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5-Methyl-cytosine (5mC) is one of the most important DNA modifications and plays versatile biological roles. It is well known that 5mC stabilizes DNA duplexes. However, it remains unclear how 5mC affects the kinetics of DNA melting and hybridization. Here, we studied the kinetics of unzipping and rezipping using a 502-bp DNA hairpin by single-molecule magnetic tweezers. Under constant loading rates, 5mC increases the unzipping force but counterintuitively decreases the rezipping force at various salt and temperature conditions. Under constant forces, the non-methylated DNA hops between metastable states during unzipping and rezipping, which implies low energy barriers. Surprisingly, the 5mC DNA can’t rezip after fully unzipping unless much lower forces are applied, where it rezips stochastically in a one-step manner, which implies 5mC kinetically hinders DNA hybridization and high energy barriers in DNA hybridization. All-atom molecular dynamics simulations reveal that the 5mC kinetically hinders DNA hybridization due to steric effects rather than electrostatic effects caused by the additional methyl groups of cytosines. Considering the possible high speed of DNA unzipping and zipping during replication and transcription, our findings provide new insights into the biological roles of 5mC.

Elastomers with outstanding strength, toughness and healing efficiency are highly promising for many emerging fields. However, it is still a challenge to integrate all these beneficial features in one elastomer. Herein, an asymmetric alicyclic structure adjacent to aromatic disulfide was tactfully introduced into the backbone of polyurethane (PU) elastomer. Specifically, such elastomer (PU-HPS) was fabricated by polycondensing polytetramethylene ether glycol (PTMEG), isophorone diisocyanate (IPDI) and p-hydroxydiphenyl disulfide (HPS) via one-pot method. The molecular mobility and phase morphology of PU-HPS can be tuned by adjusting the HPS content. Consequently, the dynamic exchange of hydrogen and disulfide bonds in the hard segment domains can also be tailored. The optimized sample manifests outstanding tensile strength (46.4 MPa), high toughness (109.1 MJ/m3), high self-healing efficiency after fracture (90.3%), complete scratch recovery (100%) and good puncture resistance. Therefore, this work provides a facile strategy for developing robust self-healing polymers.

The use of alkylarenes as nucleophile precursors in benzylic addition is challenging because the benzylic hydrogen atoms of these compounds are inert to deprotonation. Herein, we report Rh-catalyzed benzylic addition of alkylarenes to Michael acceptors for the formation of C(sp

I-motifs are four-strand noncanonical secondary structures formed by cytosine (C)-rich sequences in living cells. The structural dynamics of i-motifs play essential roles in many cellular processes, such as telomerase inhibition, DNA replication, and transcriptional regulation. In cells, the structural dynamics of the i-motif can be modulated by the interaction of poly(C)-binding proteins (PCBPs), and the interaction is closely related to human health, through modulating the transcription of oncogenes and telomere stability. Therefore, the mechanisms of how PCBPs interact with i-motif structures are fundamentally important. However, the underlying mechanisms remain elusive. I-motif structures in the promoter of the c-MYC oncogene can be unfolded by heterogeneous nuclear ribonucleoprotein K (hnRNP K), a PCBP, to activate its transcription. Here, we selected this system as an example to comprehensively study the unfolding mechanisms. We found that the promoter sequence containing 5 C-runs preferred folding into type-1245 to type-1234 i-motif structures based on their folding stability, which was further confirmed by single-molecule FRET. In addition, we first revealed that the c-MYC i-motif structure was discretely resolved by hnRNP K through two intermediate states, which were assigned to the opposite hairpin and neighboring hairpin, as further confirmed by site mutations. Furthermore, we found all three KH (hnRNP K homology) domains of hnRNP K could unfold the c-MYC i-motif structure, and KH2 and KH3 were more active than KH1. In conclusion, this study may deepen our understanding of the interactions between i-motifs and PCBPs and may be helpful for drug development.

Single-stranded guanine-rich RNA sequences have a propensity to fold into compact G-quadruplexes (RG4s). The conformational transitions of these molecules provide an important way to regulate their biological functions. Here, we examined the stability and conformation of an RG4-forming sequence identified near the end of human telomerase RNA. We found that a proximal single-stranded (ss) RNA significantly impairs RG4 stability at physiological K+ concentrations, resulting in a reduced RG4 rupture force of ∼ 24.4 pN and easier accessibility of the G-rich sequence. The destabilizing effect requires a minimum of six nucleotides of ssRNA and is effective at either end of RG4. Remarkably, this RG4-forming sequence, under the influence of such a proximal ssRNA, exhibits interconversions between at least three less stable RG4 conformers that might represent potential intermediates along its folding/unfolding pathway. This work provides insights into the stability and folding dynamics of RG4 that are essential for understanding its biological functions.

RecD family helicases play an important role in prokaryotic genome stability and serve as the structural models for studying superfamily 1B (SF1B) helicases. However, RecD-catalyzed duplex DNA unwinding behavior and the underlying mechanism are still elusive. RecD family helicases share a common proto-helicase with eukaryotic Pif1 family helicases, which are well known for their outstanding G-quadruplex (G4) unwinding ability. However, there are still controversial points as to whether and how RecD helicases unfold G4 structures. Here, single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) were used to study Deinococcus radiodurans RecD2 (DrRecD2)-mediated duplex DNA unwinding and resolution of G4 structures. A symmetric, repetitive unwinding phenomenon was observed on duplex DNA, revealed from the strand switch and translocation of one monomer. Furthermore, we found that DrRecD2 was able to unwind both parallel and antiparallel G4 structures without obvious topological preferences. Surprisingly, the unwinding properties of RecD on duplex and G4 DNA are different from those of Pif1. The findings provide an example, in which the patterns of two molecules derived from a common ancestor deviate during evolution, and they are of significance for understanding the unwinding mechanism and function of SF1B helicases.

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)(3)]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

RNA G-quadruplexes (rG4s) are noncanonical RNA secondary structures formed by guanine (G)-rich sequences. These complexes play important regulatory roles in both animals and plants through their structural dynamics and are closely related to human diseases and plant growth, development, and adaption. Thus, studying the structural dynamics of rG4s is fundamentally important; however, their folding pathways and their unfolding by specialized helicases are not well understood. In addition, no plant rG4-specialized helicases have been identified. Here, using single-molecule FRET, we experimentally elucidated for the first time the folding pathway and intermediates, including a G-hairpin and G-triplex. In addition, using proteomics screening and microscale thermophoresis, we identified and validated five rG4-specialized helicases in Arabidopsis thaliana. Furthermore, DExH1, the ortholog of the famous human rG4 helicase RHAU/DHX36, stood out for its robust rG4 unwinding ability. Taken together, these results shed light on the structural dynamics of plant rG4s.

Given the wide prevalence and ready availability of both phenols and amines, aniline synthesis through direct coupling between these starting materials would be extremely attractive. Herein, we describe a rhodium-catalyzed amination of phenols, which provides concise access to diverse anilines, with water as the sole byproduct. The arenophilic rhodium catalyst facilitates the inherently difficult keto-enol tautomerization of phenols by means of π-coordination, allowing for the subsequent dehydrative condensation with amines. We demonstrate the generality of this redox-neutral catalysis by carrying out reactions of a large array of phenols with various electronic properties and a wide variety of primary and secondary amines. Several examples of late-stage functionalization of structurally complex bioactive molecules, including pharmaceuticals, further illustrate the potential broad utility of the method.

We report a convenient method for benzylic H/D exchange of a wide variety of substrates bearing primary, secondary, or tertiary C-H bonds via a reversible η

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of RTT105 causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.

Brønsted acids of anionic chiral Co(III) complexes were found to act as efficient phase-transfer catalysts for the diastereoselective iodoglycosylation or iodocarboxylation of glycals with a variety of alcohols or carboxylic acids, respectively, with N-iodosuccinimide as the iodo cation source. The corresponding 2-deoxy-2-iodoglycosides, including monosaccharides and disaccharides, and 2-deoxy-2-iodoglycosyl carboxylates, which are of high synthetic and biological importance, were obtained in high yields (up to 88%) with good diastereoselectivities (up to 9:1 dr).

S-DNA (stretched DNA) is an elongated base-paired DNA conformation under high tension. Because the RecA/Rad51 family DNA recombinases form helical filaments on DNA and mediate the formation of the DNA triplex (D-loop), in which the DNA is stretched, and because the extension of these nucleoprotein filaments is similar to the extension of S-DNA, S-DNA has long been hypothesized as a possible state of DNA that participants in RecA/Rad51-mediated DNA strand exchange in homologous recombination. Such a hypothesis, however, is still lacking direct experimental studies. In this work, we have studied the polymerization and strand exchange on S-DNA mediated by Escherichia coli RecA, human Rad51, and Saccharomyces cerevisiae Rad51 by single-molecule magnetic tweezers. We report that RecA/Rad51 polymerizes faster on S-DNA than on B-DNA with the same buffer conditions. Furthermore, the RecA/Rad51-mediated DNA triplex forms faster from S-DNA than from B-DNA together with the homologous single-stranded DNA. These results provide evidence that S-DNA can interact with RecA and Rad51 and shed light on the possible functions of S-DNA.

Single-molecule imaging is emerging as a revolutionary approach to studying fundamental questions in plants. However, compared with its use in animals, the application of single-molecule imaging in plants is still underexplored. Here, we review the applications, advantages, and challenges of single-molecule fluorescence imaging in plant systems from the perspective of methodology. Firstly, we provide a general overview of single-molecule imaging methods and their principles. Next, we summarize the unprecedented quantitative details that can be obtained using single-molecule techniques compared to bulk assays. Finally, we discuss the main problems encountered at this stage and provide possible solutions.

International audience; G-Quadruplexes (G4s) are thermodynamically stable, compact, and poorly hydrated structures that pose a potent obstacle for chromosome replication and gene expression, and requiring resolution by helicases in a cell. Bulk stopped-flow fluorescence assays have provided many mechanistic insights into helicase-mediated duplex DNA unwinding. However, to date, detailed studies on intramolecular G-quadruplexes similar or comparable with those used for studying duplex DNA are still lacking. Here, we describe a method for the direct and quantitative measurement of helicase-mediated intramolecular G-quadruplex unfolding in real time. We designed a series of site-specific fluorescently double-labeled intramolecular G4s and screened appropriate substrates to characterize the helicase-mediated G4 unfolding. With the developed method, we determined, for the first time to our best knowledge, the unfolding and refolding constant of G4 (≈ 5 s −1), and other relative parameters under single-turnover experimental conditions in the presence of G4 traps. Our approach not only provides a new paradigm for characterizing helicasemediated intramolecular G4 unfolding using stopped-flow assays but also offers a way to screen for inhibitors of G4 unfolding helicases as therapeutic drug targets.

Developing degradable and self-healable elastomers composed of reusable resources is of great value, but is rarely reported due to the undegradable molecular chains. Herein, we report a class of degradable and self-healable vitrimers based on non-isocyanate polyurethane elastomer. Such vitrimers are fabricated by copolymerizing bis(6-membered cyclic carbonate) and amino-terminated liquid nitrile rubber (ATBN). The networks topologies can rearrange by transcarbonation exchange reactions between hydroxyl and carbonate groups at elevated temperatures; as such vitrimers after reprocessing can recover 82.9-95.6 % of initial tensile strength and 59−131 % of initial storage modulus. Interestingly, the networks can be hydrolyzed and decarbonated in the strong acid solution to recover 75 % of the pure di(trimethylolpropane) monomer. Additionally, the elastomer exhibits excellent self-healing efficiency (~88 %) and fracture strain (~1200 %) by tuning the monomer feeding ratio. Therefore, this work provides a novel strategy to fabricate the sustainable elastomers with minimum environmental impact.

Purpose: Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the “last resort” choices of CRO infections. We explored the possible factors affecting PMB efficacy. Methods: This retrospective study involved CRO infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had “clinical success” (CS) and “clinical failure” (CF).Results: A total of 192 patients were enrolled: 110 in the CS group and 82 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700–1443.75) vs. 800 (500–1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8–14) vs. 8 (6–11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently.Conclusion: PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose，duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

The chiral Co(III)-complex-templated Bronsted acids were used as efficient bifunctional phase-transfer catalysts for the asymmetric intermolecular iodoacetalization of enol ethers, such as 3,4-dihydro-2H-pyran, 2,3-dihydrofuran, ethyl vinyl ether with alcohols and NIS, furnishing the 3-iodoacetals in high yield with up to 83:17 er.

International audience; The Saccharomyces cerevisiae Pif1 protein (ScPif1p) is the prototypical member of the Pif1 family of DNA helicases. ScPif1p is involved in the maintenance of mitochondrial, ribosomal and telomeric DNA and suppresses genome instability at G-quadruplex motifs. Here, we report the crystal structures of a truncated ScPif1p (ScPif1p237−780) in complex with different ssDNAs. Our results have revealed that a yeast-specific insertion domain protruding from the 2B domain folds as a bundle bearing an α-helix, α16. The α16 helix regulates the helicase activities of ScPif1p through interactions with the previously identified loop3. Furthermore, a biologically relevant dimeric structure has been identified, which can be further specifically stabilized by G-quadruplex DNA. Basing on structural analyses and mutational studies with DNA binding and unwinding assays, a potential G-quadruplex DNA binding site in ScPif1p monomers is suggested. Our results also show that ScPif1p uses the Q-motif to preferentially hydrolyze ATP, and a G-rich tract is preferentially recognized by more residues, consistent with previous biochemical observations. These findings provide a structural and mechanistic basis for understanding the multifunctional ScPif1p.

Guanine (G) quadruplexes (G4s) can be formed by G-rich sequences when stabilized by the binding of cations (typically K+ or Na+) and play an essential role in replication, recombination, transcription, and telomere maintenance. Understanding of the G4 folding process is crucial for determining their cellular functions. However, G4-K+ interactions and folding pathways are still not well understood. By using human telomeric G4 (hTG4) as an example, two binding states corresponding to two K+ cations binding to hTG4 were distinguished clearly and fitted precisely. The basic binding parameters during G4-K+ interactions were measured and calculated by taking advantage of microscale thermophoresis (MST), which monitors the changes in charge and size at the same time. The G-hairpin and G-triplex have been suggested as intermediates during G4 folding and unfolding. We further analyzed the equilibrium dissociation constants of 10 possible folding intermediates using MST; thus, the energetically favorable folding/unfolding pathways were proposed. The results might not only shed new light on G4-K+ interactions and G4 folding pathways but also provide an example for experimentally studying DNA-ion interactions.

Despite having a great variety of topologies, most DNA, RNA, and RNA-DNA hybrid (RDH) configurations for single-molecule manipulation are composed of several single-stranded (ss) DNA and ssRNA strands, with functional labels at the two ends for surface tethering. On this basis, we developed a simple, robust, and universal amplification-annealing (AA) assay for making all these configurations in two or three steps without inefficient digestion and ligation reactions. As examples, we made ssDNA, short ssDNA with double-stranded (ds) DNA handles, dsDNA with ssDNA handles, replication-fork shaped DNA/RDH/RNA, DNA holiday junction, three-site multiple-labeled and nicked DNA, torsion-constrained RNA/RDH, and short ssRNA with RDH handles. In addition to single-molecule manipulation techniques including optical tweezers, magnetic tweezers, and atomic force microscopy, these configurations can be applied in other surface-tethering techniques as well.

Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3′-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.

G-quadruplex (G4) can be formed by G-rich DNA sequences that are widely distributed throughout the human genome. Although G-triplex and G-hairpin have been proposed as G4 folding intermediates, their formation still requires further investigation by experiments. Here, we employed single-molecule FRET to characterize the folding dynamics of G4 from human telomeric sequence. First, we observed four states during G4 folding initially assigned to be anti-parallel G4, G-triplex, G-hairpin and unfolded ssDNA. Then we constructed putative intra-strand G-triplex, G-hairpin structures and confirmed their existences in both NaCl and KCl. Further studies revealed those structures are going through dynamic transitions between different states and show relatively weak dependence on cations, unlike G4. Based on those results and molecular dynamics simulations, we proposed a multi-pathway folding mechanism for human telomeric G4. The present work may shed new light on our current understanding about the existence and stability of G4 intermediate states.

Werner syndrome is caused by mutations in the WRN gene encoding WRN helicase. A knowledge of WRN helicase's DNA unwinding mechanism in vitro is helpful for predicting its behaviors in vivo, and then understanding their biological functions. In the present study, for deeply understanding the DNA unwinding mechanism of WRN, we comprehensively characterized the DNA unwinding properties of chicken WRN helicase core in details, by taking advantages of single-molecule fluorescence resonance energy transfer (smFRET) method. We showed that WRN exhibits repetitive DNA unwinding and translocation behaviors on different DNA structures, including forked, overhanging and G-quadruplex-containing DNAs with an apparently limited unwinding processivity. It was further revealed that the repetitive behaviors were caused by reciprocating of WRN along the same ssDNA, rather than by complete dissociation from and rebinding to substrates or by strand switching. The present study sheds new light on the mechanism for WRN functioning.

Using the joint area of Asia, the Indian Ocean, and the western Pacific Ocean dataset, two transects were selected at 12oN and 19oN actoss the South China Sea (SCS) and adjacent northwest Pacific. The analysis covered the period from January 1993 to December 2006, investigating the spatial variation in the rate of change of sea temperatures. Results show that for the 12oN transect of the southern SCS and nortwest Pacific Ocean, the rate of temperature change in shallow (

Hydrostatic vertical guideway is the key component of modern CNC equipments which is a common lubrication form of turret. In order to improve the cutting stiffness during processing, the hydrostatic vertical guideway in sliding seat during westbank ram processing. Take count different cutting force to analysis the thickness changing of hydrostatic oil film, and then the relation between cutting force and the thickness of oil film is obtained. Based on FVM, relation model between them is established and the limited condition including cutting force is T=100KN, flow flux of each inlet is 0.52L/min, pump of constant delivery type is applied, film thickness is 0.023mm and oil cavity depth is 2mm is numerical simulated. The Hydrostatic pressure field and film thickness under different condition of hydrostatic vertical guideway is obtained. The relation model between film thickness and custom forces is validated. Whats more, the regularity of cutting force influence that impacted on film thickness is revealed. The study is of vital theoretical significance for the improvement of machining accuracy of numerical control machine and the entire CNC equipment and provides valuable theoretical basis for the design of hydrostatic guide rail in engineering practice.

With the development of e-business market, radio frequency identification (RFID) technology is becoming more and more importance. It is often used to identify object because it can work without manual intervention. Several organizations including EPC global and ISO have been working on the standard of RFID all the time in order to promote it using low-cost tags. In particular, the EPC Class-1 Generation-2 standard was accepted as an international standard by ISO/IEC. However, this standard exists some security vulnerabilities. To resolve these vulnerabilities, some protocols conforming to EPC Class 1 Generation 2 was proposed. In this paper, we show the weaknesses which exist in RFID system’s security protocols conforming to EPC Class-1 Generation-2 and submit a new security protocol suitable to the standard, then validate the whole security performance of the new protocol. The safety performance of the new protocol and existing protocols are also compared in this paper .The result shows that the the new protocol could be used in the low-cost tag because of its high security and low communication complexity.

Recent advances in G-quadruplex (G4) studies have confirmed that G4 structures exist in living cells and may have detrimental effects on various DNA transactions. How helicases resolve G4, however, has just begun to be studied and remains largely unknown. In the present paper, we use single-molecule fluorescence assays to probe Pif1-catalysed unfolding of G4 in a DNA construct resembling an ongoing synthesis of lagging strand stalled by G4. Strikingly, Pif1 unfolds and then halts at the ss/dsDNA junction, followed by rapid reformation of G4 and ‘acrobatic’ re-initiation of unfolding by the same monomer. Thus, Pif1 unfolds single G4 structures repetitively. Furthermore, it is found that Pif1 unfolds G4 sequentially in two large steps. Our study has revealed that, as a stable intermediate, G-triplex (G3) plays an essential role in this process. The repetitive unfolding activity may facilitate Pif1 disrupting the continuously reforming obstructive G4 structures to rescue a stalled replication fork. The proposed mechanism for step-wise unfolding of G4 is probably applicable to other helicases that resolve G4 structures for maintaining genome stability.

To develop gastric floating erodible plug pulse capsules with compound Danshen as the model drug, in order to realize the pulse release of traditional Chinese medicines. Through the study on impermeable capsules, optimized prescriptions, drug-containing rapid-release tablets and prescription screening, and erodible plug prescription and process, we successfully prepared compounded Danshen pulse capsule, so as to provide a new dosage form for controlling and treating heart disease to better cater to clinical demands.

In this paper, small diameter InP nanowires with high crystal quality were synthesized through a chemical vapor deposition method. Benefitting from the high crystallinity and large specific surface area of InP nanowires, the simply constructed photodetector demonstrates a high responsivity of up to 1170 AW−1 and an external quantum efficiency of 2.8×105% with a fast rise time of 110 ms and a fall time of 130 ms, even at low bias of 0.1 V. The effect of back-gate voltage on photoresponse of the device was systematically investigated, confirming that the photocurrent dominates over thermionic and tunneling currents in the whole operation. A mechanism based on energy band theory at the junction between metal and semiconductor was proposed to explain the back-gate voltage dependent performance of the photodetectors. These convincing results indicate that fine InP nanowires will have a brilliant future in smart optoelectronics.