BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.

The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.

Synthesis of polyoxometalate-pillared Zn-Cr layered double hydroxides for photocatalytic CO2 reduction and H2O oxidation.

Polyoxometalate (POM)-pillared Zn-Cr layered double hydroxides (LDHs) exhibited high photocatalytic activities in CO2 reduction and H2O oxidation reactions. For CO2 reduction in pure water, the CO production was 1.17 µmol g-1 after a 24 h reaction. For O2 evolution in NaIO3 solution, the O2 production reached 148.1 µmol g-1 after a 6 hour reaction. A mechanism study indicated that the electron transfer from Zn-Cr LDHs to POMs (SiW12O404-) promoted photocatalytic activities.

Break-induced replication orchestrates resection-dependent template switching.

Break-induced telomere synthesis (BITS) is a RAD51-independent form of break-induced replication that contributes to alternative lengthening of telomeres1,2. This homology-directed repair mechanism utilizes a minimal replisome comprising proliferating cell nuclear antigen (PCNA) and DNA polymerase-δ to execute conservative DNA repair synthesis over many kilobases. How this long-tract homologous recombination repair synthesis responds to complex secondary DNA structures that elicit replication stress remains unclear3-5. Moreover, whether the break-induced replisome orchestrates additional DNA repair events to ensure processivity is also unclear. Here we combine synchronous double-strand break induction with proteomics of isolated chromatin segments (PICh) to capture the telomeric DNA damage response proteome during BITS1,6. This approach revealed a replication stress-dominated response, highlighted by repair synthesis-driven DNA damage tolerance signalling through RAD18-dependent PCNA ubiquitination. Furthermore, the SNM1A nuclease was identified as the major effector of ubiquitinated PCNA-dependent DNA damage tolerance. SNM1A recognizes the ubiquitin-modified break-induced replisome at damaged telomeres, and this directs its nuclease activity to promote resection. These findings show that break-induced replication orchestrates resection-dependent lesion bypass, with SNM1A nuclease activity serving as a critical effector of ubiquitinated PCNA-directed recombination in mammalian cells.

Accelerating electrochemical CO2 reduction to multi-carbon products via asymmetric intermediate binding at confined nanointerfaces.

Electrochemical CO2 reduction (CO2R) to ethylene and ethanol enables the long-term storage of renewable electricity in valuable multi-carbon (C2+) chemicals. However, carbon-carbon (C-C) coupling, the rate-determining step in CO2R to C2+ conversion, has low efficiency and poor stability, especially in acid conditions. Here we find that, through alloying strategies, neighbouring binary sites enable asymmetric CO binding energies to promote CO2-to-C2+ electroreduction beyond the scaling-relation-determined activity limits on single-metal surfaces. We fabricate experimentally a series of Zn incorporated Cu catalysts that show increased asymmetric CO* binding and surface CO* coverage for fast C-C coupling and the consequent hydrogenation under electrochemical reduction conditions. Further optimization of the reaction environment at nanointerfaces suppresses hydrogen evolution and improves CO2 utilization under acidic conditions. We achieve, as a result, a high 31 ± 2% single-pass CO2-to-C2+ yield in a mild-acid pH 4 electrolyte with >80% single-pass CO2 utilization efficiency. In a single CO2R flow cell electrolyzer, we realize a combined performance of 91 ± 2% C2+ Faradaic efficiency with notable 73 ± 2% ethylene Faradaic efficiency, 31 ± 2% full-cell C2+ energy efficiency, and 24 ± 1% single-pass CO2 conversion at a commercially relevant current density of 150 mA cm-2 over 150 h.

Scalable synthesis of BiVO4 thin films via anodic plating and thermal calcination.

Fabrication of high-quality semiconductor thin films has long been a subject of keen interest in the photocatalytic field. Here, we report a facile, solution-based anodic plating and calcination for large-scale synthesis of BiVO4 thin films on indium tin oxide coated glass for use as photoanodes in solar water splitting. Using Na2SO3 as a sacrificial reagent, continuous solar H2 production with 94% Faradaic efficiency was obtained over 6 h of photoelectrochemical water splitting.

Promoted Photothermal Catalytic CO Hydrogenation by Using TiC-Supported Co-Fe5 C2 Catalysts.

Photothermal catalytic CO hydrogenation offers the potential to synthesize light hydrocarbons by using solar energy. However, the selectivity and activity of the reaction are still far below those achieved in conventional thermal catalytic processes. Herein, we report that the Co-modified Fe5 C2 on TiC catalyst promotes photothermal catalytic CO hydrogenation with a 59 % C2+ selectivity in the produced hydrocarbons and a 30 % single-pass CO conversion at a high gas hourly space-time velocity of 12 000 mL g-1 h-1 . Using in-situ-irradiated XPS, we show that light-induced hot electron injection from TiC to Fe5 C2 modulates the chemical state of Fe, thereby increasing the CO-to-C2+ conversion. This work suggests that it is possible for plasmon-mediated surface chemistry to enhance the activity and selectivity of photothermal catalytic reactions.

Photoredox C-H functionalization leads the site-selective phenylalanine bioconjugation.

Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.

Amide proton transfer magnetic resonance imaging to evaluate renal impairment in patients with chronic kidney disease.

OBJECTIVE: We aimed to investigate the value of amide proton transfer magnetic resonance imaging (APT-MRI) in the classification of chronic kidney disease (CKD). MATERIALS AND METHODS: A total of 30 patients with chronic kidney disease (CKD) and 25 healthy volunteers were enrolled in this study. Patients with chronic kidney disease were divided into two groups according to glomerular filtration rates: mild and moderate-to-severe renal impairment. Differences in cortical and medullary APT values were compared, and the correlation between corticomedullary APT values and glomerular filtration rates was analyzed. Data were statistically analyzed using SPSS 23.0. RESULTS: Based on glomerular filtration rates, 14 patients were assigned to the mild renal impairment group, and 16 were assigned to the moderate-to-severe renal impairment group. Both of the cortical and medullary APT values showed a gradually increasing trend in the control, the mild, and the moderate-to-severe renal impairment groups. Cortical APT values were higher than medullary APT values in all the control and renal impairment groups (P < 0.05). APT values of the right renal cortex (r = -0.80, P < 0.05) and medulla (r = -0.83, P < 0.05) were negatively correlated with the glomerular filtration rate. Results of the receiver operating characteristic (ROC) curve analysis showed that corticomedullary APT values had high diagnostic efficacy in assessing different degrees of renal impairment. CONCLUSIONS: The APT values of the cortex and medulla in patients with CKD gradually increased with disease progression. These findings indicated that APT imaging can be used to evaluate renal function and renal injury in patients with CKD.

Stable, active CO2 reduction to formate via redox-modulated stabilization of active sites.

Electrochemical reduction of CO2 (CO2R) to formic acid upgrades waste CO2; however, up to now, chemical and structural changes to the electrocatalyst have often led to the deterioration of performance over time. Here, we find that alloying p-block elements with differing electronegativities modulates the redox potential of active sites and stabilizes them throughout extended CO2R operation. Active Sn-Bi/SnO2 surfaces formed in situ on homogeneously alloyed Bi0.1Sn crystals stabilize the CO2R-to-formate pathway over 2400 h (100 days) of continuous operation at a current density of 100 mA cm-2. This performance is accompanied by a Faradaic efficiency of 95% and an overpotential of ~ -0.65 V. Operating experimental studies as well as computational investigations show that the stabilized active sites offer near-optimal binding energy to the key formate intermediate *OCHO. Using a cation-exchange membrane electrode assembly device, we demonstrate the stable production of concentrated HCOO- solution (3.4 molar, 15 wt%) over 100 h.

Morning for Irofulven, What Could be fiNER?

Cancers with DNA repair dysfunction are vulnerable to DNA-damaging agents that invoke a requirement for the disabled repair mechanism. Genome sequencing, coupled with a detailed understanding of mechanisms of DNA repair, has accelerated the discovery of pathway-selective agents that target DNA repair deficiencies in a tumor tissue agnostic manner.See related articles by Topka et al., p. 1997 and Börcsök et al., p. 2011.

Copper Sulfide Nanodisk-Doped Solid-Solid Phase Change Materials for Full Spectrum Solar-Thermal Energy Harvesting and Storage.

Phase change materials (PCMs) provide a state-of-the-art thermal energy storage capability and offer enormous potential for solar energy storage systems. However, the widespread adaptation of PCMs in advanced energy systems is often limited by low energy harvesting efficiency and poor shape stability. Thus, developing shape-stable PCMs for high-efficiency solar-thermal energy storage has remained an impediment to further advancement. Herein, we devised novel shape-stable composite PCMs based on monodispersed CuS disk-like nanoparticles and solid-solid PCM polyurethane (PU). In our devised composite system, the incorporated CuS nanoparticles act as a photonic nanoheater and the PU matrix acts as the heat reservoir which can store thermal energy via the latent heat while the phase transition occurs. The fabricated CuS@PU composite with 4 wt % doping of CuS nanodisks exhibits a phase change enthalpy of around 120 J/g, which is only 14% lower than that of the neat PU PCM. Owing to the solid-state phase transition of the PU PCM, only 0.6% of energy storage loss occurred over 100 repeated heating and cooling cycles. Besides, the solar-thermal energy storage efficiency of the CuS@PU composite exceeds 92% at 1 sun illumination under the full solar spectrum. Based on these outstanding thermophysical properties such as excellent shape stability, thermal stability, and thermal reliability, the developed CuS@PU composite PCMs are imperative candidates for real-world applications.

Green light active photocatalyst for complete oxidation of organic molecules.

Photocatalytic organic decomposition is an effective method to combat environmental pollution, a growing public health concern worldwide. Here we report that Fe(iii) nanocluster grafted BiVO4 shows high activity for complete decomposition of organic molecules even under green light. This study is the first investigation to utilize green light for complete gas phase organic decomposition.

Strongly enhanced efficiency of polymer solar cells through unzipped SWNT hybridization in the hole transport layer.

Single-walled carbon nanotubes (SWNTs) have good conductivity, but their size can't match the heterojunction nanostructure in polymer solar cells (PSCs). To improve the photovoltaic performance of PSCs, herein, a faciley fabricated composite hole transport layer composed of unzipped single-walled carbon nanotubes (uSWNTs) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is effectively applied for PSC devices. Compared with the pure PEDOT:PSS hole transport layer (HTL) without uSWNTs, the uSWNTs/PEDOT:PSS layer shows more effective performance as the hole transportation layer. Optimizing the uSWNT concentration in PEDOT:PSS results in fabrication of the PSC devices with uSWNTs/PEDOT:PSS hole transport layers that exhibit greatly improved average power conversion efficiency (PCE), from 13.72% to 14.60%, and greatly enhanced current density and fill factor, which can be ascribed to the increased conductivity and hole transport efficiency. Our approach also supports simple solution-processing techniques and the insensitivity of the performance to thickness, which promises that the faciley fabricated uSWNTs/PEDOT:PSS layer has more potential to be applicable to the roll-to-roll process of PSC fabrication with extremely low cost.

Synergistic photothermal and photochemical partial oxidation of methane over noble metals incorporated in mesoporous silica.

A hot-carrier-driven photocatalytic system was established by incorporating noble metals (Rh, Pd, Ru, and Pt) in a mesoporous silica (MCM-41) for the partial oxidation of methane (POM) under ultraviolet (UV) irradiation. The Rh/MCM photocatalyst initiated POM at a mild operating temperature of 423 K with syngas generation. The reaction was identified as a synergistic photothermal and photochemical process.

Ccr4-Not maintains genomic integrity by controlling the ubiquitylation and degradation of arrested RNAPII.

The Ccr4-Not complex regulates essentially every aspect of gene expression, from mRNA synthesis to protein destruction. The Not4 subunit of the complex contains an E3 RING domain and targets proteins for ubiquitin-dependent proteolysis. Ccr4-Not associates with elongating RNA polymerase II (RNAPII), which raises the possibility that it controls the degradation of elongation complex components. Here, we demonstrate that Ccr4-Not controls the ubiquitylation and turnover of Rpb1, the largest subunit of RNAPII, during transcription arrest. Deleting NOT4 or mutating its RING domain strongly reduced the DNA damage-dependent ubiquitylation and destruction of Rpb1. Surprisingly, in vitro ubiquitylation assays indicate that Ccr4-Not does not directly ubiquitylate Rpb1 but instead promotes Rpb1 ubiquitylation by the HECT domain-containing ligase Rsp5. Genetic analyses suggest that Ccr4-Not acts upstream of RSP5, where it acts to initiate the destruction process. Ccr4-Not binds Rsp5 and forms a ternary complex with it and the RNAPII elongation complex. Analysis of mutant Ccr4-Not lacking the RING domain of Not4 suggests that it both recruits Rsp5 and delivers the E2 Ubc4/5 to RNAPII. Our work reveals a previously unknown function of Ccr4-Not and identifies an essential new regulator of RNAPII turnover during genotoxic stress.

Strong Wet Adhesion of Tough Transparent Nanocomposite Hydrogels for Fast Tunable Focus Lenses.

Tough hydrogel adhesives that can bond strongly to wet surfaces have shown great potential in various applications. However, it still remains a challenge to develop the adhered hydrogels integrated with strong wet adhesion, high transparency, exceptional mechanical properties, and fast self-recovery. Herein, tough nanocomposite hydrogels demonstrating high tensile strength, high transparency, and fast self-recovery are reported. The strong wet adhesion between two tough hydrogel films can be realized by introducing chemical bridging across the hydrogel-hydrogel interface, while the interfacial adhesion energy and shearing adhesion strength are up to 2216 J m-2 and 385 N m-1, respectively. The strong adhesion and superior toughness of our hydrogels enable their reassembly capability to produce stretchable sealed balloons that can endure high air pressure without leakage. Most interestingly, the combination of excellent sealability and high transparency also allows our hydrogel balloons to turn into hydraulically driven fast tunable focus convex lenses, which is first reported here for hydrogel lenses. The hydrogel adhesives may open up the door to develop soft sealed containers and intelligent optical devices.

Highly Stretchable Room-Temperature Self-Healing Conductors Based on Wrinkled Graphene Films for Flexible Electronics.

Flexible conductors are emerging soft materials for diverse electrical applications. However, it still remains a great challenge to fabricate high-performance soft conductors that are highly conductive, largely stretchable, and rapid room-temperature self-healable. Here, we design and fabricate flexible conductive bilayer composite films composed of healable elastomeric substrates and wrinkled graphenes. The elastomeric substrates, obtained by a facile bulk copolymerization of N-isopropylacrylamide and 2-methoxyethyl acrylate, show fast room-temperature self-healing efficiency of up to 96%, imparted by the reversible hydrogen bonds. Importantly, the substrates also display strong interfacial adhesion crucial to the formation of stable bilayer composite films based on a prestrain route. The synergy between self-healing of the substrates and wrinkled structures of graphene is endowed to the composite films for mechanical and electrical healing. By adjusting the prestrain ratio of the substrates, the composite films could display the tunable stretchability, conductivity, and self-healing. The optimal bilayer composite film exhibits a high conductivity of 126 S cm-1, a large stretchability of 300%, and rapid room-temperature self-healing. Moreover, it is demonstrated that the composite films are strain-sensitive and can be used as strain sensors to monitor stretching deformation and human motion. These prominent demonstrations suggest a great potential of the bilayer composite films in next-generation wearable electronics.

Tough and electro-responsive hydrogel actuators with bidirectional bending behavior.

Electro-responsive hydrogel actuators have gained much attention because of their fast response, low power consumption and easy modulation. However, such hydrogel actuators suffer from poor mechanical properties and restricted bending direction, which limit their practical applications. Herein, we report a nanocomposite hydrogel actuator with a combination of high mechanical tensile strength (2 MPa) and automatic bidirectional bending behavior in response to electric signals. The resulting hydrogel, crosslinked by aluminum hydroxide nanoparticles, shows rapid bending behavior and could be cyclically actuated up to ten times in an electric field. Furthermore, the hydrogel demonstrates bidirectional bending actuation, which was ascribed to the difference in diffusion coefficients and concentrations of cations and anions within the gel network. Moreover, the direction and magnitude of the bending behavior could be tuned by composition variation. The hydrogel actuators developed in this study may have great potential in soft robotics, artificial muscles and tissue engineering.

Genome-Wide Mapping of Decay Factor-mRNA Interactions in Yeast Identifies Nutrient-Responsive Transcripts as Targets of the Deadenylase Ccr4.

The Ccr4 (carbon catabolite repression 4)-Not complex is a major regulator of stress responses that controls gene expression at multiple levels, from transcription to mRNA decay. Ccr4, a "core" subunit of the complex, is the main cytoplasmic deadenylase in Saccharomyces cerevisiae; however, its mRNA targets have not been mapped on a genome-wide scale. Here, we describe a genome-wide approach, RNA immunoprecipitation (RIP) high-throughput sequencing (RIP-seq), to identify the RNAs bound to Ccr4, and two proteins that associate with it, Dhh1 and Puf5 All three proteins were preferentially bound to lowly abundant mRNAs, most often at the 3' end of the transcript. Furthermore, Ccr4, Dhh1, and Puf5 are recruited to mRNAs that are targeted by other RNA-binding proteins that promote decay and mRNA transport, and inhibit translation. Although Ccr4-Not regulates mRNA transcription and decay, Ccr4 recruitment to mRNAs correlates better with decay rates, suggesting it imparts greater control over transcript abundance through decay. Ccr4-enriched mRNAs are refractory to control by the other deadenylase complex in yeast, Pan2/3, suggesting a division of labor between these deadenylation complexes. Finally, Ccr4 and Dhh1 associate with mRNAs whose abundance increases during nutrient starvation, and those that fluctuate during metabolic and oxygen consumption cycles, which explains the known genetic connections between these factors and nutrient utilization and stress pathways.

Bio-inspired layered chitosan/graphene oxide nanocomposite hydrogels with high strength and pH-driven shape memory effect.

The layered nanocomposite hydrogel films containing chitosan (CS) and graphene oxide (GO) have been prepared by water evaporation induced self-assembly and subsequent physical cross-linking in alkaline solution. The layered CS/GO hydrogel films obtained have a nacre-like brick-and-mortar microstructure, which contributes to their excellent mechanical properties. The tensile strength and elongation at break of the hydrogel films with 5wt% GO are 5.35MPa and 193.5%, respectively, which are comparable to natural costal cartilage. Furthermore, the CS/GO hydrogel films exhibited pH-driven shape memory effect, and this unique phenomenon is mainly attributed to the reversible transition of partial physically cross-linking corresponding to hydrogen bondings and hydrophobic interactions between CS polymer chains due to pH changing.