HCovDock: an efficient docking method for modeling covalent protein-ligand interactions.

Covalent inhibitors have received extensive attentions in the past few decades because of their long residence time, high binding efficiency and strong selectivity. Therefore, it is valuable to develop computational tools like molecular docking for modeling of covalent protein-ligand interactions or screening of potential covalent drugs. Meeting the needs, we have proposed HCovDock, an efficient docking algorithm for covalent protein-ligand interactions by integrating a ligand sampling method of incremental construction and a scoring function with covalent bond-based energy. Tested on a benchmark containing 207 diverse protein-ligand complexes, HCovDock exhibits a significantly better performance than seven other state-of-the-art covalent docking programs (AutoDock, Cov_DOX, CovDock, FITTED, GOLD, ICM-Pro and MOE). With the criterion of ligand root-mean-squared distance < 2.0 Å, HCovDock obtains a high success rate of 70.5% and 93.2% in reproducing experimentally observed structures for top 1 and top 10 predictions. In addition, HCovDock is also validated in virtual screening against 10 receptors of three proteins. HCovDock is computationally efficient and the average running time for docking a ligand is only 5 min with as fast as 1 sec for ligands with one rotatable bond and about 18 min for ligands with 23 rotational bonds. HCovDock can be freely assessed at http://huanglab.phys.hust.edu.cn/hcovdock/.

Electrocatalysis of nitrogen pollution: transforming nitrogen waste into high-value chemicals.

On 16 June 2023, the United Nations Environment Programme highlighted the severity of nitrogen pollution faced by humans and called for joint action for sustainable nitrogen use. Excess nitrogenous waste (NW: NO, NO2, NO2-, NO3-, etc.) mainly arises from the use of synthetic fertilisers, wastewater discharge, and fossil fuel combustion. Although the amount of NW produced can be minimised by reducing the use of nitrogen fertilisers and fossil fuels, the necessity to feed seven billion people on Earth limits the utility of this approach. Compared to current industrial processes, electrocatalytic NW reduction or CO2-NW co-reduction offers a potentially greener alternative for recycling NW and producing high-value chemicals. However, upgrading this technology to connect upstream and downstream industrial chains is challenging. This viewpoint focuses on electrocatalytic NW reduction, a cutting-edge technology, and highlights the challenges in its practical application. It also discusses future directions to meet the requirements of upstream and downstream industries by optimising production processes, including the pretreatment and supply of nitrogenous raw materials (e.g. flue gas and sewage), design and macroscopic preparation of electrocatalysts, and upscaling of reactors and other auxiliary equipment.

Atomically Thin Kagome-Structured Co9Te16 Achieved through Self-Intercalation and Its Flat Band Visualization.

Kagome materials have recently garnered substantial attention due to the intrinsic flat band feature and the stimulated magnetic and spin-related many-body physics. In contrast to their bulk counterparts, two-dimensional (2D) kagome materials feature more distinct kagome bands, beneficial for exploring novel quantum phenomena. Herein, we report the direct synthesis of an ultrathin kagome-structured Co-telluride (Co9Te16) via a molecular beam epitaxy (MBE) route and clarify its formation mechanism from the Co-intercalation in the 1T-CoTe2 layers. More significantly, we unveil the flat band states in the ultrathin Co9Te16 and identify the real-space localization of the flat band states by in situ scanning tunneling microscopy/spectroscopy (STM/STS) combined with first-principles calculations. A ferrimagnetic order is also predicted in kagome-Co9Te16. This work should provide a novel route for the direct synthesis of ultrathin kagome materials via a metal self-intercalation route, which should shed light on the exploration of the intriguing flat band physics in the related systems.

Electrolyte Engineering Empowers Li||CFx Batteries to Achieve High Energy Density and Low Self-Discharge at Harsh Conditions.

Given its exceptional theoretical energy density (over 2000 Wh kg-1), lithium||carbon fluoride (Li||CFx) battery has garnered global attention. N-methylpyrrolidone (NMP)-based electrolyte is regarded as one promising candidate for tremendously enhancing the energy density of Li||CFx battery, provided self-discharge challenges can be resolved. This study successfully achieves a low self-discharge (LSD) and desirable electrochemical performance in Li||CFx batteries at high temperatures by utilizing NMP as the solvent and incorporating additional ingredients, including vinylene carbonate additive, as well as the dual-salt systems formed by LiBF4 with three different Li salts, namely lithium bis(oxalato)borate, lithium difluoro(oxalato)borate, and LiNO3. The experimental results unfold that the proposed methods not only minimize aluminum current collector corrosion, but also effectively passivate the Li metal anode. Among them, LiNO3 exhibits the most pronounced effect that achieves an energy density of ≈2400 Wh kg-1 at a current density of 10 mA g-1 at 30 °C, nearly 0% capacity-fade rate after 300 h of storage at 60 °C, and the capability to maintain a stable open-circuit voltage over 4000 h. This work provides a distinctive perspective on how to realize both high energy density and LSD rates at high temperature of Li||CFx battery.

Large-Substrate-Terrace Confined Growth of Arrayed Ultrathin PtSe2 Ribbons on Step-Bunched Vicinal Au(001) Facets Toward Electrocatalytic Applications.

Ultrathin PtSe2 ribbons can host spin-polarized edge states and distinct edge electrocatalytic activity, emerging as a promising candidate for versatile applications in various fields. However, the direct synthesis is still challenging and the growth mechanism is still unclear. Herein, the arrayed growth of ultrathin PtSe2 ribbons on bunched vicinal Au(001) facets, via a facile chemical vapor deposition (CVD) route is reported. The ultrathin PtSe2 flakes can transform from traditional irregular shapes to desired ribbon shapes by increasing the height of bunched and unidirectionally oriented Au steps (with step height hstep) is found. This crossover, occurring at hstep ≈ 3.0 nm, defines the tailored growth from step-flow to single-terrace-confined modes, as validated by density functional theory calculations of the different system energies. On the millimeter-scale single-crystal Au(001) films with aligned steps, the arrayed ultrathin PtSe2 ribbons with tunable width of ≈20-1000 nm, which are then served as prototype electrocatalysts for hydrogen evolution reaction (HER) is achieved. This work should represent a huge leap in the direct synthesis and the mechanism exploration of arrayed ultrathin transition-metal dichalcogenides (TMDCs) ribbons, which should stimulate further explorations of the edge-related physical properties and practical applications.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

Conditional Dynamics in Heterodyne Detection of Superradiant Lasing with Incoherently Pumped Atoms.

In this Letter, we use quantum trajectory theory to simulate heterodyne detection of narrow bandwidth superradiant lasing from an incoherently excited atomic ensemble. To this end, we describe the system dynamics and account for stochastic measurement backaction by second-order mean-field theory. Our simulations show how heterodyne measurements break the phase symmetry, and initiate the atomic coherence with a random phase and a long temporal phase coherence. More importantly, our theory allows direct simulation of experimental procedures for extraction of spectral information which do not lend themselves to evaluation with the quantum regression theorem.

Water-Assisted Growth of Twisted 3R-Stacked MoSe2 Spirals and Its Dramatically Enhanced Second Harmonic Generations.

Enhanced second-harmonic generation (SHG) responses are reported in monolayer transition metal dichalcogenides (e.g., MX2 , M: Mo, W; X: S, Se) due to the broken symmetries. The 3R-like stacked MX2 spiral structures possessing the similar broken inversion symmetry should present dramatically enhanced SHG responses, thus providing great flexibility in designing miniaturized on-chip nonlinear optical devices. To achieve this, the first direct synthesis of twisted 3R-stacked chiral molybdenum diselenide (MoSe2 ) spiral structures with specific screw dislocations (SD) arms is reported, via designing a water-assisted chemical vapor transport (CVT) approach. The study also clarifies the formation mechanism of the MoSe2 spiral structures, by precisely regulating the precursor supply accompanying with multiscale characterizations. Significantly, an up to three orders of magnitude enhancement of the SHG responses in twisted 3R stacked MoSe2 spirals is demonstrated, which is proposed to arise from the synergistic effects of broken inversion symmetry, strong light-matter interaction, and band nesting effects. Briefly, the work provides an efficient synthetic route for achieving the 3R-stacked TMDCs spirals, which can serve as perfect platforms for promoting their applications in on-chip nonlinear optical devices.

Facile and Scalable Mechanochemical Synthesis of Defective MoS2 with Ru Single Atoms Toward High-Current-Density Hydrogen Evolution.

Designing a facile strategy to prepare catalysts with highly active sites are challenging for large-scale implementation of electrochemical hydrogen production. Herein, a straightforward and eco-friendly method by high-energy mechanochemical ball milling for mass production of atomic Ru dispersive in defective MoS2 catalysts (Ru1 @D-MoS2 ) is developed. It is found that single atomic Ru doping induces the generation of S vacancies, which can break the electronic neutrality around Ru atoms, leading to an asymmetrical distribution of electrons. It is also demonstrated that the Ru1 @D-MoS2 exhibits superb alkaline hydrogen evolution enhancement, possibly attributing to this electronic asymmetry. The overpotential required to deliver a current density of 10 mA cm-2 is as low as 107 mV, which is much lower than that of commercial MoS2 (C-MoS2 , 364 mV). Further density functional theory (DFT) calculations also support that the vacancy-coupled single Ru enables much higher electronic distribution asymmetry degree, which could regulate the adsorption energy of intermediates, favoring the water dissociation and the adsorption/desorption of H*. Besides, the long-term stability test under 500 mA cm-2 further confirms the robust performance of Ru1 @D-MoS2 . Our strategy provides a promising and practical way towards large-scale preparation of advanced HER catalysts for commercial applications.

Assessment of Right Ventricular-Arterial Coupling by Echocardiography in Patients with Right Ventricular Pressure and Volume Overload.

Background: Right ventricle-pulmonary arterial (RV-PA) coupling is considered the gold standard for assessing right ventricular (RV) function and can be evaluated noninvasively by echocardiography. The ratios of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP), RV global longitudinal strain (G-RVLS)/PASP, and stroke volume/end-systolic volume (SV/ESV) have been proposed as surrogates of RV-PA coupling. The relationship of these parameters remains incompletely understood in patients with volume and pressure loading conditions. We aimed to compare these parameters and evaluate their relationship with 3D RV data in patients with RV pressure and volume overload. Methods: This study was performed on 110 individuals who underwent 2D and 3D echocardiography. Fifty-four patients had RV volume overload (atrial septal defect (ASD) group), 34 patients had RV pressure overload (pulmonary hypertension (PH) group), and 22 were controls. TAPSE/PASP, G-RVLS/PASP and SV/ESV ratios were calculated. Correlations between parameters of RV-PA coupling and 3D data were assessed using general linear mixed models. Results: Compared with the ASD group, the PH group had lower TAPSE/PASP and G-RVLS/PASP ratios. The SV/ESV ratio had a strong correlation with right ventricle ejection fraction (RVEF) in both ASD and PH patients (r = 0.8703, p < 0.001 and r = 0.9388, p < 0.001, respectively). The G-RVLS/PASP ratio showed a strong or moderately negative relationship with end-diastolic volume (EDV), ESV and SV (r = -0.7768, p = 0.001; r = -0.7327, p = 0.0005 and r = -0.6816, p = 0.0018, respectively) in PH patients. The TAPSE/PASP ratio showed moderately negative correlations with EDV and ESV (r = -0.5712, p = 0.0012 and r = -0.5594, p = 0.0016, respectively) in PH patients. Conclusions: Non-invasive RV-PA coupling parameters derived from echocardiography appear similar, but not identical to profiles in pressure-overloaded and volume-overloaded patients. The correlations between non-invasive RV-PA coupling parameters and 3D data displayed various degrees of correlation.

Multi-UAV Redeployment Optimization Based on Multi-Agent Deep Reinforcement Learning Oriented to Swarm Performance Restoration.

Distributed artificial intelligence is increasingly being applied to multiple unmanned aerial vehicles (multi-UAVs). This poses challenges to the distributed reconfiguration (DR) required for the optimal redeployment of multi-UAVs in the event of vehicle destruction. This paper presents a multi-agent deep reinforcement learning-based DR strategy (DRS) that optimizes the multi-UAV group redeployment in terms of swarm performance. To generate a two-layer DRS between multiple groups and a single group, a multi-agent deep reinforcement learning framework is developed in which a QMIX network determines the swarm redeployment, and each deep Q-network determines the single-group redeployment. The proposed method is simulated using Python and a case study demonstrates its effectiveness as a high-quality DRS for large-scale scenarios.

SMALL PLANT AND ORGAN 1 (SPO1) Encoding a Cellulose Synthase-like Protein D4 (OsCSLD4) Is an Important Regulator for Plant Architecture and Organ Size in Rice.

Plant architecture and organ size are considered as important traits in crop breeding and germplasm improvement. Although several factors affecting plant architecture and organ size have been identified in rice, the genetic and regulatory mechanisms remain to be elucidated. Here, we identified and characterized the small plant and organ 1 (spo1) mutant in rice (Oryza sativa), which exhibits narrow and rolled leaf, reductions in plant height, root length, and grain width, and other morphological defects. Map-based cloning revealed that SPO1 is allelic with OsCSLD4, a gene encoding the cellulose synthase-like protein D4, and is highly expressed in the roots at the seedling and tillering stages. Microscopic observation revealed the spo1 mutant had reduced number and width in leaf veins, smaller size of leaf bulliform cells, reduced cell length and cell area in the culm, and decreased width of epidermal cells in the outer glume of the grain. These results indicate the role of SPO1 in modulating cell division and cell expansion, which modulates plant architecture and organ size. It is showed that the contents of endogenous hormones including auxin, abscisic acid, gibberellin, and zeatin tested in the spo1 mutant were significantly altered, compared to the wild type. Furthermore, the transcriptome analysis revealed that the differentially expressed genes (DEGs) are significantly enriched in the pathways associated with plant hormone signal transduction, cell cycle progression, and cell wall formation. These results indicated that the loss of SPO1/OsCSLD4 function disrupted cell wall cellulose synthase and hormones homeostasis and signaling, thus leading to smaller plant and organ size in spo1. Taken together, we suggest the functional role of SPO1/OsCSLD4 in the control of rice plant and organ size by modulating cell division and expansion, likely through the effects of multiple hormonal pathways on cell wall formation.

A Janus Separator based on Cation Exchange Resin and Fe Nanoparticles-decorated Single-wall Carbon Nanotubes with Triply Synergistic Effects for High-areal Capacity Zn-I2 Batteries.

Zn-I2 batteries stand out in the family of aqueous Zn-metal batteries (AZMBs) due to their low-cost and immanent safety. However, Zn dendrite growth, polyiodide shuttle effect and sluggish I2 redox kinetics result in dramatically capacity decay of Zn-I2 batteries. Herein, a Janus separator composed of functional layers on anode/cathode sides is designed to resolve these issues simultaneously. The cathode layer of Fe nanoparticles-decorated single-wall carbon nanotubes can effectively anchor polyiodide and catalyze the redox kinetics of iodine species, while the anode layer of cation exchange resin rich in -SO3 - groups is beneficial to attract Zn2+ ions and repel detrimental SO4 2- /polyiodide, improving the stability of cathode/anode interfaces synergistically. Consequently, the Janus separator endows outstanding cycling stability of symmetrical cells and high-areal-capacity Zn-I2 batteries with a lifespan over 2500 h and a high-areal capacity of 3.6 mAh cm-2 .

Single Carbon Vacancy Traps Atomic Platinum for Hydrogen Evolution Catalysis.

The coordinated configuration of atomic platinum (Pt) has always been identified as an active site with high intrinsic activity for hydrogen evolution reaction (HER). Herein, we purposely synthesize single vacancies in a carbon matrix (defective graphene) that can trap atomic Pt to form the Pt-C3 configuration, which gives exceptionally high reactivity for HER in both acidic and alkaline solutions. The intrinsic activity of Pt-C3 site is valued with a turnover frequency (TOF) of 26.41 s-1 and mass activity of 26.05 A g-1 at 100 mV, respectively, which are both nearly 18 times higher than those of commercial 20 wt % Pt/C. It is revealed that the optimal coordination Pt-C3 has a stronger electron-capture ability and lower Gibbs free energy difference (ΔG), resulting in promoting the reduction of adsorbed H+ and the acceleration of H2 desorption, thus exhibiting the extraordinary HER activity. This work provides a new insight on the unique coordinated configuration of dispersive atomic Pt in defective C matrix for superior HER performance.

Cavity Quantum Electrodynamics Effects with Nitrogen Vacancy Center Spins Coupled to Room Temperature Microwave Resonators.

Cavity quantum electrodynamics (CQED) effects, such as Rabi splitting, Rabi oscillations, and superradiance, have been demonstrated with nitrogen vacancy (NV) center spins in diamond coupled to microwave resonators at cryogenic temperature. In this Letter, we explore the possibility to realize strong collective coupling and CQED effects with ensembles of NV spins at room temperature. Our calculations show that thermal excitation of the individual NV spins leads to population of collective Dicke states with low symmetry and a reduced collective coupling to the microwave resonators. Optical pumping can be applied to counteract the thermal excitation of the NV centers and to prepare the spin ensemble in Dicke states with high symmetry. The resulting strong coupling with high-quality resonators enables the study of intriguing CQED effects across the weak-to-strong coupling regime, and may have applications in quantum sensing and quantum information processing.

Spectroscopic Visualization of Flat Bands in Magic-Angle Twisted Monolayer-Bilayer Graphene: Coexistence of Localization and Delocalization.

Recent transport studies have demonstrated the great potential of twisted monolayer-bilayer graphene (TMBG) as a new platform to host moiré flat bands with a higher tunability than twisted bilayer graphene (TBG). However, a direct visualization of the flat bands in TMBG and its comparison with the ones in TBG remain unexplored. Here, via fabricating on a single sample with exactly the same twist angle of ∼1.13°, we present a direct comparative study between TMBG and TBG using scanning tunneling microscopy and spectroscopy. We observe a sharp density of states peak near the Fermi energy in tunneling spectroscopy, confirming unambiguously the existence of flat electronic bands in TMBG. The bandwidth of this flat-band peak is found to be slightly narrower than that of the TBG, validating previous theoretical predictions. Remarkably, by measuring spatially resolved spectroscopy, combined with continuum model calculation, we show that the flat-band states in TMBG exhibit a unique layer-resolved localization-delocalization coexisting feature, which offers an unprecedented possibility to utilize their cooperation on exploring novel correlation phenomena. Our work provides important microscopic insight of flat-band states for better understanding the emergent physics in graphene moiré systems.

Holo Protein Conformation Generation from Apo Structures by Ligand Binding Site Refinement.

An important part in structure-based drug design is the selection of an appropriate protein structure. It has been revealed that a holo protein structure that contains a well-defined binding site is a much better choice than an apo structure in structure-based drug discovery. Therefore, it is valuable to obtain a holo-like protein conformation from apo structures in the case where no holo structure is available. Meeting the need, we present a robust approach to generate reliable holo-like structures from apo structures by ligand binding site refinement with restraints derived from holo templates with low homology. Our method was tested on a test set of 32 proteins from the DUD-E data set and compared with other approaches. It was shown that our method successfully refined the apo structures toward the corresponding holo conformations for 23 of 32 proteins, reducing the average all-heavy-atom RMSD of binding site residues by 0.48 Å. In addition, when evaluated against all the holo structures in the protein data bank, our method can improve the binding site RMSD for 14 of 19 cases that experience significant conformational changes. Furthermore, our refined structures also demonstrate their advantages over the apo structures in ligand binding mode predictions by both rigid docking and flexible docking and in virtual screening on the database of active and decoy ligands from the DUD-E. These results indicate that our method is effective in recovering holo-like conformations and will be valuable in structure-based drug discovery.

NLDock: a Fast Nucleic Acid-Ligand Docking Algorithm for Modeling RNA/DNA-Ligand Complexes.

Nucleic acid-ligand interactions play an important role in numerous cellular processes such as gene function expression and regulation. Therefore, nucleic acids such as RNAs have become more and more important drug targets, where the structural determination of nucleic acid-ligand complexes is pivotal for understanding their functions and thus developing therapeutic interventions. Molecular docking has been a useful computational tool in predicting the complex structure between molecules. However, although a number of docking algorithms have been developed for protein-ligand interactions, only a few docking programs were presented for nucleic acid-ligand interactions. Here, we have developed a fast nucleic acid-ligand docking algorithm, named NLDock, by implementing our intrinsic scoring function ITScoreNL for nucleic acid-ligand interactions into a modified version of the MDock program. NLDock was extensively evaluated on four test sets and compared with five other state-of-the-art docking algorithms including AutoDock, DOCK 6, rDock, GOLD, and Glide. It was shown that our NLDock algorithm obtained a significantly better performance than the other docking programs in binding mode predictions and achieved the success rates of 73%, 36%, and 32% on the largest test set of 77 complexes for local rigid-, local flexible-, and global flexible-ligand docking, respectively. In addition, our NLDock approach is also computationally efficient and consumed an average of as short as 0.97 and 2.08 min for a local flexible-ligand docking job and a global flexible-ligand docking job, respectively. These results suggest the good performance of our NLDock in both docking accuracy and computational efficiency.

Impacts of sodium hydroxide and sodium hypochlorite aging on polyvinylidene fluoride membranes fabricated with different methods.

This study compared the effects of chemical aging on the polyvinylidene fluoride (PVDF) membranes fabricated with the methods of non-solvent induced phase separation (NIPS) (named NIPS-PVDF) and thermally induced phase separation (TIPS) (named TIPS-PVDF). The chemical solutions of sodium hypochlorite (NaClO) and sodium hydroxide (NaOH) were chosen at the concentration of 5000mg/L. The equivalence of 5 and 10years was respectively selected as the time of aging. The physicochemical evolutions of membrane aging are characterized on the base of morphology analysis, chemical components, permeation ability and mechanical properties. The aging of NIPS-PVDF membrane led to the elimination of surface hydrophilic additives, while NaOH focused on the dehydrofluorination process resulting in the formation of conjugated chains of polyene on the skeleton structure. The chemical components of the surface of TIPS-PVDF membrane were removed continuously during the aging processes of both NaClO and NaOH, which was caused by the saponification of surface additives and the chain scissions of skeleton structure, but without producing any obvious conjugated chains of polyene. All the aging processes led to the increase of contact angle and the decrease of mechanical properties, and the permeability was reduced first and increased later due to the enlargement of surface membrane pores and membrane block. With the influence of membrane aging, selectivity of membrane was decreased (except coliform bacteria). At the beginning of filtration, the turbidity and particle count were at relatively high levels and declined with the filtration process.

A dual-colored ratiometric-fluorescent oligonucleotide probe for the detection of human telomerase RNA in cell extracts.

Human telomerase RNA (hTR), which is one component of telomerase, was deemed to be a biomarker to monitor tumor cells due to its different expression levels in tumor cells and normal somatic cells. Thus far, plentiful fluorescent probes have been designed to investigate nucleic acids. However, most of them are limited since they are time-consuming, require professional operators and even result in false positive signals in the cellular environment. Herein, we report a dual-colored ratiometric-fluorescent oligonucleotide probe to achieve the reliable detection of human telomerase RNA in cell extracts. The probe is constructed using a dual-labeled fluorescent oligonucleotide hybridized with target-complemented Dabcyl-labeled oligonucleotide. In the presence of the target, the dual-labeled fluorescent oligonucleotide translates into a hairpin structure, which leads to the generation of the fluorescence resonance energy transfer (FRET) phenomenon under UV excitation. Compared to conventional methods, this strategy could effectively avoid false positive signals, and it not only possesses the advantages of simplicity and high specificity but also has the merits of signal stability and distinguishable color variation. Moreover, the quantitative assay of hTR would have a far-reaching impact on the telomerase mechanism and even tumor diagnosis research.