by simple hydrothermal method. NbWO was modified to provide high specific surface area via combining with hollow carbon nanotubes. Meanwhile, NbWO grows along the tube wall of carbon nanotubes, thus buffering the volume effect of NbWO particles. Also, the migration distance of Li-ion is effectively shortened, as well as the improved ion transfer efficiency and the reaction kinetics. In addition, carbon tube can enhance conductivity of NbWO, contributing to outstanding charge storage capacity and rate energy. Precisely, NbWO@C as electrode possesses large specific capacity (249.6 F g-1at 0.5 A g-1) and good rate performance (55.9% capacity retention from 0.5 to 2 A g-1). The aqueous Li-ion capacitor presents the advantages of high safety, low cost and good environmental friendliness. An asymmetric aqueous capacitor AC//NbWO@C, based on 'water-in-salt' electrolyte with high concentration lithium acetate, exhibits a large energy density of 43.2 Wh kg-1and a power density of 9 kW kg-1. Generally, NbWO@C as anode materials shows superior application perspective.

Oligonucleotides DNA containing 8-trifluoromethyl-2'-deoxyguanosine for observing Z-DNA structure.

Z-DNA is known to be a left-handed alternative form of DNA and has important biological roles as well as being related to cancer and other genetic diseases. It is therefore important to investigate Z-DNA structure and related biological events in living cells. However, the development of molecular probes for the observation of Z-DNA structures inside living cells has not yet been realized. Here, we have succeeded in developing site-specific trifluoromethyl oligonucleotide DNA by incorporation of 8-trifluoromethyl-2'-deoxyguanosine (FG). 2D NMR strongly suggested that FG adopted a syn conformation. Trifluoromethyl oligonucleotides dramatically stabilized Z-DNA, even under physiological salt concentrations. Furthermore, the trifluoromethyl DNA can be used to directly observe Z-form DNA structure and interaction of DNA with proteins in vitro, as well as in living human cells by19F NMR spectroscopy for the first time. These results provide valuable information to allow understanding of the structure and function of Z-DNA.

Tuning of the Network Dimensionality and Photoluminescent Properties in Homo- and Heteroleptic Lanthanide Coordination Polymers.

Targeted synthesis, through a heteroleptic methodology, has resulted in three types of lanthanide (Ln) coordination polymers (CPs) with tailored dimensionality, tunable photoluminescent colors, and distinct luminescence quenching upon UV and X-ray irradiation. The homoleptic Ln(tpbz)(NO3)2 [CP-1; tpbz = 4-(2,2':6',2″-terpyridin-4'-yl)benzoate] is assembled from Ln cations and bridging tpbz ligands, accompanied by the decoration of NO3- anions, forming a one-dimensional (1D) chain structure. The presence of ancillary dicarboxylate linkers, 1,4-benzenedicarboxylate (bdc) and 2,5-thiophenedicarboxylate (tdc), promotes additional bridging between 1D chains to form a two-dimensional layer and a three-dimensional framework for Ln(tpbz)(bdc) (CP-2) and Ln(tpbz)(tdc) (CP-3), respectively. The multicolor and luminescence properties of the obtained CPs were investigated, displaying typical red EuIII-based and green TbIII-based emissions. The SmIII-bearing CP-1-CP-3, however, exhibit diverse ratiometric LnIII- and ligand-based emissions, with the photoluminescent colors varying from pink to orange to cyan. Notably, the TbIII-containing CP-1-CP-3 display distinct luminescence quenching upon continuous exposure to UV and X-ray irradiation. To our best knowledge, CP-2-Tb represents one of the most sensitive UV dosage probes (3.2 × 10-7 J) among all CPs.

Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells.

Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA.

Structural Complexity and Magnetic Orderings in a Large Family of 3d-4f Heterobimetallic Sulfates.

The synthesis of a large family of heterobimetallic lanthanide copper sulfates was realized via stoichiometric hydrothermal reactions among Ln2O3, CuO, and H2SO4, giving rise to four distinct phases, namely Ln2Cu(SO4)2(OH)4 (Ln = Sm-Ho) (LnCuSO4-1), Ln4Cu(SO4)2(OH)10 (Ln = Tm-Lu) (LnCuSO4-2), LnCu(SO4)(OH)3 (Ln = Nd-Gd, except Pm) (LnCuSO4-3), and LnCu(SO4)(OH)3 (Ln = Dy-Lu) (LnCuSO4-4), with completely different topologies. The passage from LnCuSO4-1 and LnCuSO4-3 to LnCuSO4-2 and LnCuSO4-4 across the 4f series, respectively, can be ascribed to the effect of lanthanide contraction, which progressively induces shrinking of the Ln-O distance, reduction in the Ln coordination number, and eventually structural transitions. The incorporation of identical 3d-4f metal ions into different spin-lattices, in conjunction with substitution of diverse Ln3+ cations within the same spin-lattice, gives rise to tunable magnetic properties varying from ferromagnetic ordering in GdCuSO4-3 and HoCuSO4-4 to antiferromagnetic ordering in YbCuSO4-4, and to paramagnetic correlations found in GdCuSO4-1 and YbCuSO4-2.

Investigation of the local structure of molten ThF4-LiF and ThF4-LiF-BeF2 mixtures by high-temperature X-ray absorption spectroscopy and molecular-dynamics simulation.

The microscopic structures of ThF4-LiF and ThF4-LiF-BeF2 molten salts have been systematically investigated by in situ high-temperature X-ray absorption fine-structure (XAFS) spectroscopy combined with molecular-dynamics (MD) simulations. The results reveal that the local structure of thorium ions was much more disordered in the molten state of the ThF4-LiF-BeF2 salt than that in ThF4-LiF, implying that the Th and F ions were exchanged more frequently in the presence of Be ions. The structures of medium-range-ordered coordination shells (such as Th-F2nd and Th-Th) have been emphasized by experimental and theoretical XAFS analysis, and they play a significant role in transport properties. Using MD simulations, the bonding properties in the molten ThF4-LiF and ThF4-LiF-BeF2 mixtures were evaluated, confirming the above conclusion. This research is, to the best of our knowledge, the first systematic study on the ThF4-LiF-BeF2 molten salt via quantitative in situ XAFS analysis and MD simulations.

Characterization of human telomere RNA G-quadruplex structures in vitro and in living cells using 19F NMR spectroscopy.

Human telomeric RNA has been identified as a key component of the telomere machinery. Recently, the growing evidence suggests that the telomeric RNA forms G-quadruplex structures to play an important role in telomere protection and regulation. In the present studies, we developed a 19F NMR spectroscopy method to investigate the telomeric RNA G-quadruplex structures in vitro and in living cells. We demonstrated that the simplicity and sensitivity of 19F NMR approach can be used to directly observe the dimeric and two-subunits stacked G-quadruplexes in vitro and in living cells and quantitatively characterize the thermodynamic properties of the G-quadruplexes. By employing the 19F NMR in living cell experiment, we confirmed for the first time that the higher-order G-quadruplex exists in cells. We further demonstrated that telomere RNA G-quadruplexes are converted to the higher-order G-quadruplex under molecular crowding condition, a cell-like environment. We also show that the higher-order G-quadruplex has high thermal stability in crowded solutions. The finding provides new insight into the structural behavior of telomere RNA G-quadruplex in living cells. These results open new avenues for the investigation of G-quadruplex structures in vitro and in living cells.

A Large Family of Centrosymmetric and Chiral f-Element-Bearing Iodate Selenates Exhibiting Coordination Number and Dimensional Reductions.

The exploration of phase formation in the f-element-bearing iodate selenate system has resulted in 14 novel rare-earth-containing iodate selenates, Ln(IO3)(SeO4) (Ln = La, Ce, Pr, Nd; LnISeO-1), Ln(IO3)(SeO4)(H2O) (Ln = Sm, Eu; LnISeO-2), and Ln(IO3)(SeO4)(H2O)2·H2O (Ln = Gd, Dy, Ho, Er, Tm, Yb, Lu, Y; LnISeO-3), as well as two new thorium iodate selenates, Th(OH)(IO3)(SeO4)(H2O) (ThISeO-1) and Th(IO3)2(SeO4) (ThISeO-2). LnISeO-3 and ThISeO-2 crystallize in the chiral space group P212121, while LnISeO-1, LnISeO-2, and ThISeO-1 crystallize in the centrosymmetric space group P21/c. The numbers of both coordinating and hydrating water molecules crystallized in LnISeO-1, LnISeO-2, and LnISeO-3 increase along these three series, in line with the increasingly negative values of hydration enthalpies of heavier trivalent lanthanide ions. Such a systematic change in compositions, especially the first coordination sphere of Ln, further induces structural rearrangements, including coordination number and dimensional reductions. More specifically, the structures of LnISeO-1, LnISeO-2, and LnISeO-3 have undergone transitions from 2D Ln-oxo layers with 10-coordinate Ln centers to 1D Ln-oxo chains with 9-coordinate Ln centers and then to 0D Ln-oxo monomers with 8-coordinate Ln centers, respectively. The formation and characterization of this large family of Ln/Th iodate selenates suggest that such a mixed-anion system not only exhibits richer structural chemistry but also can be capable of generating intriguing properties, such as the second-harmonic generation (SHG) effect.

In Situ Reduction from Uranyl Ion into a Tetravalent Uranium Trimer and Hexamer Featuring Ion-Exchange Properties and the Alexandrite Effect.

By utilizing zinc amalgam as an in situ reductant and pH regulator, mild hydrothermal reaction between UO2(CH3COO)2·2H2O, H2SO4, and Cs2CO3 or between UO2(CH3COO)2·2H2O, C2H4(SO3H)2, and K2CO3 yielded a novel cesium UIV sulfate trimer Cs4[U3O(SO4)7]·2.2H2O (1) and a new potassium UIV disulfonic hexamer K[U6O4(OH)5(H2O)5][C2H4(SO3)2]6·6H2O (2), respectively. Compound 1 features a lamellar structure with a honeycomb lattice, and it represents an unprecedented trimeric UIV cluster composed of purely inorganic moieties. Complex 2 is built from hexanuclear U4+ cores and K+ ions interconnected by µ5-[C2H4(SO3)2]2- groups, leading to the construction of an extended framework rather than commonly observed discrete, neutral molecular sulfonate clusters. The various binding modes of the sulfate and disulfonate groups, especially the multidentate ones, enable additional bridging between metal ions, which promotes oligomerization and isolation of polynuclear species. Furthermore, compound 1 exhibits both ion-exchange properties and the Alexandrite effect, and it is the second example of a uranium complex without chromic functional ligands displaying the latter feature.

Immobilization of Alkali Metal Fluorides via Recrystallization in a Cationic Lamellar Material, [Th(MoO4)(H2O)4Cl]Cl·H2O.

Searching for cationic extended materials with a capacity for anion exchange resulted in a unique thorium molybdate chloride (TMC) with the formula of [Th(MoO4)(H2O)4Cl]Cl·H2O. The structure of TMC is composed of zigzagging cationic layers [Th(MoO4)(H2O)4Cl]+ with Cl- as interlamellar charge-balancing anions. Instead of performing ion exchange, alkali thorium fluorides were formed after soaking TMC in AF (A = Na, K, and Cs) solutions. The mechanism of AF immobilization is elucidated by the combination of SEM-EDS, PXRD, FTIR, and EXAFS spectroscopy. It was observed that four water molecules coordinating with the Th4+ center in TMC are vulnerable to competition with F-, due to the formation of more favorable Th-F bonds compared to Th-OH2. This leads to a single crystal-to-polycrystalline transformation via a pathway of recrystallization to form alkali thorium fluorides.

Uranium-Induced Changes in Crystal-Field and Covalency Effects of Th4+ in Th1- xU xO2 Mixed Oxides Probed by High-Resolution X-ray Absorption Spectroscopy.

Knowledge of the local Th structure is a prerequisite for a better understanding of the physicochemical properties of the thorium-based mixed oxides (Th-MOX) involved in the Th-based nuclear fuel cycle. The crystalline electric field (CEF) splitting of the 6d shell in Th1- xU xO2 ( x = 0.25, 0.5, 0.75) solid solution was probed by the Th L3 edge high-energy-resolution fluorescence-detected (HERFD) X-ray absorption near-edge spectroscopy (XANES) collected at the Lß5 emission line, which cannot be obtained by conventional X-ray absorption methods. The detected CEF split between the 6d eg and t2g orbitals in ThO2 consisting of ordered Th-O8 cubes with cubic symmetry is ∼3.5 eV for the Th4+ ion. Because the split peaks of the white line corresponding to the crystal-field splitting of the unoccupied 6d states were resolved in the HERFD-XANES spectra, the analysis of these split peaks combined with first-principles calculations revealed that an increase of the U content involves the distortion of the Th-O8 cubes in the Th1- xU xO2 mixed oxides. The lower symmetry of the Th-O8 cube induced by the incorporated U tends to reduce the local crystal-field around Th4+ as well as the hybridization of Th 6t2g-O 2p which is mainly responsible for the covalent property of the Th-O bond. The phenomenon is noticeable in Th0.25U0.75O2, whose CEF splitting is decreased by approximately 10%, and covalent mixing between Th 6d t2g and O 2p orbitals is substantially reduced compared to that of pure ThO2.

2'-O-Methyl-8-methylguanosine as a Z-Form RNA Stabilizer for Structural and Functional Study of Z-RNA.

In contrast to Z-DNA that was stabilized and well-studied for its structure by chemical approaches, the stabilization and structural study of Z-RNA remains a challenge. In this study, we developed a Z-form RNA stabilizer m8Gm, and demonstrated that incorporation of m8Gm into RNA can markedly stabilize the Z-RNA at low salt conditions. Using the m8Gm-contained Z-RNA, we determined the structure of Z-RNA and investigated the interaction of protein and Z-RNA.

Structure-Dependent Binding of hnRNPA1 to Telomere RNA.

Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an RNA-binding protein involved in the telomere maintenance machinery. To date, little is known about how hnRNPA1 binds to telomeric RNA. In this study, we investigated the binding affinity and recognition mechanism of telomere RNA with the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking method, we showed that the telomere RNA G-quadruplex with loops is important in the interaction of telomere RNA with hnRNPA1. Using small-molecule probes, we directly visualized the complex formed by the telomere RNA G-quadruplex and hnRNPA1 in vitro and in live cells. The results suggested that the structure-dependent binding of hnRNPA1 to telomere RNA regulates the telomere function. Therefore, our study provides new insights into the interactions between the RNA G-quadruplex and proteins at the telomere.

A Breakthrough Efficiency of 19.9% Obtained in Inverted Perovskite Solar Cells by Using an Efficient Trap State Passivator Cu(thiourea)I.

It is extremely significant to study the trap state passivation and minimize the trap states of perovskite to achieve high-performance perovskite solar cells (PSCs). Here, we have first revealed and demonstrated that a novel p-type conductor Cu(thiourea)I [Cu(Tu)I] incorporated in perovskite layer can effectively passivate the trap states of perovskite via interacting with the under-coordinated metal cations and halide anions at the perovskite crystal surface. The trap state energy level of perovskite can be shallowed from 0.35-0.45 eV to 0.25-0.35 eV. In addition, the incorporated Cu(Tu)I can participate in constructing the p-i bulk heterojunctions with perovskite, leading to an increase of the depletion width from 126 to 265 nm, which is advantageous for accelerating hole transport and reducing charge carrier recombination. For these two synergistic effects, Cu(Tu)I can play a much better role than that of the traditional p-type conductor CuI, probably due to its identical valence band maximum with that of perovskite, which enables to not only lower the trap state energy level to a greater extent but also eliminate the potential wells for holes at the p-i heterojunctions. After optimization, a breakthrough efficiency of 19.9% has been obtained in the inverted PSCs with Cu(Tu)I as the trap state passivator of perovskite.

A multi-functional guanine derivative for studying the DNA G-quadruplex structure.

In the present study, we developed a multi-functional guanine derivative, 8FG, as a G-quadruplex stabilizer, a fluorescent probe for the detection of G-quadruplex formation, and a 19F sensor for the observation of the G-quadruplex. We demonstrate that the functional nucleoside bearing a 3,5-bis(trifluoromethyl)benzene group at the 8-position of guanine stabilizes the DNA G-quadruplex structure and fluoresces following the G-quadruplex formation. Furthermore, we show that the functional sensor can be used to directly observe DNA G-quadruplexes by 19F-NMR in living cells. To our knowledge, this is the first study showing that the nucleoside derivative simultaneously allows for three kinds of functions at a single G-quadruplex DNA. Our results suggest that the multi-functional nucleoside derivative can be broadly used for studying the G-quadruplex structure and serves as a powerful tool for examining the molecular basis of G-quadruplex formation in vitro and in living cells.

Probing the Influence of Acidity and Temperature to Th(IV) on Hydrolysis, Nucleation, and Structural Topology.

Systematic control of the molar ratio between thorium hydroxides and selenic acid and their reaction temperature under hydrothermal conditions results in four novel thorium-based selenate complexes, namely, [Th8O4(OH)8(SeO4)6(H2O)16]·(SeO4)2·13H2O (Th-1), [Th8O4(OH)8(SeO4)8(H2O)13]·7H2O (Th-2), Th(OH)2(SeO4)H2O (Th-3), and Th3(SeO4)6(H2O)6·2.5H2O (Th-4), as well as the thorium mixed selenite selenate compound Th(SeO3)(SeO4) (Th-5). Smaller [H2SeO4]/[Th(IV)] ratio or lower temperature give rise to the formation of octameric [Th8(µ3-O)4(µ2-OH)8]16+ cores in Th-1/Th-2 and infinite [Th(µ2-OH)2H2O]2+ chains in Th-3, respectively. Increasing the [H2SeO4]/[Th(IV)] ratio or elevating the temperature generates a microporous (11.3 Å voids) open-framework Th-4, a monomeric thorium species without oxo/hydroxyl ligands, and a three-dimensional thorium structure Th-5. Formation of these compounds suggests that variables including acidity and temperature play a critical role in the hydrolysis and oligomerization of ThIV ions. Increasing acidity limits the deprotonation of water molecules and formation of nucleophilic hydroxo/oxo-aquo Th species, and high temperature appears to suppress the olation/oxolation hydrolysis reactions, which in both ways limit the formation of the thorium oligomers.

Photochemically engineering the metal-semiconductor interface for room-temperature transfer hydrogenation of nitroarenes with formic acid.

A mild photochemical approach was applied to construct highly coupled metal-semiconductor dyads, which were found to efficiently facilitate the hydrogenation of nitrobenzene. Aniline was produced in excellent yield (>99 %, TOF: 1183) using formic acid as hydrogen source and water as solvent at room temperature. This general and green catalytic process is applicable to a wide range of nitroarenes without the involvement of high-pressure gases or sacrificial additives.

Ruthenium nanoparticles supported on CeO2 for catalytic permanganate oxidation of butylparaben.

This study developed a heterogeneous catalytic permanganate oxidation system with ceria supported ruthenium, Ru/CeO2 (0.8‰ as Ru), as catalyst for the first time. The catalytic performance of Ru/CeO2 toward butylparaben (BP) oxidation by permanganate was strongly dependent on its dosage, pH, permanganate concentration and temperature. The presence of 1.0 g L(-1) Ru/CeO2 increased the oxidation rate of BP by permanganate at pH 4.0-8.0 by 3-96 times. The increase in Ru/CeO2 dosage led to a progressive enhancement in the oxidation rate of BP by permanganate at neutral pH. The XANES analysis revealed that (1) Ru was deposited on the surface of CeO2 as Ru(III); (2) Ru(III) was oxidized by permanganate to its higher oxidation state Ru(VI) and Ru(VII), which acted as the co-oxidants in BP oxidation; (3) Ru(VI) and Ru(VII) were reduced by BP to its initial state of Ru(III). Therefore, Ru/CeO2 acted as an electron shuttle in catalytic permanganate oxidation process. LC-MS/MS analysis implied that BP was initially attacked by permanganate or Ru(VI) and Ru(VII) at the aromatic ring, leading to the formation of various hydroxyl-substituted and ring-opening products. Ru/CeO2 could maintain its catalytic activity during the six successive runs. In conclusion, catalyzing permanganate oxidation with Ru/CeO2 is a promising technology for degrading phenolic pollutants in water treatment.

Oligonucleotide Containing 8-Trifluoromethyl-2'-Deoxyguanosine as a Z-DNA Probe.

Z-DNA structure is a noncanonical left-handed alternative form of DNA, which has been suggested to be biologically important and is related to several genetic diseases and cancer. Therefore, investigation of Z-DNA structure associated with biological events is of great importance to understanding the functions of these molecules. Here, we described the development of a trifluoromethyl labeled deoxyguanosine derivative and employed it as a 19F NMR probe to study Z-form DNA structure in vitro and in living cells.